NCBI Conserved Domain Search

Neogenin C-terminus; This family represents the C-terminus of eukaryotic neogenin precursor proteins, which contains several potential phosphorylation sites. Neogenin is a member of the N-CAM family of cell adhesion molecules (and therefore contains multiple copies of pfam00047 and pfam00041) and is closely related to the DCC tumour suppressor gene product - these proteins may play an integral role in regulating differentiation programmes and/or cell migration events within many adult and embryonic tissues.

Pssm-ID: 461954 [Multi-domain] Cd Length: 289 Bit Score: 409.30 E-value: 3.50e-132

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1148 LRPPDLWIHHEEMEMKNIEKPTGTDPAGRDSPI-QSCQDLTPVSHSQSETQMGSKSASHSGQDTEDAGSSmstlersLAA 1226
Cdd:pfam06583    1 LKPPDLWIHHEQMELKNIEKSPSPNPSGTDSPIgQSSQDLPPVDHSQSESQIHQKSNSYSGNDSDEKSST-------LAG 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1227 RRATRAKLMIPMEAQSSNPAVVSAIPVPTLESAQ---YPGILPSPTCGYPHPQFTLrpvPFPTLSVDRGFGAGRTQSVSE 1303
Cdd:pfam06583   74 RRGTRPKMMLPMDSQPSNQPVVSAIPIPSLDSSHqyaHPGILPSPTCGYLHNQFSL---PFPGTPVPRSDTAPSAESVEN 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1304 GPTTQQQPMLPPAQPEHP----SSEEAPSRTIPTACVRPTHPLRSFANPLLPPPMSaiepkvPYTPLLSQPGPTLPKTHV 1379
Cdd:pfam06583  151 TPLQSQLPYQPSSQSESGslssAVEEEPNRSIPTAKVRPGHPLKSFSVPAPPPQSA------PSTPLQQQHRPTLSKSPV 224

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  1380 KTASLGLAGKARSPLlPVSVPTAPEVSEESHKPTEDPASVYEQDDLSEQMASLEGLMKQLNAITGS 1445
Cdd:pfam06583  225 KTASLGTAGKARSPL-PVSVPNAPDTSEETERLLEDAAPSYETDELSEEMANLEGLMKDLNAITAS 289

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 187.30 E-value: 2.11e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   39 SLHFVSEPSDAVTMRGGNVLLNCSAESDRgVPVIKWKKDGLILALGMDDRKQQLPNGSLLIQNILHSRHHKPDEGLYQCE 118
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDP-PPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVHSKHNKPDEGFYQCV 79

                          90
                  ....*....|....*...
gi 117168295  119 ASLADSGSIISRTAKVTV 136
Cdd:cd05722    80 AQNESLGSIVSRTARVTV 97

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 176.23 E-value: 9.63e-52

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  334 LNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSA 413
Cdd:cd05723     1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASA 80


                  ....
gi 117168295  414 QLIV 417
Cdd:cd05723    81 QLII 84

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 112.02 E-value: 5.55e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  478 NTTQPGSLQLTVGNLKPEAMYTFRVVAYNEWGPGESSQPIKVATQPELqvPGPVENLHAVSTSPTSILITWEPPayANGP 557
Cdd:COG3401   185 LTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTP--PSAPTGLTATADTPGSVTLSWDPV--TESD 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  558 VQGYRLFCTEVSTGKEQNI-EVDGLSYKLEGLKKFTEYTLRFLAYNRYG-PGVSTDDITVVTLSDVPsAPPQNISLEVVN 635
Cdd:COG3401   261 ATGYRVYRSNSGDGPFTKVaTVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPP-AAPSGLTATAVG 339

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  636 SRSIKVSWlpppSGTQNGFITGYKIrHRKTTRRGEMETL--EPNNLWYLFTGLEKGSQYSFQVSAMTVNGT-GPPSNWYT 712
Cdd:COG3401   340 SSSITLSW----TASSDADVTGYNV-YRSTSGGGTYTKIaeTVTTTSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVS 414

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  713 AETPENDLDES--QVPDQPSSLHVRPQTNCIIMSWTPPLNPNIVVRGYIIGYGV-GSPYAETVRVDSKQRYYSIERLESS 789
Cdd:COG3401   415 ATTASAASGESltASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVpFTTTSSTVTATTTDTTTANLSVTTG 494

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  790 SHYVISLKAFNNAGEGVPLYESATTRSITDPTDPVDYYPLLDDFPTSGPDVSTPMLPPVGVQAVAltheavrvSWADNSV 869
Cdd:COG3401   495 SLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTGDVLITDLVSLTTSASS--------SVSGAGL 566

                         410       420       430
                  ....*....|....*....|....*....|..
gi 117168295  870 PKNQKTSDVRLYTVRWRTSFSASAKYKSEDTT 901
Cdd:COG3401   567 GSGNLYLITTLGGSLLTTTSTNTNDVAGVHGG 598

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 97.00 E-value: 2.95e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  566 TEVSTGKEQNIEVDGLSYKLEGLKKFTEYTLRFLAYNRYGPGVSTDDITVVTLSDVPSApPQNISLEVVNSRSIKVSWLP 645
Cdd:COG3401   177 TAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSA-PTGLTATADTPGSVTLSWDP 255

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  646 PPsgtqNGFITGYKIrHRKTTRRGEMETL-EPNNLWYLFTGLEKGSQYSFQVSAMTVNGT-GPPSNWYTAETpendldES 723
Cdd:COG3401   256 VT----ESDATGYRV-YRSNSGDGPFTKVaTVTTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTT------DL 324

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  724 QVPDQPSSLHVRPQTNCIIM-SWTPPLNPNIVvrGYII--GYGVGSPYaETVRVDSKQRYYSIERLESSSHYVISLKAFN 800
Cdd:COG3401   325 TPPAAPSGLTATAVGSSSITlSWTASSDADVT--GYNVyrSTSGGGTY-TKIAETVTTTSYTDTGLTPGTTYYYKVTAVD 401

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  801 NAGEGVPLYESATTRSITDPTDPVDYYPLLDDFPTSGPDVSTPML----PPVGVQAVALTHEAVRVSWADNSVPKNQKTS 876
Cdd:COG3401   402 AAGNESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASaasnPGVSAAVLADGGDTGNAVPFTTTSSTVTATT 481

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  877 DVRLYTVRWRTSFSASAKYKSEDTTSLSYTATGLKPNTMYEFSVMVTkNRRSSTWSMTAHATTYEAAPTSAPKDLTVITR 956
Cdd:COG3401   482 TDTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTP-NVTGASPVTVGASTGDVLITDLVSLTTSASSS 560

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|.
gi 117168295  957 EGKPRAVIVSWQPPLEANGKITAYILFYTLDKNIPIDDWIM 997
Cdd:COG3401   561 VSGAGLGSGNLYLITTLGGSLLTTTSTNTNDVAGVHGGTLL 601

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 85.39 E-value: 8.26e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   241 YFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQlRSKKYSLL---GGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVTyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 117168295   318 NISASAELTV 327
Cdd:pfam07679   81 EAEASAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 83.46 E-value: 3.63e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIV---GGSNLRILGVVKSDEGFYQCVAENEAG 407
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 117168295   408 NAQSSAQLIV 417
Cdd:pfam07679   81 EAEASAELTV 90

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 82.93 E-value: 5.78e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  528 PGPVENLHAVSTSPTSILITWEPPAYANGPVQGYRLFCTEVSTGKEQNIEV---DGLSYKLEGLKKFTEYTLRFLAYNRY 604
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpgSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 117168295  605 GPGVSTDDITVVT 617
Cdd:cd00063    81 GESPPSESVTVTT 93

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 79.47 E-value: 7.52e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSN---LLISNVTDDDSGTYTCVVTYKNENISAS 322
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 117168295    323 AELTV 327
Cdd:smart00410   81 TTLTV 85

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 89.29 E-value: 7.89e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  397 FYQCVAENEAGNAQSSAQLIVPKPAIPsssilPSAPRDVLPVLVSSRFVRLSWRPPAEAkgNIQTFTVFFSREGDNRERA 476
Cdd:COG3401   206 YYRVAATDTGGESAPSNEVSVTTPTTP-----PSAPTGLTATADTPGSVTLSWDPVTES--DATGYRVYRSNSGDGPFTK 278

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  477 LNTTQpgSLQLTVGNLKPEAMYTFRVVAYNEWG-PGESSQPIKVATQPELqvPGPVENLHAVSTSPTSILITWEPPayAN 555
Cdd:COG3401   279 VATVT--TTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTP--PAAPSGLTATAVGSSSITLSWTAS--SD 352

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  556 GPVQGYRLFCTEVSTGKEQNI--EVDGLSYKLEGLKKFTEYTLRFLAYNRYGP-GVSTDDITVVTLSDVPSAPPQNISLE 632
Cdd:COG3401   353 ADVTGYNVYRSTSGGGTYTKIaeTVTTTSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVSATTASAASGESLTASVDA 432

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  633 VVNSRSIKVSWLP----PPSGTQNGFITGYKIRHRKTTRRGEME-TLEPNNLWYLFTGLEKGSQYSFQVSAMTVNGTGPP 707
Cdd:COG3401   433 VPLTDVAGATAAAsaasNPGVSAAVLADGGDTGNAVPFTTTSSTvTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVI 512

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  708 SNWYTAETPeNDLDESQVPDQPSSLHVRPQTNCIIMSWTPPLNPNIVVRGYIIGYGVGSPYAETVRVDSKQRYYSIERLE 787
Cdd:COG3401   513 GASAAAAVG-GAPDGTPNVTGASPVTVGASTGDVLITDLVSLTTSASSSVSGAGLGSGNLYLITTLGGSLLTTTSTNTND 591

                         410
                  ....*....|..
gi 117168295  788 SSSHYVISLKAF 799
Cdd:COG3401   592 VAGVHGGTLLVL 603

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 79.46 E-value: 1.16e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  429 PSAPRDVLPVLVSSRFVRLSWRPPAEAKGNIQTFTVFFSREGDNRERALNTTQPGSLQLTVGNLKPEAMYTFRVVAYNEW 508
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 117168295  509 GPGESSQPIKVAT 521
Cdd:cd00063    81 GESPPSESVTVTT 93

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 76.77 E-value: 8.68e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  625 PPQNISLEVVNSRSIKVSWLPPPSGtqNGFITGYKIRHRKTTRRG--EMETLEPNNLWYLFTGLEKGSQYSFQVSAMTVN 702
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDwkEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 117168295  703 GTGPPSNWYTAET 715
Cdd:cd00063    81 GESPPSESVTVTT 93

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 74.85 E-value: 4.12e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    337 PSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDV-VIPSDYFQIVGGSN---LRILGVVKSDEGFYQCVAENEAGNAQSS 412
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 117168295    413 AQLIV 417
Cdd:smart00410   81 TTLTV 85

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 74.74 E-value: 4.15e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHP-SNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNA 409
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDI 80


                  ....*...
gi 117168295  410 QSSAQLIV 417
Cdd:cd20978    81 YTETLLHV 88

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 74.17 E-value: 6.47e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  333 FLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSnLRILGVVKSDEGFYQCVAENEAGNAQSS 412
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD-LRITKLSLSDSGMYQCVAENKHGTIYAS 80


                  ....*
gi 117168295  413 AQLIV 417
Cdd:cd05728    81 AELAV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 73.37 E-value: 1.08e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295   139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 73.70 E-value: 1.13e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  244 QRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLG-GSNLLISNVTDDDSGTYTCVVTYKNENiSAS 322
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVREnGTTLTIRNIRRSDMGIYLCIASNGVPG-SVE 85


                  ....*..
gi 117168295  323 AELTVLV 329
Cdd:cd20970    86 KRITLQV 92

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 73.03 E-value: 1.56e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    625 PPQNISLEVVNSRSIKVSWLPPPSGTQNGFITGYKIRHRKTTRRGEMETLEPNNLWYLFTGLEKGSQYSFQVSAMTVNGT 704
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGE 82


                    .
gi 117168295    705 G 705
Cdd:smart00060   83 G 83

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 72.82 E-value: 1.68e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  244 QRPSNVIAIEGKDAVLECCVS-GYPPPSFTWLRGEEVIQLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVT-YKNENISA 321
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATnMVGERESR 81


                  ....*.
gi 117168295  322 SAELTV 327
Cdd:cd05724    82 AARLSV 87

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 2.44e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  592 TEYTLRFLAYNRYGPGVSTDDITVVTLSDVPSAPPQNISLEVVNSRSIKVSWLPPPSGTQNGFITGYKIRHRKTTRRGEm 671
Cdd:COG3401     1 TGSSYLTSLDAGIAASAAANTAVNALSKAGGSGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGV- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  672 eTLEPNNLWYLFTGLEKGSQYSFQVSAMTVNGTGPPSNWYTAETPEN-DLDESQVPDQPSSLHVRPQTNCIIMSWTPPLN 750
Cdd:COG3401    80 -AAVAVAAAPPTATGLTTLTGSGSVGGATNTGLTSSDEVPSPAVGTAtTATAVAGGAATAGTYALGAGLYGVDGANASGT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  751 PNIVVRGYIIGYGVGSPYAETV-----RVDSKQRYYSIERLESSSHYVISLKAFNNAGEGVPlyesATTRSITDPTdpvd 825
Cdd:COG3401   159 TASSVAGAGVVVSPDTSATAAVattslTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAP----SNEVSVTTPT---- 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  826 yypllddfptsgpdvsTPMLPPVGVQAVALTHEAVRVSWADNSVPknqktsDVRLYTVRWRTSfsASAKYKS-EDTTSLS 904
Cdd:COG3401   231 ----------------TPPSAPTGLTATADTPGSVTLSWDPVTES------DATGYRVYRSNS--GDGPFTKvATVTTTS 286

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  905 YTATGLKPNTMYEFSVM-VTKNRRSSTWSMTAHATTYEAAPTsAPKDLTViTREGkPRAVIVSWQPPleANGKITAYILF 983
Cdd:COG3401   287 YTDTGLTNGTTYYYRVTaVDAAGNESAPSNVVSVTTDLTPPA-APSGLTA-TAVG-SSSITLSWTAS--SDADVTGYNVY 361

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  984 YTLDKNIPIDdWIMETISGdrLTHQIMDLSLDTMYYFRIQARNVKGV-GPLSDPI 1037
Cdd:COG3401   362 RSTSGGGTYT-KIAETVTT--TSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEV 413

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 71.83 E-value: 3.53e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVI--QLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVT 313
Cdd:pfam13927    8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 71.21 E-value: 4.56e-15

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  157 VLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.13 E-value: 9.15e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPlpgDSRVVVLPSGA---LQISRLQPGDSGVYRCSARNP 217
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS---SDRFKVTYEGGtytLTISNVQPDDSGKYTCVATNS 78


                   .
gi 117168295   218 A 218
Cdd:pfam07679   79 A 79

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 70.99 E-value: 1.01e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSD----YFQIVGGSNLRILGVVKSDEGFYQCVAENEA 406
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSahkmLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 117168295  407 GNAQSSAQLIV 417
Cdd:cd05744    81 GENSFNAELVV 91

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 70.61 E-value: 1.21e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    147 ESITAFMGDTVLLKCEVIGEPMPTIHWQKnqQDLNPLPGDSRVVVLPSG---ALQISRLQPGDSGVYRCSARNPASIRTG 223
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYK--QGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASS 79


                    .
gi 117168295    224 N 224
Cdd:smart00410   80 G 80

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 69.28 E-value: 2.44e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  348 IEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIV---GGSNLRILGVVKSDEGFYQCVAENEAGNAQSS 412
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 69.76 E-value: 2.67e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVV----IPSDY-FQIVGG-SNLRILGVVKSDEGFYQCVAEN 404
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpssIPGKYkIESEYGvHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 117168295  405 EAGNAQSSAQLIV 417
Cdd:cd20951    81 IHGEASSSASVVV 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 69.37 E-value: 3.49e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   529 GPVENLHAVSTSPTSILITWEPPAYANGPVQGYRLFCTEVSTGK-EQNIEVDG--LSYKLEGLKKFTEYTLRFLAYNRYG 605
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEpWNEITVPGttTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ..
gi 117168295   606 PG 607
Cdd:pfam00041   81 EG 82

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 68.80 E-value: 4.07e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    528 PGPVENLHAVSTSPTSILITWEPPAYAN--GPVQGYRL-FCTEVSTGKEQNIEVDGLSYKLEGLKKFTEYTLRFLAYNRY 604
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVeYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 117168295    605 GPG 607
Cdd:smart00060   81 GEG 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 68.75 E-value: 4.86e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295   330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIP---SDYFQIVGGSNLRILGVVKSDEGFYQCVAEN 404
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 68.33 E-value: 6.99e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  347 DIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQL 415
Cdd:cd20957    18 TAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 68.29 E-value: 8.32e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  946 SAPKDLTVitREGKPRAVIVSWQPPLEANGKITAYILFYTLDKNipiDDWI-METISGDRLTHQIMDLSLDTMYYFRIQA 1024
Cdd:cd00063     2 SPPTNLRV--TDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGS---GDWKeVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

                          90
                  ....*....|....*..
gi 117168295 1025 RNVKGVGPLSDPILFRT 1041
Cdd:cd00063    77 VNGGGESPPSESVTVTT 93

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 67.74 E-value: 8.77e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  257 AVLECCVSGYPPPSFTWLRGEEVIQL--RSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 67.91 E-value: 9.70e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  142 FLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKnqqDLNPLPG-DSRVVVLPSGALQISRLQPGDSGVYRCSARNP 217
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLK---DGVPLLGkDERITTLENGSLQIKGAEKSDTGEYTCVALNL 75

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 68.05 E-value: 1.01e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNG-DVVIPSDYFQI-VGGSNLRILGVVKSDEGFYQCVAENEAG 407
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqPLQYAADRSTCeAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                          90
                  ....*....|
gi 117168295  408 NAQSSAQLIV 417
Cdd:cd20976    81 QVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 67.91 E-value: 1.27e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLL---GGSNLLISNVTDDDSGTYTCVVTYKNEN 318
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVrenGRHSLIIEPVTKRDAGIYTCIARNRAGE 82


                  ....*....
gi 117168295  319 ISASAELTV 327
Cdd:cd05744    83 NSFNAELVV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 67.49 E-value: 1.47e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  345 SMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd04969    17 GGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 67.96 E-value: 1.62e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   43 VSEPSDAVTMRGGNVLLNCSAESdRGVPVIKWKKDGLILALGMDDRKQQ---LPNGSLLIQNILHSRHHKPDEGLYQCEA 119
Cdd:cd07693     4 VEHPSDLIVSKGDPATLNCKAEG-RPTPTIQWLKNGQPLETDKDDPRSHrivLPSGSLFFLRVVHGRKGRSDEGVYVCVA 82

                          90
                  ....*....|....*...
gi 117168295  120 SlADSGSIISRTAKVTVA 137
Cdd:cd07693    83 H-NSLGEAVSRNASLEVA 99

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 67.04 E-value: 1.62e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  334 LNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNgDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSA 413
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKE-DGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASA 79


                  ....
gi 117168295  414 QLIV 417
Cdd:cd05725    80 TLTV 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 67.05 E-value: 1.83e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   946 SAPKDLTVITREgkPRAVIVSWQPPLEANGKITAYILFY-TLDKNipiDDWIMETISGDRLTHQIMDLSLDTMYYFRIQA 1024
Cdd:pfam00041    1 SAPSNLTVTDVT--STSLTVSWTPPPDGNGPITGYEVEYrPKNSG---EPWNEITVPGTTTSVTLTGLKPGTEYEVRVQA 75

                           90
                   ....*....|
gi 117168295  1025 RNVKGVGPLS 1034
Cdd:pfam00041   76 VNGGGEGPPS 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 65.51 E-value: 6.43e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   625 PPQNISLEVVNSRSIKVSWLPPPSGtqNGFITGYKIRHRKTTR-RGEMETLEPNNLW-YLFTGLEKGSQYSFQVSAMTVN 702
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDG--NGPITGYEVEYRPKNSgEPWNEITVPGTTTsVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 117168295   703 GTGPPS 708
Cdd:pfam00041   80 GEGPPS 85

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 65.35 E-value: 8.75e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSNLL-ISNVTDDDSGTYTCVVTYKNENISASAE 324
Cdd:cd20976     8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELhIQDVLPEDHGTYTCLAKNAAGQVSCSAW 87


                  ...
gi 117168295  325 LTV 327
Cdd:cd20976    88 VTV 90

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 64.81 E-value: 1.75e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNpLPGDSRVVVLPSGALQI-----SRLQPGDSGVYRCS 213
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLN-LVSDERRQQLPNGSLLItsvvhSKHNKPDEGFYQCV 79


                  ...
gi 117168295  214 ARN 216
Cdd:cd05722    80 AQN 82

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 63.53 E-value: 4.21e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  329 VPPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVG---GSNLRILGVVKSDEGFYQCVAENE 405
Cdd:cd05747     2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSteyKSTFEISKVQMSDEGNYTVVVENS 81

                          90
                  ....*....|
gi 117168295  406 AGNAQSSAQL 415
Cdd:cd05747    82 EGKQEAQFTL 91

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 63.18 E-value: 4.87e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  150 TAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLnPlpgDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05725     8 VVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-P---KGRYEILDDHSLKIRKVTAGDMGSYTCVAEN 70

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 62.80 E-value: 5.98e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  243 LQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRskKYSLLGGSNLLISNVTDDDSGTYTCVVtyknEN---- 318
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG--RYEILDDHSLKIRKVTAGDMGSYTCVA----ENmvgk 74


                  ....*....
gi 117168295  319 ISASAELTV 327
Cdd:cd05725    75 IEASATLTV 83

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 62.97 E-value: 6.11e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  149 ITAFMGDTVLLKCEVIGEPMPTIHWQKnqqDLNPLPGDSRVVVLPSGALQISRLQPG-DSGVYRCSARNP 217
Cdd:cd20958    10 LTAVAGQTLRLHCPVAGYPISSITWEK---DGRRLPLNHRQRVFPNGTLVIENVQRSsDEGEYTCTARNQ 76

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 62.13 E-value: 1.02e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295   42 FVSEPSDAVTMRGGNVLLNCSAESDRgVPVIKWKKDGLILaLGMDDRKQQLPNGSLLIQNIlhsrhHKPDEGLYQCEAS 120
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEP-VPTISWLKDGVPL-LGKDERITTLENGSLQIKGA-----EKSDTGEYTCVAL 73

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 61.64 E-value: 1.61e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  241 YFLQRP-SNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSnLLISNVTDDDSGTYTCVVTYKNENI 319
Cdd:cd20978     2 KFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIGDI 80


                  ....*...
gi 117168295  320 SASAELTV 327
Cdd:cd20978    81 YTETLLHV 88

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 61.73 E-value: 2.29e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  240 LYFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRS--KKYSLLGGSnLLISNVT-----DDDSGTYTCVV 312
Cdd:cd05722     2 LYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSdeRRQQLPNGS-LLITSVVhskhnKPDEGFYQCVA 80

                          90
                  ....*....|....*..
gi 117168295  313 TYKNEN--ISASAELTV 327
Cdd:cd05722    81 QNESLGsiVSRTARVTV 97

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 61.09 E-value: 2.67e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    429 PSAPRDVLPVLVSSRFVRLSWRPPAEAKGN--IQTFTVFFSREGDNRERAlnTTQPGSLQLTVGNLKPEAMYTFRVVAYN 506
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEV--NVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 117168295    507 EWGPG 511
Cdd:smart00060   79 GAGEG 83

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 60.93 E-value: 2.83e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPsGALQISRLQPGDSGVYRCSARNP 217
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDG-RTLIFSNLQPNDTAVYQCNASNV 76

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 60.72 E-value: 3.35e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSkKYSLLGGSNLLISNVTDDDSGTYTCV 311
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENN-RIAVLESGSLRIHNVQKEDAGQYRCV 70

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 59.57 E-value: 6.47e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQqdlNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNP-ASIRT 222
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGG---SQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIvGSQRT 68

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 59.85 E-value: 7.97e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQdlnPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd20957     1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK---PLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDG 77

                          90
                  ....*....|..
gi 117168295  219 SIRTGNeAEVRI 230
Cdd:cd20957    78 DSAQAT-AELKL 88

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 59.17 E-value: 1.20e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    946 SAPKDLTVITREgkPRAVIVSWQPPLEANGkiTAYILFYTLDKNIPIDDWIMETISGDRLTHQIMDLSLDTMYYFRIQAR 1025
Cdd:smart00060    2 SPPSNLRVTDVT--STSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 117168295   1026 NVKGVG 1031
Cdd:smart00060   78 NGAGEG 83

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 59.03 E-value: 1.46e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQDLnpLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPASIRTG 223
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWISPEGKL--ISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATA 82

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 59.01 E-value: 1.53e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLL----GGSNLLISNVTDDDSGTYTcvVTYKNE 317
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYqdncGRICLLIQNANKKDAGWYT--VSAVNE 80

                          90
                  ....*....|..
gi 117168295  318 N--ISASAELTV 327
Cdd:cd05892    81 AgvVSCNARLDV 92

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 58.77 E-value: 1.72e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGgsNLLISNVTDDDSGTYTCVVTYKNENISA 321
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAG--DLRITKLSLSDSGMYQCVAENKHGTIYA 79


                  ....*.
gi 117168295  322 SAELTV 327
Cdd:cd05728    80 SAELAV 85

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 58.74 E-value: 1.79e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  350 FECAVSGKPVPTVNWMKNGDVVIPSDYFQIV----GGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20973    17 FDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqdedGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 57.24 E-value: 4.85e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    726 PDQPSSLHVRPQT-NCIIMSWTPPLNPNIV--VRGYIIGYGVGSPYAETVRVDSKQRYYSIERLESSSHYVISLKAFNNA 802
Cdd:smart00060    1 PSPPSNLRVTDVTsTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 117168295    803 GEG 805
Cdd:smart00060   81 GEG 83

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 57.41 E-value: 4.87e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  356 GKPVPTVNWMKNGDVVIPSD-YFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSS-AQLIV 417
Cdd:cd05724    24 GHPEPTVSWRKDGQPLNLDNeRVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRaARLSV 87

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 57.51 E-value: 6.58e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  846 PPVGVQAVALTHEAVRVSWadnSVPKNqKTSDVRLYTVRWR-TSFSASAKYKSEDTTSLSYTATGLKPNTMYEFSVMVTK 924
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSW---TPPED-DGGPITGYVVEYReKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|....*
gi 117168295  925 NRRSSTWSMTAHATT 939
Cdd:cd00063    79 GGGESPPSESVTVTT 93

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.12 E-value: 7.28e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISA 321
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81


                  ....*.
gi 117168295  322 SAELTV 327
Cdd:cd20952    82 SAVLDV 87

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 57.07 E-value: 7.57e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  241 YFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLG-GSNLLISNVTDDDSGTYTCVVTYKNENI 319
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVdGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                  ....*....
gi 117168295  320 SASAELTVL 328
Cdd:cd04978    81 LANAFLHVL 89

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 56.64 E-value: 8.25e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  151 AFMGDTVLLKCEV-IGEPMPTIHWQKNQQDLNPLpgDSRVVVLPSGALQISRLQPGDSGVYRCSARNPASIRTGNEAEVR 229
Cdd:cd05724     9 VAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLD--NERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAARLS 86


                  .
gi 117168295  230 I 230
Cdd:cd05724    87 V 87

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 56.75 E-value: 8.85e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  337 PSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSN--LRILGVVKSDEGFYQCVAENEA-GNAQSSA 413
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGttLTIRNIRRSDMGIYLCIASNGVpGSVEKRI 88


                  ....
gi 117168295  414 QLIV 417
Cdd:cd20970    89 TLQV 92

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 56.72 E-value: 1.08e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNG---DVVIPSDYFQIVGGSnLRILGVV-----KSDEGFYQCV 401
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGvllNLVSDERRQQLPNGS-LLITSVVhskhnKPDEGFYQCV 79


                  ....
gi 117168295  402 AENE 405
Cdd:cd05722    80 AQNE 83

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 56.79 E-value: 1.35e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGD-------------VVIPSD---YFQIVGGSNlrilgvVKSD 394
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQpletdkddprshrIVLPSGslfFLRVVHGRK------GRSD 74

                          90
                  ....*....|....*..
gi 117168295  395 EGFYQCVAENEAGNAQS 411
Cdd:cd07693    75 EGVYVCVAHNSLGEAVS 91

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 55.66 E-value: 1.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   246 PSNVIAIEGKDAVLECCVS-GYPPPSFTWLRGEEVIQLRSKK---YSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISA 321
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVkhdNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82


                   ....
gi 117168295   322 SAEL 325
Cdd:pfam00047   83 STSL 86

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 55.89 E-value: 2.43e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  142 FLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSG---ALQISRLQPGDSGVYRCSARN 216
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKN 80

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 55.50 E-value: 2.47e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   430 SAPRDVLPVLVSSRFVRLSWRPPAEAKGNIQTFTVFFSREGDNrERALNTTQPGSL-QLTVGNLKPEAMYTFRVVAYNEW 508
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSG-EPWNEITVPGTTtSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 117168295   509 GPGESS 514
Cdd:pfam00041   80 GEGPPS 85

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 55.48 E-value: 2.61e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   45 EPSDAVTMRGGNVLLNCSAESDRGVPVIKWKKDGLILALgMDDRKQQLPNGSLLIQNIlhsrhHKPDEGLYQCEASLAdS 124
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNL-DNERVRIVDDGNLLIAEA-----RKSDEGTYKCVATNM-V 75

                          90
                  ....*....|..
gi 117168295  125 GSIISRTAKVTV 136
Cdd:cd05724    76 GERESRAARLSV 87

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 55.11 E-value: 2.75e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  247 SNVIAIEGKDAVLECCVSGYPPPSFTWLR-GEEVIQLRSKKYSLlgGSNLLISNVTDDDSGTYTCvvTYKNENISASAEL 325
Cdd:cd05731     3 SSTMVLRGGVLLLECIAEGLPTPDIRWIKlGGELPKGRTKFENF--NKTLKIENVSEADSGEYQC--TASNTMGSARHTI 78


                  ....
gi 117168295  326 TVLV 329
Cdd:cd05731    79 SVTV 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 55.41 E-value: 2.89e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  145 QTESITAFMGDTVLLKCEVIGEPMPTIHWQKNqqdLNPLPGDSRVVVlpSGA-LQISRLQPGDSGVYRCSARN 216
Cdd:cd05851     7 KFKDTYALKGQNVTLECFALGNPVPVIRWRKI---LEPMPATAEISM--SGAvLKIFNIQPEDEGTYECEAEN 74

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 54.94 E-value: 3.59e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  336 HPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQS 411
Cdd:cd20968     5 PPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 54.56 E-value: 3.59e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  344 ESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 55.35 E-value: 3.74e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  254 GKDAVLECCVSGYPPPSFTWLR-GEEVIQLRSKKYSLLG-GSNLLISNVTDDDSGTYTCVVtyKNE 317
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKnGMDINPKLSKQLTLIAnGSELHISNVRYEDTGAYTCIA--KNE 78

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 54.72 E-value: 3.91e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  338 SNLYAYESMDIEFECAVSGKPVPTVNWMK-NGDvvIPSDYFQIVG-GSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQL 415
Cdd:cd05731     3 SSTMVLRGGVLLLECIAEGLPTPDIRWIKlGGE--LPKGRTKFENfNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                  ..
gi 117168295  416 IV 417
Cdd:cd05731    81 TV 82

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 54.91 E-value: 3.98e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  153 MGDTVLLKCEVIGEPMPTIHWQKNQQdlnPLPGDSRVVVLpSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05728    13 IGSSLRWECKASGNPRPAYRWLKNGQ---PLASENRIEVE-AGDLRITKLSLSDSGMYQCVAEN 72

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.90 E-value: 4.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKS---DEGFYQCVAENEA 406
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAfeeDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 117168295  407 GNAQSSAQLIV 417
Cdd:cd20972    81 GSDTTSAEIFV 91

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 54.86 E-value: 4.94e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  337 PSNLYAYESMDIEFECAVSGKPVPTVNWMKNgDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLI 416
Cdd:cd04968     8 PADTYALKGQTVTLECFALGNPVPQIKWRKV-DGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRII 86


                  .
gi 117168295  417 V 417
Cdd:cd04968    87 V 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 54.32 E-value: 5.29e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   245 RPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQlrskkysllGGSNLLISNVTDDDSGTYTCVVTYKNENI-SASA 323
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS---------SSPNFFTLSVSAEDSGTYTCVARNGRGGKvSNPV 75


                   ....
gi 117168295   324 ELTV 327
Cdd:pfam13895   76 ELTV 79

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 54.96 E-value: 5.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKN-QQDL----NPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSAR 215
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEgSQNLlfpyQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQAL 80

                          90
                  ....*....|....
gi 117168295  216 NPA-SIRTGNEAEV 228
Cdd:cd05726    81 NVAgSILAKAQLEV 94

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 54.42 E-value: 6.20e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  726 PDQPSSLHVRPQT-NCIIMSWTPPLNPNIVVRGYIIGY-GVGSPYAETVRV-DSKQRYYSIERLESSSHYVISLKAFNNA 802
Cdd:cd00063     1 PSPPTNLRVTDVTsTSVTLSWTPPEDDGGPITGYVVEYrEKGSGDWKEVEVtPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|..
gi 117168295  803 GEGVPLYESATT 814
Cdd:cd00063    81 GESPPSESVTVT 92

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 54.48 E-value: 6.30e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  150 TAFMGDTVLLKCEVIGEPMPTIHWQKNQQD-----LNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05765    11 TVKVGETASFHCDVTGRPQPEITWEKQVPGkenliMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSG 84

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 54.87 E-value: 6.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDL--NPLPGDSRVVVLPSGALQISRLQPG-----DSGVYRCS 213
Cdd:cd07693     2 RIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetDKDDPRSHRIVLPSGSLFFLRVVHGrkgrsDEGVYVCV 81


                  ...
gi 117168295  214 ARN 216
Cdd:cd07693    82 AHN 84

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 54.47 E-value: 7.38e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  348 IEFECAVSGKPVPTVNWMKNGDVVIPSDYfqiVGGSNLR-------ILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05857    22 VKFRCPAAGNPTPTMRWLKNGKEFKQEHR---IGGYKVRnqhwsliMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 53.34 E-value: 7.53e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  348 IEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQL 415
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 54.11 E-value: 7.79e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  245 RP-SNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQL--RSKKYSllGGSnLLISNVT-DDDSGTYTCVVTYKnENIS 320
Cdd:cd20958     5 RPmGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLnhRQRVFP--NGT-LVIENVQrSSDEGEYTCTARNQ-QGQS 80


                  ....*....
gi 117168295  321 ASAELTVLV 329
Cdd:cd20958    81 ASRSVFVKV 89

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 54.04 E-value: 8.19e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  352 CAVSGKPVPTVNWMKNGDVVIPSD--YFQIVGGSnLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20952    21 CQATGEPVPTISWLKDGVPLLGKDerITTLENGS-LQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 54.04 E-value: 9.53e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTW--LRGEEVIQ-----LRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTY 314
Cdd:cd05734     4 FVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkhSKGSGVPQfqhivPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSN 83

                          90
                  ....*....|....
gi 117168295  315 K-NENISASAELTV 327
Cdd:cd05734    84 DvGADISKSMYLTV 97

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 53.62 E-value: 1.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  240 LYFLQRPSnvIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQlRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENI 319
Cdd:cd04969     5 LNPVKKKI--LAAKGGDVIIECKPKASPKPTISWSKGTELLT-NSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81


                  ....*...
gi 117168295  320 SASAELTV 327
Cdd:cd04969    82 NSTGSLSV 89

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 53.57 E-value: 1.29e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIV----GGSNLRILGVVKSDEGFYQCVAENEA 406
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLvrenGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 117168295  407 GNAQSSAQLIV 417
Cdd:cd20990    81 GQNSFNLELVV 91

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 53.55 E-value: 1.40e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  149 ITAFMGDTVLLKCEVIGEPMPTIHWQKNQqdlNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWLHNG---KPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATN 75

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 53.32 E-value: 1.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  145 QTESITAFMGDTVLLKCEVIGEPMPTIHWQKnqqdLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNpasIRTGN 224
Cdd:cd04968     7 FPADTYALKGQTVTLECFALGNPVPQIKWRK----VDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAEN---SRGKD 79


                  ....*.
gi 117168295  225 EAEVRI 230
Cdd:cd04968    80 TVQGRI 85

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 53.39 E-value: 1.46e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  149 ITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGA-LQISRLQPGDSGVYRCSARNPASIRTGN 224
Cdd:cd05763     9 ITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDvFFIVDVKIEDTGVYSCTAQNSAGSISAN 85

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 53.28 E-value: 1.49e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  243 LQRPSNVIAIEGKDAVLEC-CVSGYPPPSFTWLR-GEEVIQLRSKKYSLLGG---SNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCeATSENPSPRYRWFKdGKELNRKRPKNIKIRNKkknSELQINKAKLEDSGEYTCVVENILG 82

                          90
                  ....*....|
gi 117168295  318 NISASAELTV 327
Cdd:cd05750    83 KDTVTGNVTV 92

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 53.10 E-value: 1.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTW-LRGEEVIQLRS--KKYSLLgGSNLLISNVTDDDSGTYTCVVTYKNEN 318
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWhFNGQPISASVAdmSKYRIL-ADGLLINKVTQDDTGEYTCRAYQVNSI 80


                  ....*....
gi 117168295  319 ISASAELTV 327
Cdd:cd20949    81 ASDMQERTV 89

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 53.18 E-value: 1.79e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  241 YFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLL---GGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd20990     2 HFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVrenGVHSLIIEPVTSRDAGIYTCIATNRAG 81

                          90
                  ....*....|
gi 117168295  318 NISASAELTV 327
Cdd:cd20990    82 QNSFNLELVV 91

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 52.89 E-value: 1.88e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295     46 PSDAVTMRGGNVLLNCSAESDrGVPVIKWKKDGLILaLGMDDRKQQLPNG---SLLIQNILHSrhhkpDEGLYQCEASla 122
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGS-PPPEVTWYKQGGKL-LAESGRFSVSRSGstsTLTISNVTPE-----DSGTYTCAAT-- 71

                            90
                    ....*....|....
gi 117168295    123 DSGSIISRTAKVTV 136
Cdd:smart00410   72 NSSGSASSGTTLTV 85

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 53.02 E-value: 2.28e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  242 FLQRPSNVIAIEGKD---AVLECCVSGYPPPSFTWLR-GEEVIQLRSKKYSLLGGsNLLISN-VTDDDSGTYTCVVT 313
Cdd:cd04967     4 FEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMnGTEIDLESDYRYSLVDG-TLVISNpSKAKDAGHYQCLAT 79

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 52.59 E-value: 2.75e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVlPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHV-SSGALILTDVQPSDTAVYQCEARN 75

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 52.49 E-value: 3.62e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQK-----NQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCS 213
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHskgsgVPQFQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCK 80


                  ...
gi 117168295  214 ARN 216
Cdd:cd05734    81 VSN 83

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 52.20 E-value: 3.67e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQlRSKKYSLLGGSN---LLISNVTDDDSGTYTCVVTYKNEN 318
Cdd:cd20972     4 FIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQ-NSPDIQIHQEGDlhsLIIAEAFEEDTGRYSCLATNSVGS 82


                  ....*....
gi 117168295  319 ISASAELTV 327
Cdd:cd20972    83 DTTSAEIFV 91

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 52.42 E-value: 3.70e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSK--KYSLL---GGSNLLISNVTDDDSGTYTCVVTYKN 316
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgKYKIEseyGVHVLHIRRVTVEDSAVYSAVAKNIH 82

                          90
                  ....*....|.
gi 117168295  317 ENISASAELTV 327
Cdd:cd20951    83 GEASSSASVVV 93

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 52.24 E-value: 3.85e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  148 SITAFMGDTVLLKCEVIGEPMPTIHWQKNQqdlNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd20968     8 NVTIIEGLKAVLPCTTMGNPKPSVSWIKGD---DLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKN 73

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 52.33 E-value: 3.94e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  269 PSFTWLRGEEVIQLRsKKYSLLGgSNLLISNVTDDDSGTYTCVVTY----KNENISASAELTVLV 329
Cdd:cd05757    30 PPIQWYKDCKPLQGD-KRFIPKG-SKLLIQNVTEEDAGNYTCKFTYthngKQYNVTRTISLTVTE 92

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 52.46 E-value: 4.57e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   246 PSNVIAIEGKDAVLECCVSGY---PPPSFTWLRG------EEVIQLRSKK---------YSLLGGSN-----LLISNVTD 302
Cdd:pfam07686    3 PREVTVALGGSVTLPCTYSSSmseASTSVYWYRQppgkgpTFLIAYYSNGseegvkkgrFSGRGDPSngdgsLTIQNLTL 82

                           90       100
                   ....*....|....*....|....*..
gi 117168295   303 DDSGTYTCVVTYKNENI-SASAELTVL 328
Cdd:pfam07686   83 SDSGTYTCAVIPSGEGVfGKGTRLTVL 109

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 51.86 E-value: 5.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  244 QRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSL-LGGSNLLISNVTDDDSGTYTCVVTYKNENISAS 322
Cdd:cd05730     8 QSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFnEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAE 87


                  ....*..
gi 117168295  323 AELTVLV 329
Cdd:cd05730    88 IHLKVFA 94

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 51.86 E-value: 5.26e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  352 CAVSGKPVPTVNWMKNGDVVIPSD--YFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05730    25 CDADGFPEPTMTWTKDGEPIESGEekYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.41 E-value: 5.92e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    42 FVSEPSDAVTMRGGNVLLNCSAESDrGVPVIKWKKDG-LILALGMDDRKQQLPNGSLLIQNILHSrhhkpDEGLYQCEAS 120
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGS-PPPTITWYKNGePISSGSTRSRSLSGSNSTLTISNVTRS-----DAGTYTCVAS 77

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 51.87 E-value: 6.45e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  242 FLQRPSNVI---AIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSK-KYSLLGGsNLLISNVTD-DDSGTYTCVVT 313
Cdd:cd05848     4 FVQEPDDAIfptDSDEKKVILNCEARGNPVPTYRWLRNGTEIDTESDyRYSLIDG-NLIISNPSEvKDSGRYQCLAT 79

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 50.79 E-value: 6.50e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295   57 VLLNCSAESDRgVPVIKWKKDGLILALG-MDDRKQQLPNGSLLIQNILHSrhhkpDEGLYQCEASLADSGSIISRT 131
Cdd:cd00096     1 VTLTCSASGNP-PPTITWYKNGKPLPPSsRDSRRSELGNGTLTISNVTLE-----DSGTYTCVASNSAGGSASASV 70

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 51.30 E-value: 6.87e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  337 PSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVV--IPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQ 414
Cdd:cd04978     6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIepAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAF 85


                  ...
gi 117168295  415 LIV 417
Cdd:cd04978    86 LHV 88

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 51.20 E-value: 1.02e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDY--FQI---VGGSNLRILGVVKSDEGFYQCVAENE 405
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpgVQIsfsDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 117168295  406 AGNAQSSAQLIV 417
Cdd:cd20974    81 SGQATSTAELLV 92

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 50.99 E-value: 1.03e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  254 GKDAVLECCVSGYPPPSFTWLRGEEVIQlRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAEL 325
Cdd:cd20957    16 GRTAVFNCSVTGNPIHTVLWMKDGKPLG-HSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 50.92 E-value: 1.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIP-----SDYFQIVGGSNLRILGVVKSDEGFYQCVAENE 405
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYntdriSLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|..
gi 117168295  406 AGNAQSSAQLIV 417
Cdd:cd05892    81 AGVVSCNARLDV 92

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 50.77 E-value: 1.32e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  351 ECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05852    23 ECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 50.49 E-value: 1.49e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   727 DQPSSLHVRPQT-NCIIMSWTPPLNPNIVVRGYIIGYGV--GSPYAETVRVDSKQRYYSIERLESSSHYVISLKAFNNAG 803
Cdd:pfam00041    1 SAPSNLTVTDVTsTSLTVSWTPPPDGNGPITGYEVEYRPknSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....
gi 117168295   804 EGVP 807
Cdd:pfam00041   81 EGPP 84

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 50.72 E-value: 1.55e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  352 CAVSGKPVPTVNWMKNGDVVIP--SDYFQIVG-GSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05736    22 CHAEGIPLPRVQWLKNGMDINPklSKQLTLIAnGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 50.31 E-value: 1.69e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLR--GEEVIQLRSKKYSLLGGSNLL-ISNVTDDDSGTYTCVVTYKNEN 318
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKdgGTDFPAARERRMHVMPEDDVFfIVDVKIEDTGVYSCTAQNSAGS 81

                          90
                  ....*....|
gi 117168295  319 ISASAELTVL 328
Cdd:cd05763    82 ISANATLTVL 91

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 50.29 E-value: 1.72e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  338 SNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQ 410
Cdd:cd05876     3 SSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 50.57 E-value: 1.83e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   41 HFVSEPSDAVTMRGGNVLLNCSAESdRGVPVIKWK--------KDGLILALGmdDRKQQLPNGSLLIQNILHSrhhkpDE 112
Cdd:cd05734     3 RFVVQPNDQDGIYGKAVVLNCSADG-YPPPTIVWKhskgsgvpQFQHIVPLN--GRIQLLSNGSLLIKHVLEE-----DS 74

                          90       100
                  ....*....|....*....|....
gi 117168295  113 GLYQCEASlADSGSIISRTAKVTV 136
Cdd:cd05734    75 GYYLCKVS-NDVGADISKSMYLTV 97

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 50.34 E-value: 1.85e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPASI 220
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGV 81

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 50.40 E-value: 1.88e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  156 TVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNPASIRTGNEAEVRI 230
Cdd:cd05738    16 TATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSAPANLYV 90

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 49.51 E-value: 2.46e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  347 DIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSN---LRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05748     9 SLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASstsLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 50.16 E-value: 2.50e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  344 ESMDIEFECAVSGKPVPTVNWMKNGDVVIPsDYFQIV-----GGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20975    14 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRP-DQRRFAeeaegGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 91

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 50.05 E-value: 2.55e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  243 LQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVI------QLRSKKYSllggSNLLISNVTDDDSGTYTCVVtyKN 316
Cdd:cd05747     7 LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIvssqrhQITSTEYK----STFEISKVQMSDEGNYTVVV--EN 80

                          90
                  ....*....|.
gi 117168295  317 ENISASAELTV 327
Cdd:cd05747    81 SEGKQEAQFTL 91

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.22 E-value: 2.62e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  143 LSQTESITAFMGDTVLLKCEVIGEPMPTIHWQK-------NQQDLnplpgDSRVVV---LPSGALQISRLQPGDSGVYRC 212
Cdd:cd05732     5 ITYLENQTAVELEQITLTCEAEGDPIPEITWRRatrgisfEEGDL-----DGRIVVrghARVSSLTLKDVQLTDAGRYDC 79


                  ....*
gi 117168295  213 SARNP 217
Cdd:cd05732    80 EASNR 84

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 49.99 E-value: 2.85e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  253 EGKDAVLEC-CVSGYPPPSFTWLRGE---------EVIQLRSKKysllGGSNLLISNVTDDDSGTYTCVVTYKNENISAS 322
Cdd:cd05895    13 AGSKLVLRCeTSSEYPSLRFKWFKNGkeinrknkpENIKIQKKK----KKSELRINKASLADSGEYMCKVSSKLGNDSAS 88


                  ....*
gi 117168295  323 AELTV 327
Cdd:cd05895    89 ANVTI 93

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 49.63 E-value: 3.26e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  339 NLYAYESMDIEFECAVSGKPVPTVNWMKNGDVvIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05851    10 DTYALKGQNVTLECFALGNPVPVIRWRKILEP-MPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYV 87

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 49.47 E-value: 3.33e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  153 MGDTVLLKCEVIGEPMPTIHWQKNQQDL-NPLPGDSRvvvLPSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLtPPEIGENK---KKKWTLSLKNLKPEDSGKYTCHVSNRA 81

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 49.64 E-value: 3.54e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNP-LPGDSRVVVLPSGaLQISRLQPGDSGVYRCSARNPAS 219
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISAsVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQVNS 79


                  ...
gi 117168295  220 IRT 222
Cdd:cd20949    80 IAS 82

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 49.50 E-value: 3.66e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  248 NVIAIEGKDAVLECCVSGYPPPSFTWLR-GEEVIQLRSKK--YSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAE 324
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMKdDNPIVESRRFQidQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                  ...
gi 117168295  325 LTV 327
Cdd:cd20973    86 LTV 88

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 49.62 E-value: 3.69e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   45 EPSDAVTMRGGNVLLNCSAEsdrGV--PVIKWKKD-----GLILALGMDDRKQQLPNGSLLIQNIlhsrhHKPDEGLYQC 117
Cdd:cd20954     7 EPVDANVAAGQDVMLHCQAD---GFptPTVTWKKAtgstpGEYKDLLYDPNVRILPNGTLVFGHV-----QKENEGHYLC 78

                          90
                  ....*....|....*....
gi 117168295  118 EASlADSGSIISRTAKVTV 136
Cdd:cd20954    79 EAK-NGIGSGLSKVIFLKV 96

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 49.49 E-value: 3.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  339 NLYAYESMDIEFECAVSGKPVPTVNWMKNGDVvIPSDYFQIVGgSN--LRILGVVK-SDEGFYQCVAENEAGN-AQSSAQ 414
Cdd:cd20958     9 NLTAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPLNHRQRVF-PNgtLVIENVQRsSDEGEYTCTARNQQGQsASRSVF 86


                  ...
gi 117168295  415 LIV 417
Cdd:cd20958    87 VKV 89

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 49.21 E-value: 3.87e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  241 YFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSL-LGGSNLLISNVTDDDSGTYTCVVTYKNENI 319
Cdd:cd05868     1 YWITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRkVDGDTIIFSKVQERSSAVYQCNASNEYGYL 80


                  ....*....
gi 117168295  320 SASAELTVL 328
Cdd:cd05868    81 LANAFVNVL 89

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 49.33 E-value: 3.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  148 SITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPgDSRVVVLP-SGALQIS-------RLQpgdsGVYRCSARNPAS 219
Cdd:cd05733    10 DYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAK-DPRVSMRRrSGTLVIDnhnggpeDYQ----GEYQCYASNELG 84

                          90
                  ....*....|
gi 117168295  220 IRTGNEAEVR 229
Cdd:cd05733    85 TAISNEIRLV 94

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 49.18 E-value: 5.02e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSN-LYAYESMD--IEFECAVSGKPVPTVNW-MKNGDVVIPSDYFQIVGGsNLRILGVVKS-DEGFYQCVAENE 405
Cdd:cd05849     2 PVFEEQPIDtIYPEESTEgkVSVNCRARANPFPIYKWrKNNLDIDLTNDRYSMVGG-NLVINNPDKYkDAGRYVCIVSNI 80


                  ....*..
gi 117168295  406 AGNAQSS 412
Cdd:cd05849    81 YGKVRSR 87

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 48.38 E-value: 6.51e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    846 PPVGVQAVALTHEAVRVSWadNSVPKNQKTSDVRLYTVRWRTSFSASAKYkSEDTTSLSYTATGLKPNTMYEFSVMVTKN 925
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSW--EPPPDDGITGYIVGYRVEYREEGSEWKEV-NVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 117168295    926 RRSS 929
Cdd:smart00060   80 AGEG 83

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 48.54 E-value: 9.20e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd20969    17 GHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAAN 79

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 48.16 E-value: 9.48e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295   43 VSEPSDAVTMRGGNVLLNCSAESDRgVPVIKWKKDGLILALGmddRKQQLPNGSLLIQNILHSrhhkpDEGLYQCEA 119
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDP-VPTVRWRKEDGELPKG---RYEILDDHSLKIRKVTAG-----DMGSYTCVA 68

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 48.39 E-value: 9.55e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   42 FVSEPSDAVTMRG---GNVLLNCSAESDRgVPVIKWKKDGLILALGMDDRkQQLPNGSLLIQNILHSRhhkpDEGLYQCE 118
Cdd:cd04967     4 FEEQPDDTIFPEDsdeKKVALNCRARANP-VPSYRWLMNGTEIDLESDYR-YSLVDGTLVISNPSKAK----DAGHYQCL 77

                          90
                  ....*....|....*....
gi 117168295  119 ASLAdSGSIISRTAKVTVA 137
Cdd:cd04967    78 ATNT-VGSVLSREATLQFG 95

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 48.41 E-value: 1.03e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  242 FLQRPSNVI----AIEGKdAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGsNLLISNV-TDDDSGTYTCVVT 313
Cdd:cd05849     4 FEEQPIDTIypeeSTEGK-VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGG-NLVINNPdKYKDAGRYVCIVS 78

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 48.27 E-value: 1.11e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  144 SQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNqqDLNPLPGDSRVVVLPSGA-LQISRLQPGDSGVYRCSARNPA 218
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRN--GNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGV 80

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 47.97 E-value: 1.14e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLrSKKYSLL--GGS--NLLISNVTDDDSGTYTCVVtyKNENISA 321
Cdd:cd05737     8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAF-LDHCNLKveAGRtvYFTINGVSSEDSGKYGLVV--KNKYGSE 84


                  ....*...
gi 117168295  322 SAELTVLV 329
Cdd:cd05737    85 TSDVTVSV 92

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 48.39 E-value: 1.15e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSN-LYAYESMD--IEFECAVSGKPVPTVNW-MKNGDVVIPSDY-FQIVGGsNLRILGVVKS-DEGFYQCVAEN 404
Cdd:cd04967     2 PVFEEQPDDtIFPEDSDEkkVALNCRARANPVPSYRWlMNGTEIDLESDYrYSLVDG-TLVISNPSKAkDAGHYQCLATN 80


                  ....*..
gi 117168295  405 EAGNAQS 411
Cdd:cd04967    81 TVGSVLS 87

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 48.17 E-value: 1.23e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  347 DIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSNLRIL------GVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05733    18 NITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRRSGTLvidnhnGGPEDYQGEYQCYASNELGTAISNEIRLV 94

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 47.48 E-value: 1.27e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNqqdLNPLPGDSRVVVLPS---GALQISRLQPGDSGVYRCSARN 216
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLN---WGHVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAIN 63

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 47.84 E-value: 1.28e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  148 SITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNplpGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd04969    11 KILAAKGGDVIIECKPKASPKPTISWSKGTELLT---NSSRICILPDGSLKIKNVTKSDEGKYTCFAVN 76

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 48.02 E-value: 1.29e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLpSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAG-VGELHIQDVLPEDHGTYTCLAKNAA 79

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 47.78 E-value: 1.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIP-SDYFQIV----GGSNLRILGVVKSDEGFYQCVAENE 405
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPkSDHYTIQrdldGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 117168295  406 AGNAQSSAQLIV 417
Cdd:cd05893    81 QGRISCTGRLMV 92

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 47.61 E-value: 1.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  349 EFECAVSGKPVPTVNWMKNGDVVIPS------------DYFQIVggsNLRIlgvvkSDEGFYQCVAENEAGNAQSSAQLI 416
Cdd:cd05763    18 RLECAATGHPTPQIAWQKDGGTDFPAarerrmhvmpedDVFFIV---DVKI-----EDTGVYSCTAQNSAGSISANATLT 89


                  .
gi 117168295  417 V 417
Cdd:cd05763    90 V 90

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 47.56 E-value: 1.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   54 GGNVLLNCSAEsdrGVPV--IKWKKDGLILALgmdDRKQQL-PNGSLLIQNIlhsrHHKPDEGLYQCEASlADSGSIISR 130
Cdd:cd20958    15 GQTLRLHCPVA---GYPIssITWEKDGRRLPL---NHRQRVfPNGTLVIENV----QRSSDEGEYTCTAR-NQQGQSASR 83


                  ....*.
gi 117168295  131 TAKVTV 136
Cdd:cd20958    84 SVFVKV 89

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 47.74 E-value: 1.73e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQdlnPLPGDSRVVVLPS---GALQISRLQPGDSGVYRCSAR 215
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ---IIVSSQRHQITSTeykSTFEISKVQMSDEGNYTVVVE 79


                  .
gi 117168295  216 N 216
Cdd:cd05747    80 N 80

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 47.14 E-value: 2.25e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVI-----QLRSKKYSLLggSNLLISNVTDDDSGTYTcvVTYKNENIS 320
Cdd:cd05894     2 ENTIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFtategRVRVESYKDL--SSFVIEGAEREDEGVYT--ITVTNPVGE 77


                  ....*....
gi 117168295  321 ASAELTVLV 329
Cdd:cd05894    78 DHASLFVKV 86

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 47.31 E-value: 2.26e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKN-GDvvIPSDYFQIVGGSNLRILG--------VVKSDEGFYQC 400
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAtGS--TPGEYKDLLYDPNVRILPngtlvfghVQKENEGHYLC 78


                  ....*..
gi 117168295  401 VAENEAG 407
Cdd:cd20954    79 EAKNGIG 85

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 51.87 E-value: 2.95e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  385 LRILGVVKSDEGFY--QCVAENEAGNAQSSAQLIVP-KPAIPSSSILPSAPRDVLPVLVSSRFVRLSWRPPAEAkgniQT 461
Cdd:COG4733   491 FRVVSIEENEDGTYtiTAVQHAPEKYAAIDAGAFDDvPPQWPPVNVTTSESLSVVAQGTAVTTLTVSWDAPAGA----VA 566

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  462 FTVFFSREGDNRERALNTTQPGS--LQLTVGNlkpeamYTFRVVAYNEWG-PGESSQPIKVATQPELQVPGPVENLHAVS 538
Cdd:COG4733   567 YEVEWRRDDGNWVSVPRTSGTSFevPGIYAGD------YEVRVRAINALGvSSAWAASSETTVTGKTAPPPAPTGLTATG 640

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  539 tSPTSILITWEPPAYAngPVQGYRLFCTEVSTGKEQNIEVD---GLSYKLEGLKKFTEYTLRFLAYNRYG-------PGV 608
Cdd:COG4733   641 -GLGGITLSWSFPVDA--DTLRTEIRYSTTGDWASATVAQAlypGNTYTLAGLKAGQTYYYRARAVDRSGnvsawwvSGQ 717


                  ....*
gi 117168295  609 STDDI 613
Cdd:COG4733   718 ASADA 722

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 46.63 E-value: 3.01e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  146 TESITAFMGDTVLLKCEVIGEPMPTIHWQKnqqDLNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARNP 217
Cdd:cd05731     2 ESSTMVLRGGVLLLECIAEGLPTPDIRWIK---LGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNT 70

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 46.78 E-value: 3.27e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  352 CAVSGKPVPTVNWMKNGDVVIPSDYFQIvgGSNLRILGVVKS----------DEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20956    23 CVASGNPLPQITWTLDGFPIPESPRFRV--GDYVTSDGDVVSyvnissvrveDGGEYTCTATNDVGSVSHSARINV 96

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 46.58 E-value: 3.91e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQL----RSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd20974     3 FTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTstlpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSG 82

                          90
                  ....*....|.
gi 117168295  318 NISASAELTVL 328
Cdd:cd20974    83 QATSTAELLVL 93

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 46.03 E-value: 4.80e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   337 PSNLYAYESMDIEFECAVS-GKPVPTVNWMKNGDVVIPSDYFQI----VGGSNLRILGVVKSDEGFYQCVAENEAGNAQS 411
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHdngrTTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82


                   ....
gi 117168295   412 SAQL 415
Cdd:pfam00047   83 STSL 86

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 46.09 E-value: 5.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSN-LYAYESMD--IEFECAVSGKPVPTVNWMKNG-DVVIPSDY-FQIVGGSNLRILGVVKSDEGFYQCVAENE 405
Cdd:cd05848     2 PVFVQEPDDaIFPTDSDEkkVILNCEARGNPVPTYRWLRNGtEIDTESDYrYSLIDGNLIISNPSEVKDSGRYQCLATNS 81


                  ....*.
gi 117168295  406 AGNAQS 411
Cdd:cd05848    82 IGSILS 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.46 E-value: 7.80e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295   147 ESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNplpgdsrvvvlPSGALQISRLQPGDSGVYRCSARNPA 218
Cdd:pfam13895    7 SPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS-----------SSPNFFTLSVSAEDSGTYTCVARNGR 67

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 45.27 E-value: 8.31e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  249 VIAIEGKDAVLECCVSGYPPPSFTWLRGEEVI------QLRSKKYSllggSNLLISNVTDDDSGTYTcvVTYKNENISAS 322
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLketgrvQIETTASS----TSLVIKNAKRSDSGKYT--LTLKNSAGEKS 75


                  ....*..
gi 117168295  323 AELTVLV 329
Cdd:cd05748    76 ATINVKV 82

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 45.38 E-value: 8.54e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  249 VIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIqLRSKKYSLLGGSNLLISNVTDDDSGTYTC 310
Cdd:cd05852    12 ILAAKGGRVIIECKPKAAPKPKFSWSKGTELL-VNNSRISIWDDGSLEILNITKLDEGSYTC 72

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 45.72 E-value: 9.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  333 FLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVI--------PSDYFQIVGGSNLRILGVVKSDEGFYQCVAEN 404
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqppqPSSRFSVSPTGDLTITNVQRSDVGYYICQALN 81

                          90
                  ....*....|...
gi 117168295  405 EAGNAQSSAQLIV 417
Cdd:cd05726    82 VAGSILAKAQLEV 94

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 45.24 E-value: 1.06e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  259 LECCVSGYPPPSFTWLRG------EEVIQLRSKKYSLLggsnllISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd05856    24 LKCVASGNPRPDITWLKDnkpltpPEIGENKKKKWTLS------LKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 45.29 E-value: 1.08e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  348 IEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGSN----LRILGVVKSDEGFYQCVAENEAG 407
Cdd:cd05729    22 VRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEkgwsLIIERAIPRDKGKYTCIVENEYG 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 45.10 E-value: 1.19e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295   846 PPVGVQAVALTHEAVRVSWAdnsvPKNQKTSDVRLYTVRWRTSFSASA-KYKSEDTTSLSYTATGLKPNTMYEFSV 920
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWT----PPPDGNGPITGYEVEYRPKNSGEPwNEITVPGTTTSVTLTGLKPGTEYEVRV 73

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 49.94 E-value: 1.27e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  622 PSAPPQNI----SLEVVNS----RSIKVSWLPPPSGTqngfitGYKIRHRK--TTRRGEMETLEPNnlwYLFTGLEKGsQ 691
Cdd:COG4733   529 PQWPPVNVttseSLSVVAQgtavTTLTVSWDAPAGAV------AYEVEWRRddGNWVSVPRTSGTS---FEVPGIYAG-D 598

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  692 YSFQVSAmtVNGTGPPSNWytAETPENDLD-ESQVPDQPSSLHVRPQTNCIIMSWTPPLNPNivVRGYIIGYGVGSPY-- 768
Cdd:COG4733   599 YEVRVRA--INALGVSSAW--AASSETTVTgKTAPPPAPTGLTATGGLGGITLSWSFPVDAD--TLRTEIRYSTTGDWas 672

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  769 AETVRVDSKQRYYSIERLESSSHYVISLKAFNNAGEGVPLYESATT--------RSITDPTDPVDYYPLLDDF--PTSGP 838
Cdd:COG4733   673 ATVAQALYPGNTYTLAGLKAGQTYYYRARAVDRSGNVSAWWVSGQAsadaagilDAITGQILETELGQELDAIiqNATVA 752

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  839 DVSTPMLPPVGVQAVALTHEAVRVSWADNSVPKNQKTSDVRLYTVRWRTS-FSASAKYKSEDTTSLSYTATGLKPNTMYE 917
Cdd:COG4733   753 EVVAATVTDVTAQIDTAVLFAGVATAAAIGAEARVAATVAESATAAAATGtAADAAGDASGGVTAGTSGTTGAGDTAAST 832

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  918 FSVMVTKNRRSSTWSMTAHATTYEAAPTSAPKDLTVITREGKPRAVIVSWQPPLEANGKITAYILFYTLDKNIPIDDWIM 997
Cdd:COG4733   833 TRVAAAVVLAGVVVYGDAIIESGNTGDIVATGDIASAAAGAVATTVSGTTAADVSAVADSTAASLTAIVIAATTIIDAIG 912


                  ....*.
gi 117168295  998 ETISGD 1003
Cdd:COG4733   913 DGTTRE 918

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 45.35 E-value: 1.34e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  155 DTVLLKCEVIGEPMPTIHWQKNQQDLNpLPGDSRVVVLP-SGALQI---SRLQPGD-SGVYRCSARN 216
Cdd:cd05875    17 DNILIECEAKGNPVPTFHWTRNGKFFN-VAKDPRVSMRRrSGTLVIdfrGGGRPEDyEGEYQCFARN 82

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 45.00 E-value: 1.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNqqdLNPLPGDSR-------VVVLPSGALQISRLQPGDSGVYR 211
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKA---TGSTPGEYKdllydpnVRILPNGTLVFGHVQKENEGHYL 77


                  ....*
gi 117168295  212 CSARN 216
Cdd:cd20954    78 CEAKN 82

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 44.86 E-value: 1.64e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQknqQDLNPLPGDSRV----VVLPSGA----LQISRLQPGDSGVYRCSARNPAS 219
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWT---LDGFPIPESPRFrvgdYVTSDGDvvsyVNISSVRVEDGGEYTCTATNDVG 86

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 44.76 E-value: 1.79e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  141 RFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDL--NPlpgdSRVVVLPSGALQISRLQPG----DSGVYRCSA 214
Cdd:cd05892     2 MFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqyNT----DRISLYQDNCGRICLLIQNankkDAGWYTVSA 77

                          90
                  ....*....|
gi 117168295  215 RNPASIRTGN 224
Cdd:cd05892    78 VNEAGVVSCN 87

104 kDa microneme/rhoptry antigen; Provisional

Pssm-ID: 185628 [Multi-domain] Cd Length: 943 Bit Score: 49.30 E-value: 1.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1142 KGSQKDLRPPDlwihhEEMEMKNIEKPTGTDPAGrdspiqscqdLTPVSHSQSETQMGSKSASHSGQDTEDAGSSMSTLE 1221
Cdd:PTZ00449  490 KKSKKKLAPIE-----EEDSDKHDEPPEGPEASG----------LPPKAPGDKEGEEGEHEDSKESDEPKEGGKPGETKE 554

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1222 RSLAARratraklmiPMEAQSSNPavvSAIPVPTlESAQYPGILPSPTcGYPHPQFTLRPVpfptlsvdrgfgagrtqsV 1301
Cdd:PTZ00449  555 GEVGKK---------PGPAKEHKP---SKIPTLS-KKPEFPKDPKHPK-DPEEPKKPKRPR------------------S 602

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1302 SEGPTTQQQPMLP-----PAQPEHPSSEEAPSRTIPTAcvRPTHPLRSFANPLLPPPMSAIEPKVPYTPLL--------- 1367
Cdd:PTZ00449  603 AQRPTRPKSPKLPelldiPKSPKRPESPKSPKRPPPPQ--RPSSPERPEGPKIIKSPKPPKSPKPPFDPKFkekfyddyl 680

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1368 -----SQPGPTLPKTHVKTASLGLAGKARSPLLPVSV-----PTAPEVSEESHKPTEDPASvyEQDDLSE 1427
Cdd:PTZ00449  681 daaakSKETKTTVVLDESFESILKETLPETPGTPFTTprplpPKLPRDEEFPFEPIGDPDA--EQPDDIE 748

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 49.55 E-value: 1.95e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1168 PTGTDPAGRDSPIQScqdltPVSHSQSETQMGSKSASHSGQDTED-AGSSMSTLERSLAARRATRAKlmIPMEAQSSNPA 1246
Cdd:PHA03247 2616 PLPPDTHAPDPPPPS-----PSPAANEPDPHPPPTVPPPERPRDDpAPGRVSRPRRARRLGRAAQAS--SPPQRPRRRAA 2688

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1247 VVSAIPVPTLESAQYPGILPSPTcgyPHPQFTLRPVPFPTLSVDRGFGAGRTQSVSegPTTQQQPMLP--PAQPEHPSSE 1324
Cdd:PHA03247 2689 RPTVGSLTSLADPPPPPPTPEPA---PHALVSATPLPPGPAAARQASPALPAAPAP--PAVPAGPATPggPARPARPPTT 2763

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1325 EAPSRTIPTAcVRPTHPLRSfanpLLPPPMSAIEPKVPYTPLLSQPGPTLPKTHVKTASLGLAGKARSPLLP--VSVPTA 1402
Cdd:PHA03247 2764 AGPPAPAPPA-APAAGPPRR----LTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPptSAQPTA 2838

                         250
                  ....*....|....
gi 117168295 1403 PEVSEESHKPTEDP 1416
Cdd:PHA03247 2839 PPPPPGPPPPSLPL 2852

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 43.71 E-value: 2.00e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  157 VLLKCEVIGEPMPTIHWQKNQQDLNPlpgDSRVVVLPSGALQISRLQPGDSGVYRCSARNP 217
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTE---SGKFHISPEGYLAIRDVGVADQGRYECVARNT 58

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 44.50 E-value: 2.02e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  241 YFLQRPSNVIAIEGKDAVLECCVSGYPPPSFTW-LRGEEVIQLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENI 319
Cdd:cd05867     1 YWTRRPQSHLYGPGETARLDCQVEGIPTPNITWsINGAPIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80


                  ....*....
gi 117168295  320 SASAELTVL 328
Cdd:cd05867    81 LANAHVHVV 89

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 44.85 E-value: 2.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPP--SFTWLRGEEVIQLR------SKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd04970     9 PSNADITVGENATLQCHASHDPTLdlTFTWSFNGVPIDLEkieghyRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                          90
                  ....*....|....
gi 117168295  318 NISASAELTVLVPP 331
Cdd:cd04970    89 SDSASATLVVRGPP 102

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 44.13 E-value: 2.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  247 SNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYsLLGGSNLLISNVTDDDSGTYTCVVtyKNENISASAELT 326
Cdd:cd05876     3 SSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKY-QNHNKTLQLLNVGESDDGEYVCLA--ENSLGSARHAYY 79


                  ...
gi 117168295  327 VLV 329
Cdd:cd05876    80 VTV 82

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 49.17 E-value: 2.45e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1168 PTGTDPAGRDSPIQScqdLTPVSHSQSETQMGSKSASHSGQDTEDAGSSMSTLERSLAA---RRATR--------AKLMI 1236
Cdd:PHA03247 2722 PPGPAAARQASPALP---AAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAgppRRLTRpavaslseSRESL 2798

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1237 PMEAQSSNPAVVSAIPVPTLESAQYP-GILPSPTCGYPHPQFTLRPVPFPTLSVDRGFGAGrtQSVSEGPTTQQQPMLPp 1315
Cdd:PHA03247 2799 PSPWDPADPPAAVLAPAAALPPAASPaGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPG--GDVRRRPPSRSPAAKP- 2875

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295 1316 AQPEHPS----SEEAPSRTIPTACVRPTHPLRSFANPLLPPPMSAIEPKVPYTPllsQPGPT--------LPKTHVKTAS 1383
Cdd:PHA03247 2876 AAPARPPvrrlARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQP---QPPPPppprpqppLAPTTDPAGA 2952

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 117168295 1384 LGLAGKARSPLLPVSVPTAPEVSE----ESHKPTEDPAS 1418
Cdd:PHA03247 2953 GEPSGAVPQPWLGALVPGRVAVPRfrvpQPAPSREAPAS 2991

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 44.02 E-value: 2.78e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  142 FLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVlPSG--ALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVR-ENGrhSLIIEPVTKRDAGIYTCIARNRA 80

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 44.15 E-value: 2.82e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  156 TVLLKCEVIGEPMPTIHWQKnqqDLNPLPGDSRVVVLPSG--ALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05760    18 RVTLRCHIDGHPRPTYQWFR---DGTPLSDGQGNYSVSSKerTLTLRSAGPDDSGLYYCCAHNAF 79

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 44.40 E-value: 3.02e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  329 VPPWFLNHPSNLYAYESMDIEFECAVSG-KPVpTVNWMKNGDVVIPSDYFQIVGG---------SNLRILGVVKSDEGFY 398
Cdd:cd05735     2 IPAMITSYPNTTLATKGQKKEMSCTAHGeKPI-IVRWEKEDTIINPSEMSRYLVTtkevgdeviSTLQILPTVREDSGFF 80

                          90
                  ....*....|....*....
gi 117168295  399 QCVAENEAGNAQSSAQLIV 417
Cdd:cd05735    81 SCHAINSYGEDRGIIQLTV 99

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 44.00 E-value: 3.34e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVViPSDYFQIV-----GGSNLRILGV-VKSDEGFYQCVAEN 404
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEI-IADGLKYRiqefkGGYHQLIIASvTDDDATVYQVRATN 80

                          90
                  ....*....|...
gi 117168295  405 EAGNAQSSAQLIV 417
Cdd:cd20971    81 QGGSVSGTASLEV 93

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.54 E-value: 3.36e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    43 VSEPSDAVTMRGGNVLLNCSAeSDRGVPVIKWKKDGLILAlgmddrkqqlPNGSLLIQNILHSrhhkpDEGLYQCEASLa 122
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSA-PGNPPPSYTWYKDGSAIS----------SSPNFFTLSVSAE-----DSGTYTCVARN- 65

                           90
                   ....*....|....
gi 117168295   123 DSGSIISRTAKVTV 136
Cdd:pfam13895   66 GRGGKVSNPVELTV 79

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.75 E-value: 3.62e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  148 SITAFMGDTVLLKCEVIGEPMPTIHWQKNQqdlNPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05876     4 SLVALRGQSLVLECIAEGLPTPTVKWLRPS---GPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAEN 69

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 43.74 E-value: 3.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLrSKKYSLLGGS----NLLISNVTDDDSGTYTcvVTYKNENISA 321
Cdd:cd05891     8 PDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIEL-SEHYSVKLEQgkyaSLTIKGVTSEDSGKYS--INVKNKYGGE 84


                  ....*...
gi 117168295  322 SAELTVLV 329
Cdd:cd05891    85 TVDVTVSV 92

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.84 E-value: 3.98e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLR--GEEVIQLRSKKY----SLLGGSNLLISNVTDDDSGTYTC 310
Cdd:cd20954     8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPGEYKDLLYdpnvRILPNGTLVFGHVQKENEGHYLC 78

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 43.34 E-value: 5.32e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295   148 SITAFMGDTVLLKCEVI-GEPMPTIHWQKNQQDLNPLPGDSRVVVLPSGA-LQISRLQPGDSGVYRCSARNP 217
Cdd:pfam00047    5 TVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSsLLISNVTKEDAGTYTCVVNNP 76

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 43.30 E-value: 5.72e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117168295  244 QRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEviQLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVtyknENI 319
Cdd:cd04968     6 RFPADTYALKGQTVTLECFALGNPVPQIKWRKVDG--SPSSQWEITTSEPVLEIPNVQFEDEGTYECEA----ENS 75

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 43.32 E-value: 6.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVI----QLRSKKYSLLGG---SNLLISNVTDDDSGTYTCVVTY 314
Cdd:cd20956     4 LLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIpespRFRVGDYVTSDGdvvSYVNISSVRVEDGGEYTCTATN 83

                          90
                  ....*....|...
gi 117168295  315 KNENISASAELTV 327
Cdd:cd20956    84 DVGSVSHSARINV 96

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 42.97 E-value: 7.76e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  149 ITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNplPGDSRVVVLPSG---ALQISRLQPGDSGVYRCSARN 216
Cdd:cd05891    11 VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIE--LSEHYSVKLEQGkyaSLTIKGVTSEDSGKYSINVKN 79

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 42.76 E-value: 8.70e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  253 EGKDAVLECCVSGYPPPSFTWL-RGEEVIQLRSK-KYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILWLsPRKHLVSAKSNgRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.66 E-value: 9.95e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  332 WFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNG--DVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAG 407
Cdd:cd05868     1 YWITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGvpIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYG 78

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 42.38 E-value: 1.05e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  348 IEFECAVSGKPVPTVNWMKNGDVVIPS---DYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20969    20 VQFVCRADGDPPPAILWLSPRKHLVSAksnGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 42.22 E-value: 1.08e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  265 GYPPPSFTWLRGEEVIQLRSKKYSllgGSNLLISNVTDDDSGTYTCVVTYKNENISASAELTVLV 329
Cdd:cd05864    28 GYPPPEIKWYKNGIPIESNHTIKA---GHVLTIMEVTEKDAGNYTVVLTNPISKEKQRHTFSLVV 89

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 42.20 E-value: 1.40e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  251 AIEGKDAV-LECCVSGYPPPSFTWLRGEEVIqlrSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAELTVLV 329
Cdd:cd04976    14 ATAGKRSVrLPMKVKAYPPPEVVWYKDGLPL---TEKARYLTRHSLIIKEVTEEDTGNYTILLSNKQSNVFKNLTATLVV 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 42.18 E-value: 1.49e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  139 PLRFLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGdsrVVVLPSGALQ---ISRLQPGDSGVYRCSAR 215
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPD---IQIHQEGDLHsliIAEAFEEDTGRYSCLAT 77

                          90
                  ....*....|....*
gi 117168295  216 NPASiRTGNEAEVRI 230
Cdd:cd20972    78 NSVG-SDTTSAEIFV 91

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1). VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-1 binds VEGF-A strongly; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409499 Cd Length: 92 Bit Score: 42.17 E-value: 1.62e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  263 VSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSnLLISNVTDDDSGTYTCVVTYKNENISASAELTVLV 329
Cdd:cd07702    27 VKAFPSPEVIWLKDGLPATEKCARYLTRGYS-LIIKDVTEEDAGNYTILLSIKQSNLFKNLTATLIV 92

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 41.79 E-value: 1.69e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKnqqDLNPLPGDSRVVVLPSG----ALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd20973    12 GSAARFDCKVEGYPDPEVKWMK---DDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSL 77

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 45.39 E-value: 1.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  150 TAFM---GDTVLLKCEVI-----GEPMPTIHWQKNQQDlnplpgDSRVVVLPSGA-LQISRLQPGDSGVYRCSARNPA-- 218
Cdd:PHA02785   34 ASFMeleNEPVILPCPQIntlssGYNILDILWEKRGAD------NDRIIPIDNGSnMLILNPTQSDSGIYICITKNETyc 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  219 -------SIRTGNEAEVRILSDPGL--HRQLYFLQRPsNVIAIEGKDAVLECCVSGYPppsftwlrgeeviQLRSKKYSL 289
Cdd:PHA02785  108 dmmslnlTIVSVSESNIDLISYPQIvnERSTGEMVCP-NINAFIASNVNADIIWSGHR-------------RLRNKRLKQ 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  290 LGGSNLLISNVTDDDSGTYTCVVTY----KNENISASAELTV---LVPPwFLNHPSNLYAYESMDIEFECAVSGKPvPTV 362
Cdd:PHA02785  174 RTPGIITIEDVRKNDAGYYTCVLKYiygdKTYNVTRIVKLEVrdrIIPP-TMQLPEGVVTSIGSNLTIACRVSLRP-PTT 251

                         250
                  ....*....|
gi 117168295  363 N----WMKNG 368
Cdd:PHA02785  252 DadvfWISNG 261

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 41.73 E-value: 1.90e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  353 AVSGKPVPTVNWMKNGDVV--IPSDYFQIVGG---SNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd05750    23 ATSENPSPRYRWFKDGKELnrKRPKNIKIRNKkknSELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 41.54 E-value: 2.01e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  352 CAVSGKPVPTVNWMKNG---DVVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSS-AQLIV 417
Cdd:cd05738    21 CAASGNPDPEISWFKDFlpvDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSApANLYV 90

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 46.09 E-value: 2.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  840 VSTPMLPPVGVQAVALTheaVRVSWADNSVpkNQKTSDVRLyTVRWRTS---FSASAKYKSED--------TTSLSYTAT 908
Cdd:COG4733   519 IDAGAFDDVPPQWPPVN---VTTSESLSVV--AQGTAVTTL-TVSWDAPagaVAYEVEWRRDDgnwvsvprTSGTSFEVP 592

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  909 GLKPNTmYEFSVM-VTKNRRSSTWSMTAHAT-TYEAAPTSAPKDLTVitrEGKPRAVIVSWQPPLEANgkITAYILFYTL 986
Cdd:COG4733   593 GIYAGD-YEVRVRaINALGVSSAWAASSETTvTGKTAPPPAPTGLTA---TGGLGGITLSWSFPVDAD--TLRTEIRYST 666

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 117168295  987 DknipiDDW---IMETISGDRLTHQIMDLSLDTMYYFRIQARNVKG 1029
Cdd:COG4733   667 T-----GDWasaTVAQALYPGNTYTLAGLKAGQTYYYRARAVDRSG 707

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 41.89 E-value: 2.09e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  147 ESITAF-MGDTVLLKCEVIGEPMPTIHWQKNQQDL--NPLPGDSRVVVLPS---GALQISRLQPGDSGVYRCSARNP 217
Cdd:cd05869     9 ENQTAMeLEEQITLTCEASGDPIPSITWRTSTRNIssEEKTLDGHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNT 85

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 2.22e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    44 SEPSDAVTMRGGNVLLNCSAESDRGVPVIKWKKDGLILALGMDDRKQQLPNG--SLLIQNIlhsrhHKPDEGLYQCEASL 121
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqsSLLISNV-----TKEDAGTYTCVVNN 75

                           90
                   ....*....|
gi 117168295   122 ADSGSIISRT 131
Cdd:pfam00047   76 PGGSATLSTS 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 41.82 E-value: 2.30e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  259 LECCVSGYPPPSFTWLR-GEEVIQ--------LRSKKYSLLggsnllISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd05729    24 LECGAGGNPMPNITWLKdGKEFKKehriggtkVEEKGWSLI------IERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 40.69 E-value: 2.71e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  253 EGKDAVLECCVSGYPPPSFTWLRGEEVIQLrSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSV-DRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 41.32 E-value: 2.75e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  352 CAVSGKPVP-TVNWMKNGDVvIPSDY---FQIVG--GSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIV 417
Cdd:cd20959    24 CGVPGGDLPlNIRWTLDGQP-ISDDLgitVSRLGrrSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 41.12 E-value: 3.08e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  347 DIEFECAVSGKPVPTVNWMKNGDVV-IPSDYFQIV----GGSNLRILGVVKSD--EGFYQCVAENEAGNAQSS 412
Cdd:cd05874    18 NIVIQCEAKGKPPPSFSWTRNGTHFdIDKDPKVTMkpntGTLVINIMNGEKAEayEGVYQCTARNERGAAVSN 90

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 40.56 E-value: 3.70e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKkysllggsnLLISNVTDDDSGTYTCVV 312
Cdd:cd20948     2 PSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQE---------LFLPAITENNEGTYTCSA 59

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 44.76 E-value: 4.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1165 IEKPTGTDPAGRDSPIQSCQ------DLTPVSHSQSETQMGSKSASHSGQDTEDAGSSMSTLERSLAARRATRAKLMIPM 1238
Cdd:pfam03154  289 MQHPVPPQPFPLTPQSSQSQvppgpsPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIPQLPN 368

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1239 EAQSSNPAVVSAiPVPTlesaQYPGILPSPTCGYP-------HPQfTLRPVPFPTLSVDRGFGAGRTQSvsegPTTQQQP 1311
Cdd:pfam03154  369 PQSHKHPPHLSG-PSPF----QMNSNLPPPPALKPlsslsthHPP-SAHPPPLQLMPQSQQLPPPPAQP----PVLTQSQ 438

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1312 MLPPAQPEHPSSeeAPSRTIPTACVRPTHPLRSFANPLLPPP----------MSAIEPKVPYTPLLSQPGP-----TLPK 1376
Cdd:pfam03154  439 SLPPPAASHPPT--SGLHQVPSQSPFPQHPFVPGGPPPITPPsgpptstssaMPGIQPPSSASVSSSGPVPaavscPLPP 516

                          250       260
                   ....*....|....*....|....*..
gi 117168295  1377 THVKTASLGLAGKARSPLLPVSVPTAP 1403
Cdd:pfam03154  517 VQIKEEALDEAEEPESPPPPPRSPSPE 543

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.

Pssm-ID: 465220 [Multi-domain] Cd Length: 93 Bit Score: 40.47 E-value: 5.12e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   860 VRVSWADNSVPKNQKtsdVRLYTVRWRTSFSASAK------YKSEDTTSLSYTATGLKPNTMYEFSVMVTknrrSSTWSM 933
Cdd:pfam16656   15 MTVSWVTPSAVTSPV---VQYGTSSSALTSTATATsstyttGDGGTGYIHRATLTGLEPGTTYYYRVGDD----NGGWSE 87


                   ....*.
gi 117168295   934 TAHATT 939
Cdd:pfam16656   88 VYSFTT 93

Interferon-alpha/beta receptor, fibronectin type III; Members of this family adopt a secondary structure consisting of seven beta-strands arranged in an immunoglobulin-like beta-sandwich, in a Greek-key topology. They are required for binding to interferon-alpha.

Pssm-ID: 462746 Cd Length: 103 Bit Score: 40.79 E-value: 5.20e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   625 PPQnISLEVVNsRSIKVSWLPPPSGTQNGFIT-------GYKIRHRKTTRRGEMETLEPNNLWYLFTGLEKGSQYSFQVS 697
Cdd:pfam09294    5 PPE-VELEVEG-GSLNVTVKDPETREGKNLSLrdlygslQYRVSYWKNSSNGEKKNTTSTNSFVVLSDLEPGTTYCVSVQ 82

                           90       100
                   ....*....|....*....|.
gi 117168295   698 A--MTVNGTGPPSNWYTAETP 716
Cdd:pfam09294   83 AfsPLDNKSSQRSPPQCIRTT 103

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.54 E-value: 5.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIV-GGSNLRILGVVKSDEGFYQCVAENEAGNA 409
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVyDNGTLDILITTVKDTGAFTCIASNPAGEA 80


                  ....*...
gi 117168295  410 QSSAQLIV 417
Cdd:cd05764    81 TARVELHI 88

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 40.52 E-value: 5.54e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  147 ESITAFMGDTVLLKCEVIGEPMPtIHWQKNQQDLnPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd04979     4 KQISVKEGDTVILSCSVKSNNAP-VTWIHNGKKV-PRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGE 71

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 40.65 E-value: 5.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  137 AGPLRFLSQTESITAFMGDTVLLKCEvIGEPMPTIHWQKNQQdlnPLPGDSRVVVLPSgALQISRLQPGDSGVYRCSARN 216
Cdd:cd04973     7 APPTYQISEVESYSAHPGDLLQLRCR-LRDDVQSINWTKDGV---QLGENNRTRITGE-EVQIKDAVPRDSGLYACVTSS 81


                  ....*.
gi 117168295  217 PASIRT 222
Cdd:cd04973    82 PSGSDT 87

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 40.14 E-value: 6.26e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295   53 RGGNVLLNCSAESDRGvPVIKWKKDGLILALGmdDRKQQLPNGSLLIQNIlhsrhHKPDEGLYQCEAS 120
Cdd:cd04969    16 KGGDVIIECKPKASPK-PTISWSKGTELLTNS--SRICILPDGSLKIKNV-----TKSDEGKYTCFAV 75

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 40.55 E-value: 6.71e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  330 PPWFLNHPSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDY--------FQIVGGSNLRILGVVKSDEGFYQCV 401
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQhivplngrIQLLSNGSLLIKHVLEEDSGYYLCK 80


                  ....*.
gi 117168295  402 AENEAG 407
Cdd:cd05734    81 VSNDVG 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.69 E-value: 7.21e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295   352 CAVSGKPVPTVNWMKNGDVVIPSdyfqivggSNLRILGVVKSDEGFYQCVAENEAGNAQS-SAQLIV 417
Cdd:pfam13895   21 CSAPGNPPPSYTWYKDGSAISSS--------PNFFTLSVSAEDSGTYTCVARNGRGGKVSnPVELTV 79

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

Pssm-ID: 409538 Cd Length: 102 Bit Score: 40.21 E-value: 7.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  249 VIAIEGKDAVLECCVSGYPP-PSFTW-LRGEEV---------IQLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTYKNE 317
Cdd:cd20946     9 VTVVENQEVILSCKTPKKTSsPRVEWkKLQRDVtfvvfqnnkIQGDYKGRAEILGTNITIKNVTRSDSGKYRCEVSARSD 88

                          90
                  ....*....|....
gi 117168295  318 NIS---ASAELTVL 328
Cdd:cd20946    89 GQNlgeVTVTLEVL 102

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 40.20 E-value: 7.94e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  339 NLYAYESMDIEFECAVSGKPVPTVNWMK------------NGDVVIPSDYfqivGGSNLRILGVVKSDEGFYQCVAENEA 406
Cdd:cd05732    10 NQTAVELEQITLTCEAEGDPIPEITWRRatrgisfeegdlDGRIVVRGHA----RVSSLTLKDVQLTDAGRYDCEASNRI 85

                          90
                  ....*....|.
gi 117168295  407 GNAQSSAQLIV 417
Cdd:cd05732    86 GGDQQSMYLEV 96

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 39.90 E-value: 8.25e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLPSG-ALQISRLQPGDSGVYRCSARN 216
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVEN 82

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.

Pssm-ID: 465220 [Multi-domain] Cd Length: 93 Bit Score: 39.70 E-value: 9.47e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   626 PQNISLEVVN-SRSIKVSWLPPPSGTQNGFITGYKIRHRKTTRRGEMETLEPNNLW------YLFTGLEKGSQYSFQVSA 698
Cdd:pfam16656    1 PEQVHLSLTGdSTSMTVSWVTPSAVTSPVVQYGTSSSALTSTATATSSTYTTGDGGtgyihrATLTGLEPGTTYYYRVGD 80

                           90
                   ....*....|....*..
gi 117168295   699 mtvnGTGPPSNWYTAET 715
Cdd:pfam16656   81 ----DNGGWSEVYSFTT 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 39.96 E-value: 9.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  143 LSQTESITAFMGDTVLLKCEVIGEPMPTIHWQK-------NQQDLNPlpgDSRVVV---LPSGALQISRLQPGDSGVYRC 212
Cdd:cd05870     5 IIQLKNETTVENGAATLSCKAEGEPIPEITWKRasdghtfSEGDKSP---DGRIEVkgqHGESSLHIKDVKLSDSGRYDC 81


                  ..
gi 117168295  213 SA 214
Cdd:cd05870    82 EA 83

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 39.41 E-value: 1.04e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 117168295  273 WLRGEEVIQLRSKKYSLLGGsNLLISNVTDDDSGTYTCVVTYKNEN 318
Cdd:cd05873    29 WKFQGKVLKAESPKYGLYGD-GLLIFNASEADAGRYQCLSVEKSKA 73

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 39.92 E-value: 1.07e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  150 TAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNplPGDSRVVVLPSGA-LQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIE--SGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKA 81

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 39.45 E-value: 1.10e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295   43 VSEPSDAVTMRGGNVLLNCSAESDRgVPVIKWKKdglilALGMDDRKQQL--PNGSLLIQNIlhsrhHKPDEGLYQCEA 119
Cdd:cd04968     5 VRFPADTYALKGQTVTLECFALGNP-VPQIKWRK-----VDGSPSSQWEIttSEPVLEIPNV-----QFEDEGTYECEA 72

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409449 Cd Length: 88 Bit Score: 39.53 E-value: 1.21e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  251 AIEGKDAV-LECCVSGYPPPSFTWLRGEEVIQLRSKKYSllggsnLLISNVTDDDSGTYTCVV 312
Cdd:cd05863    15 ATAGDELVkLPVKVAAYPPPEFQWYKDGKLISGKHSPHS------LQIKDVTEASAGTYTLVL 71

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

Pssm-ID: 409354 Cd Length: 95 Bit Score: 39.75 E-value: 1.22e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  254 GKDAVLECCVSGYPPPS--FTWLRGEEVIQL----------RSKKYSLLggSNLLISNVTDDDSGTYTCVVTY 314
Cdd:cd00098    14 GGKVTLVCLVSGFYPKDitVTWLKNGVPLTSgvstsspvepNDGTYSVT--SSLTVPPSDWDEGATYTCVVTH 84

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 40.01 E-value: 1.28e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  143 LSQTE-SITAFMGDTVLLKCEVIGE-PMPTIHWQKNQQDLNP------LPGDSRVVVLPSG------------ALQISRL 202
Cdd:cd00099     1 VTQSPrSLSVQEGESVTLSCEVSSSfSSTYIYWYRQKPGQGPefliylSSSKGKTKGGVPGrfsgsrdgtssfSLTISNL 80

                          90
                  ....*....|...
gi 117168295  203 QPGDSGVYRCSAR 215
Cdd:cd00099    81 QPEDSGTYYCAVS 93

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 39.57 E-value: 1.29e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  347 DIEFECAVSGKPVPTVNWMKNGdvvipsDYFQIV-----------GGSNLRILGVVKSD--EGFYQCVAENEAGNAQSS 412
Cdd:cd05875    18 NILIECEAKGNPVPTFHWTRNG------KFFNVAkdprvsmrrrsGTLVIDFRGGGRPEdyEGEYQCFARNKFGTALSN 90

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409586 Cd Length: 94 Bit Score: 39.37 E-value: 1.38e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  269 PSFTWLRGEEVIQLRSKKYSLLGGsNLLISNVTDDDSGTYTCVVTY----KNENISASAELTVLV 329
Cdd:cd20994    31 PKVQWYKDCKPLLLDDKRFAGLES-DLLIFNVTVQDQGNYTCHTSYtymgKQYNISRTISLIVLE 94

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

Pssm-ID: 409574 Cd Length: 107 Bit Score: 39.75 E-value: 1.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  249 VIAIEGKDAVLECCVSGYPPPSFT---WLRGE----------------EVIQLRSKKYSLLGGSN-----LLISNVTDDD 304
Cdd:cd20982     3 YRAEVGHNAYLPCSYTTAAPGNLVpvcWGKGAcpvsycgnvllrtderDVTYQKSSRYQLKGDFSkgdvsLTIENVTLAD 82


                  ....*...
gi 117168295  305 SGTYTCVV 312
Cdd:cd20982    83 SGIYCCRI 90

Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

Pssm-ID: 401645 [Multi-domain] Cd Length: 846 Bit Score: 43.10 E-value: 1.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1238 MEAQSSNPAvvsaiPVPTLESAQYPGILPSPTcgYPHPQFTLRPVPFPTLSVDRGFGAGRTQSVSEGPTTQQQPMLPPAQ 1317
Cdd:pfam09770  203 MRAQAKKPA-----QQPAPAPAQPPAAPPAQQ--AQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPD 275

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  1318 PEHPSSEEAPSRTIPTACVRPTHPLRSFANPLLPPPmsAIEPKVPYTPLLSQPGPTLPKTH 1378
Cdd:pfam09770  276 PAQPSIQPQAQQFHQQPPPVPVQPTQILQNPNRLSA--ARVGYPQNPQPGVQPAPAHQAHR 334

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 39.21 E-value: 1.55e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  147 ESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQdlnPLPGDSRVVVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05852    10 KKILAAKGGRVIIECKPKAAPKPKFSWSKGTE---LLVNNSRISIWDDGSLEILNITKLDEGSYTCFAEN 76

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.03 E-value: 1.55e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  143 LSQTESITAFMGDTVLLKCEVIGE-PMPTIHWQKNQQDLNPL----------PGDSRvvvlpsgaLQISRLQPGDSGVYR 211
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKrpknikirnkKKNSE--------LQINKAKLEDSGEYT 74


                  ....*
gi 117168295  212 CSARN 216
Cdd:cd05750    75 CVVEN 79

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 39.12 E-value: 1.56e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295  344 ESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQIVGGS----NLRILGVVKSDEGFYQCVAENEAG 407
Cdd:cd05891    15 EGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQgkyaSLTIKGVTSEDSGKYSINVKNKYG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 1.57e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  259 LECCVSGYPPPSFTWLR-GEEViqlrsKKYSLLGGS-------NLLISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd05857    24 FRCPAAGNPTPTMRWLKnGKEF-----KQEHRIGGYkvrnqhwSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 39.09 E-value: 1.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESMDIEFECAVSGKPVPT-VNWMKNGD--VVIPSDYFQIVGGSNLRILGVVKSDEGFYQCVAENEAG 407
Cdd:cd20979     1 PVLKEQPAEVLFREGQPTVLECVTEGGDQGVkYSWLKDGKsfNWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAG 80


                  ....*.
gi 117168295  408 NAQSSA 413
Cdd:cd20979    81 VASSRV 86

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 38.81 E-value: 2.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  155 DTVLLKCEVIGEPMPTIHWQKNQQDLNpLPGDSRVVVLP-SGALQISRLQPGDS----GVYRCSARNPASIRTGNEAEVR 229
Cdd:cd05874    17 ENIVIQCEAKGKPPPSFSWTRNGTHFD-IDKDPKVTMKPnTGTLVINIMNGEKAeayeGVYQCTARNERGAAVSNNIVIR 95

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 39.15 E-value: 2.04e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  157 VLLKCEVIGEPMPTIHWQKNQQDLNpLPGDSRVVVLpSGALQISR-LQPGDSGVYRCSARNPASIRTGNEAEVR 229
Cdd:cd04967    22 VALNCRARANPVPSYRWLMNGTEID-LESDYRYSLV-DGTLVISNpSKAKDAGHYQCLATNTVGSVLSREATLQ 93

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 39.17 E-value: 2.10e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  242 FLQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLR-GEEVI------QLRSKKYSLLGGSNLLISNVTDDDSGTYTCVVTY 314
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKeGSQNLlfpyqpPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALN 81

                          90
                  ....*....|...
gi 117168295  315 KNENISASAELTV 327
Cdd:cd05726    82 VAGSILAKAQLEV 94

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 38.34 E-value: 2.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  337 PSNLYAYESMDIEFECAVSGKPVPTVNWMKNGDVVIPSDYFQiVGGSNLRILGVVKSDEgfYQCVAENEAGNAQSSAQLI 416
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMP-VGRNVLELTNIYESAN--YTCVAISSLGMIEATAQVT 80


                  .
gi 117168295  417 V 417
Cdd:cd05739    81 V 81

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 39.24 E-value: 2.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  244 QRPSNVIAIEGKDAVLECCVSGYPP-PSFTWLRG------EEVIQLRSKKYSLLGGSN--------------LLISNVTD 302
Cdd:cd00099     3 QSPRSLSVQEGESVTLSCEVSSSFSsTYIYWYRQkpgqgpEFLIYLSSSKGKTKGGVPgrfsgsrdgtssfsLTISNLQP 82

                          90
                  ....*....|...
gi 117168295  303 DDSGTYTCVVTYK 315
Cdd:cd00099    83 EDSGTYYCAVSES 95

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 38.67 E-value: 2.33e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117168295  148 SITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPGDSRVVVLP-SGALQISRLQPGDSGVYRCSARNPA 218
Cdd:cd05894     4 TIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKdLSSFVIEGAEREDEGVYTITVTNPV 75

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 42.24 E-value: 2.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  539 TSPTSILITWEPPAYANG-PVQGYRlfctevSTGKEQNI-EVDGLSYKLEGLKKfTEYTLRFLAYNRYG---PGVSTDDI 613
Cdd:COG4733   549 TAVTTLTVSWDAPAGAVAyEVEWRR------DDGNWVSVpRTSGTSFEVPGIYA-GDYEVRVRAINALGvssAWAASSET 621

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  614 TVVTLSDVPSAPPqniSLEVVNS-RSIKVSWLPPPsgtqNGFITGYKIRHRKTTRRGEME---TLEPNNLWYLfTGLEKG 689
Cdd:COG4733   622 TVTGKTAPPPAPT---GLTATGGlGGITLSWSFPV----DADTLRTEIRYSTTGDWASATvaqALYPGNTYTL-AGLKAG 693

                         170       180       190
                  ....*....|....*....|....*....|
gi 117168295  690 SQYSFQVSAmtVNGTGPPSNWYTAETPEND 719
Cdd:COG4733   694 QTYYYRARA--VDRSGNVSAWWVSGQASAD 721

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 39.18 E-value: 2.71e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  142 FLSQTESITAFMGDTVLLKCEVIGEPMPTIHWQKNQQDLNPLPG-------DSRVVV------LPSGALQISRLQPGDSG 208
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEICSqlwdgarLDRVHInatyhqHATSTISIDNLTEEDTG 82


                  ....*...
gi 117168295  209 VYRCSARN 216
Cdd:cd20940    83 TYECRASN 90

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 38.46 E-value: 2.74e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117168295   70 PVIKWKKDGLILalgmDDRKQQLPNGS-LLIQNILHSrhhkpDEGLYQCEASLADSGSIISRTAKVTV 136
Cdd:cd05757    30 PPIQWYKDCKPL----QGDKRFIPKGSkLLIQNVTEE-----DAGNYTCKFTYTHNGKQYNVTRTISL 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.69 E-value: 3.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  243 LQRPSNVIAIEGKDAVLECCVSGYPPPSFTWLR-GEEV----IQLRSKKYSLLGGSNLLISNV----TDDDSGTYTCVV- 312
Cdd:cd07693     4 VEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKnGQPLetdkDDPRSHRIVLPSGSLFFLRVVhgrkGRSDEGVYVCVAh 83

                          90
                  ....*....|....*
gi 117168295  313 TYKNENISASAELTV 327
Cdd:cd07693    84 NSLGEAVSRNASLEV 98

IL-1 receptor-like protein; Provisional

Pssm-ID: 165173 [Multi-domain] Cd Length: 227 Bit Score: 40.67 E-value: 3.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  292 GSNLLISNVTDDDSGTYTCVVTYKNENISASAELTVlvppwflnhPSNLYAY---ESMDIEFEC--------AVSGKpvp 360
Cdd:PHA02826   97 SENLWIGNVINIDEGIYICTISSGNICEESTIRLTF---------DSGTINYqfnSGKDSKLHCygtdgissTFKDY--- 164

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 117168295  361 TVNWMKNGDVVIPSDYFQIVGG-SNLRILGVVKSDEGFYQC 400
Cdd:PHA02826  165 TLTWYKNGNIVLYTDRIQLRNNnSTLVIKSATHDDSGIYTC 205

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 38.30 E-value: 3.34e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  154 GDTVLLKCEVIGEPMPTIHWQKNQQdlnPLPGDSRV----VVLPSGALQISRLQPGDSGVYRCSARN 216
Cdd:cd05857    19 ANTVKFRCPAAGNPTPTMRWLKNGK---EFKQEHRIggykVRNQHWSLIMESVVPSDKGNYTCVVEN 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.01 E-value: 3.49e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295    41 HFVSEPSDAVTMRGGNVLLNCSAESDrGVPVIKWKKDGLilALGMDDRKQQLPNG---SLLIQNIlhsrhhKP-DEGLYQ 116
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGT-PDPEVSWFKDGQ--PLRSSDRFKVTYEGgtyTLTISNV------QPdDSGKYT 72

                           90       100
                   ....*....|....*....|
gi 117168295   117 CEASlaDSGSIISRTAKVTV 136
Cdd:pfam07679   73 CVAT--NSAGEAEASAELTV 90

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 42.06 E-value: 3.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1165 IEKPTGTDPAGRDSPIQSCQ--DLTPVSHSQSETQMGSKSASHSGQDTEDAGSSMSTLER--SLAARRATRAKLMIPMEA 1240
Cdd:pfam03154  174 LQAQSGAASPPSPPPPGTTQaaTAGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQtpTLHPQRLPSPHPPLQPMT 253

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1241 QSSNPAVVSAIPVPT-LESAQYPGILPSPTCGYPHPQFTLRPVPFP-TLSVDRGFGAGRTQSVSEGPTtQQQPMLPPAQP 1318
Cdd:pfam03154  254 QPPPPSQVSPQPLPQpSLHGQMPPMPHSLQTGPSHMQHPVPPQPFPlTPQSSQSQVPPGPSPAAPGQS-QQRIHTPPSQS 332

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  1319 EHPSSEeaPSRTiptacvrpthplrsfaNPLLPPPMSA--IEPKvPYTPLLSQPGptlPKTHVKTASLglagKARSPL-L 1395
Cdd:pfam03154  333 QLQSQQ--PPRE----------------QPLPPAPLSMphIKPP-PTTPIPQLPN---PQSHKHPPHL----SGPSPFqM 386

                          250       260
                   ....*....|....*....|....*
gi 117168295  1396 PVSVPTAPEVSEESHKPTEDPASVY 1420
Cdd:pfam03154  387 NSNLPPPPALKPLSSLSTHHPPSAH 411

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 37.81 E-value: 3.77e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   43 VSEPSDAVTMRGGNVLLNCSAEsdrGVP--VIKWKKDGLILALGMDDRKQQLPNGSLLIQNILHSrhhkpDEGLYQCEAS 120
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAE---GNPqpTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPN-----DTAVYQCNAS 74

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 38.40 E-value: 3.98e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  337 PSNLYAYESMDIEFECAVSGKPVPTVNWMK----NGDVVIPSD--YFQIV--GGSN--------LRILGVVKSDEGFYQC 400
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKhvekNGSKYGPDGlpYVEVLktAGVNttdkeievLYLRNVTFEDAGEYTC 87

                          90
                  ....*....|....*..
gi 117168295  401 VAENEAGNAQSSAQLIV 417
Cdd:cd05858    88 LAGNSIGISHHSAWLTV 104

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor-2 (IL1R2), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor-2 (IL1R2). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds the IL-1 receptor, type II (IL1R2) represented in this group. Mature IL1R2 consists of three IG-like domains, a transmembrane domain, and a short cytoplasmic domain. It lacks the large cytoplasmic domain of mature IL1R1 and does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

Pssm-ID: 409478 Cd Length: 95 Bit Score: 37.82 E-value: 4.33e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  273 WLRGEEVIQLRSKKYSLLGGS-NLLISNVTDDDSGTYTCVVTYKNE----NISASAELTVL 328
Cdd:cd05897    34 WYKDSLLLDKDNEKFLSVKGStHLLIHDVSLNDSGYYTCKLTFTHEgkkyNITRSIELRIV 94

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 37.89 E-value: 4.51e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  248 NVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKY-------SLLGGSNLLISNVTDDDSGTYTC 310
Cdd:cd05732    10 NQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLdgrivvrGHARVSSLTLKDVQLTDAGRYDC 79

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 37.19 E-value: 5.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIqlrSKKYSLLGGSNLL-ISNVTddDSGTYTCVVTYKNENISASAE 324
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEEL---TKEDEMPVGRNVLeLTNIY--ESANYTCVAISSLGMIEATAQ 78


                  ...
gi 117168295  325 LTV 327
Cdd:cd05739    79 VTV 81

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 37.37 E-value: 6.15e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117168295  155 DTVLLKCEVIGePMPTIHWQKNQQDLNP-----LPGDSRVVVLPSgalqISRlqpGDSGVYRCSARNPASIRT 222
Cdd:cd05740    16 DAVTLTCEPET-QNTSYLWWFNGQSLPVtprltLSNGNRTLTLLN----VTR---EDAGAYQCEISNPVSANR 80

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.38 E-value: 7.70e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117168295  253 EGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYS----LLGGSNLLISNVTDDDSGTYTCVVTYKNENISASAELTV 327
Cdd:cd05893    14 EGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTiqrdLDGTCSLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 37.21 E-value: 7.99e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117168295  242 FLQRPSNVIAIEG---KDAVLECCVSGYPPPSFTW-LRGEEVIQLRSKKYSLLGGsNLLISN-VTDDDSGTYTCVVT 313
Cdd:cd05850     5 FEEQPSSTLFPEGsaeEKVTLACRARASPPATYRWkMNGTELKMEPDSRYRLVAG-NLVISNpVKAKDAGSYQCLAS 80

IL-1 receptor-like protein; Provisional

Pssm-ID: 165173 [Multi-domain] Cd Length: 227 Bit Score: 39.51 E-value: 8.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  206 DSGVYRCSarnpasIRTGN---EAEVRILSDPGLHrqlyflqrpsNVIAIEGKDAVLEC-----CVSGYPPPSFTW---- 273
Cdd:PHA02826  109 DEGIYICT------ISSGNiceESTIRLTFDSGTI----------NYQFNSGKDSKLHCygtdgISSTFKDYTLTWykng 172

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117168295  274 --LRGEEVIQLRSKKysllggSNLLISNVTDDDSGTYTCVVTYK----NENISASAELTVL 328
Cdd:PHA02826  173 niVLYTDRIQLRNNN------STLVIKSATHDDSGIYTCNLRFNknsnNYNITKEYKVTII 227

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 37.21 E-value: 8.89e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295  331 PWFLNHPSNLYAYESM---DIEFECAVSGKPVPTVNWMKNGDVVI--PSDYFQIVGGsNLRILGVVKS-DEGFYQCVAEN 404
Cdd:cd05850     3 PVFEEQPSSTLFPEGSaeeKVTLACRARASPPATYRWKMNGTELKmePDSRYRLVAG-NLVISNPVKAkDAGSYQCLASN 81


                  ....*..
gi 117168295  405 EAGNAQS 411
Cdd:cd05850    82 RRGTVVS 88

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 37.19 E-value: 8.92e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117168295  352 CAVSGKPVPTVNWMKNGDVVIPSDYF--QIVGGS--NLRILGVVKSDEGFYQCVAENEAGNAQS 411
Cdd:cd05737    23 CNVWGDPPPEVSWLKNDQALAFLDHCnlKVEAGRtvYFTINGVSSEDSGKYGLVVKNKYGSETS 86

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 36.67 E-value: 9.36e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117168295  246 PSNVIAIEGKDAVLECCVSGYPPPSFTWLRGEEVIQLRSKKYSLLGGSNLLISNVTDDDSGTYTC 310
Cdd:cd04979     3 FKQISVKEGDTVILSCSVKSNNAPVTWIHNGKKVPRYRSPRLVLKTERGLLIRSAQEADAGVYEC 67

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 37.44 E-value: 9.40e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117168295   154 GDTVLLKCEV---IGEPMPTIHWQKNQQD-------------LNPLPGDSRVVVL-----PSGALQISRLQPGDSGVYRC 212
Cdd:pfam07686   11 GGSVTLPCTYsssMSEASTSVYWYRQPPGkgptfliayysngSEEGVKKGRFSGRgdpsnGDGSLTIQNLTLSDSGTYTC 90

                           90
                   ....*....|....*....
gi 117168295   213 SARNPASIRTGNEAEVRIL 231
Cdd:pfam07686   91 AVIPSGEGVFGKGTRLTVL 109