NCBI Conserved Domain Search

Immunoglobulin (Ig)-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1) and similar proteins; member of the C2-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation (CD) 106) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen 4 (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains.

Pssm-ID: 409486 Cd Length: 101 Bit Score: 199.69 E-value: 1.56e-61

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 312 PRDPEIEMSGGLVNGSSVTVSCKVPSVYPLDRLEIELLKGETILENIEFLEDTDMKSLENKSLEMTFIPTIEDTGKALVC 391
Cdd:cd07689   1 PKDPEIEMSGPLVAGKPVTVSCSVPDVYPFDRLEIELLKGETLLESKEFLEDMDKKSLETKSLEVTFIPTIEDTGKVLVC 80

                        90       100
                ....*....|....*....|.
gi 18201909 392 QAKLHIDDMEFEPKQRQSTQT 412
Cdd:cd07689  81 RAKLHIDEMEFEPKQRQSTQE 101

Immunoglobulin (Ig)-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1) and similar proteins; member of the C2-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation (CD) 106) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen 4 (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains.

Pssm-ID: 409486 Cd Length: 101 Bit Score: 195.45 E-value: 5.95e-60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 116 PKDPEIHLSGPLEAGKPITVKCSVADVYPFDRLEIDLLKGDHLMKSQEFLEDADRKSLETKSLEVTFTPVIEDIGKVLVC 195
Cdd:cd07689   1 PKDPEIEMSGPLVAGKPVTVSCSVPDVYPFDRLEIELLKGETLLESKEFLEDMDKKSLETKSLEVTFIPTIEDTGKVLVC 80

                        90       100
                ....*....|....*....|.
gi 18201909 196 RAKLHIDEMDSVPTVRQAVKE 216
Cdd:cd07689  81 RAKLHIDEMEFEPKQRQSTQE 101

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. 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 first Ig-like domain of VCAM-1 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, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 179.79 E-value: 3.08e-54

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909  25 FKIETTPESRYLAQIGDSVSLTCSTTGCESPFFSWRTQIDSPLNGKVTNEGTTSTLTMNPVSFGNEHSYLCTATCESRKL 104
Cdd:cd20943   1 FKVEISPGSRYAAQIGDSVSLTCSTTGCESPSFSWRTQIDSPLNGKVRNEGTTSTLTLSPVSFENEHSYLCTVTCESRKL 80


                ....*....
gi 18201909 105 EKGIQVEIY 113
Cdd:cd20943  81 EKGIQVEIY 89

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: 95.22 E-value: 1.06e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 514 TAFPSESVKEGDTVIISCTCG--NVPETWIILKKKAET---GDTVLKSiDGAYTIRKAQLKDAGVYECESKNKV-GSQLR 587
Cdd:cd04979   1 TSFKQISVKEGDTVILSCSVKsnNAPVTWIHNGKKVPRyrsPRLVLKT-ERGLLIRSAQEADAGVYECHSGERVlGSTLR 79


                ....*....
gi 18201909 588 SLTLDVQGR 596
Cdd:cd04979  80 SVTLHVLER 88

Immunoglobulin C2-set domain;

Pssm-ID: 399065 Cd Length: 80 Bit Score: 81.62 E-value: 5.95e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   133 ITVKCSVaDVYPFDRLEIDLLKGdHLMKSQEFLEDADRKSLETKSLEVTFTPVIEDIGkVLVCRAKlhidemDSVPTVRQ 212
Cdd:pfam05790   1 VTVSCSN-NLLTCEVLELTLPKG-SKMDPSLKLKGQEAKSLETKKLESTFQPTTEDSG-TWVCLAS------DNDQKKLE 71


                  ....*....
gi 18201909   213 AVKELQVYI 221
Cdd:pfam05790  72 SVIEVLVLE 80

Immunoglobulin C2-set domain;

Pssm-ID: 399065 Cd Length: 80 Bit Score: 71.99 E-value: 1.40e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   329 VTVSCKVpSVYPLDRLEIELLKGeTILENIEFLEDTDMKSLENKSLEMTFIPTIEDTGkALVCQAKlhiddmEFEPKQRQ 408
Cdd:pfam05790   1 VTVSCSN-NLLTCEVLELTLPKG-SKMDPSLKLKGQEAKSLETKKLESTFQPTTEDSG-TWVCLAS------DNDQKKLE 71


                  ....*....
gi 18201909   409 STQTLYVNV 417
Cdd:pfam05790  72 SVIEVLVLE 80

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: 68.69 E-value: 2.38e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909     33 SRYLAQIGDSVSLTCSTTGCESPFFSWRTQIDSPL----NGKVTNEGTTSTLTMNPVSFGNEHSYLCTATCESRKLEKGI 108
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesgRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 18201909    109 QVEI 112
Cdd:smart00410  82 TLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 66.51 E-value: 1.54e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909    29 TTPESRYLAQIGDSVSLTCSTTGCESPFFSWRTQiDSPLN----GKVTNEGTTSTLTMNPVSFGNEHSYLCTATCESRKL 104
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKD-GQPLRssdrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEA 82


                  ....*...
gi 18201909   105 EKGIQVEI 112
Cdd:pfam07679  83 EASAELTV 90

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: 65.60 E-value: 2.42e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909    232 PSTKLQEGGSVTMTCSSEGLPAPEIFWSKKL-------DNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEV 304
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgkllaesGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 18201909    305 ELIV 308
Cdd:smart00410  82 TLTV 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: 62.21 E-value: 3.96e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   229 SVNPSTKLQEGGSVTMTCS-SEGLPAPEIFWSKKLDNGNLQHL-------SGNATLTLIAMRMEDSGIYVCEGVNLIGKN 300
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSaSTGSPGPDVTWSKEGGTLIESLKvkhdngrTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                  ....*.
gi 18201909   301 RKEVEL 306
Cdd:pfam00047  81 TLSTSL 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.66 E-value: 1.32e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909   227 VISVNPS-TKLQEGGSVTMTCSSEGLPAPEIFWSKklDNGNLQHLS--------GNATLTLIAMRMEDSGIYVCEGVN 295
Cdd:pfam13927   3 VITVSPSsVTVREGETVTLTCEATGSPPPTITWYK--NGEPISSGStrsrslsgSNSTLTISNVTRSDAGTYTCVASN 78

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: 60.21 E-value: 2.28e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909    427 SPSSILEEGSSVNMTCLSQGFPAPKILWSRQLP-------NGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKE 499
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkllaesgRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                   ....*
gi 18201909    500 VELII 504
Cdd:smart00410  81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 57.19 E-value: 2.46e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909   423 TVLVSPSS-ILEEGSSVNMTCLSQGFPAPKILWSRQ------LPNGELQPLSENATLTLISTKMEDSGVYLCEGIN 491
Cdd:pfam13927   3 VITVSPSSvTVREGETVTLTCEATGSPPPTITWYKNgepissGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 55.80 E-value: 6.22e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 242 VTMTCSSEGLPAPEIFWSK------KLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNR 301
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKngkplpPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 56.25 E-value: 6.43e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 220 YISPKNTVISVNpstklqEGGSVTMTCSSEGLPAPEIFWS---KKLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNL 296
Cdd:cd20978   3 FIQKPEKNVVVK------GGQDVTLPCQVTGVPQPKITWLhngKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNE 76

                        90
                ....*....|..
gi 18201909 297 IGKNRKEVELIV 308
Cdd:cd20978  77 IGDIYTETLLHV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.42 E-value: 5.89e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   233 STKLQEGGSVTMTCSSEGLPAPEIFWSKK------LDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVEL 306
Cdd:pfam07679   9 DVEVQEGESARFTCTVTGTPDPEVSWFKDgqplrsSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88


                  ..
gi 18201909   307 IV 308
Cdd:pfam07679  89 TV 90

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: 52.39 E-value: 1.45e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 433 EEGSSVNMTCLSQGFPAPKILWSRqlpNG-ELQPLSENA-----TLTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd20978  14 KGGQDVTLPCQVTGVPQPKITWLH---NGkPLQGPMERAtvedgTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

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: 52.01 E-value: 1.65e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 228 ISVNPSTKLQEGGSVTMTCSSEGLPApEIFWSkkLDNGNLQ-----HLS-GNATLTLIAMRMEDSGIYVCEGVNLIGKNR 301
Cdd:cd05740   4 ISSNNSNPVEDKDAVTLTCEPETQNT-SYLWW--FNGQSLPvtprlTLSnGNRTLTLLNVTREDAGAYQCEISNPVSANR 80


                ...
gi 18201909 302 KEV 304
Cdd:cd05740  81 SDP 83

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: 52.01 E-value: 1.84e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 419 PRDTTVLVspssileeGSSVNMTCLSQGFPAPKILWSR---QLPNGELQPLSENaTLTLISTKMEDSGVYLCEGINQAGR 495
Cdd:cd05725   4 PQNQVVLV--------DDSAEFQCEVGGDPVPTVRWRKedgELPKGRYEILDDH-SLKIRKVTAGDMGSYTCVAENMVGK 74


                .
gi 18201909 496 S 496
Cdd:cd05725  75 I 75

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: 51.18 E-value: 2.44e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 438 VNMTCLSQGFPAPKILWSR---QLPNGELQPLSE---NATLTLISTKMEDSGVYLCEGINQAGRSR 497
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKngkPLPPSSRDSRRSelgNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 51.76 E-value: 2.64e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFWSKKLDN--GNLQHLSGN---------ATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVEL 306
Cdd:cd05732  15 ELEQITLTCEAEGDPIPEITWRRATRGisFEEGDLDGRivvrgharvSSLTLKDVQLTDAGRYDCEASNRIGGDQQSMYL 94


                ..
gi 18201909 307 IV 308
Cdd:cd05732  95 EV 96

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: 51.34 E-value: 2.76e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 222 SPKNTVISVnpstklqeGGSVTMTCSSEGLPAPEIFWSKK--LDNGNLQHLS--GNATLTLIAMRMEDSGIYVCEGVNLI 297
Cdd:cd20952   5 GPQNQTVAV--------GGTVVLNCQATGEPVPTISWLKDgvPLLGKDERITtlENGSLQIKGAEKSDTGEYTCVALNLS 76


                ..
gi 18201909 298 GK 299
Cdd:cd20952  77 GE 78

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: 50.63 E-value: 6.08e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 435 GSSVNMTCLSQGFPAPKILW----SRQLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGR 495
Cdd:cd05856  19 GSSVRLKCVASGNPRPDITWlkdnKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 49.70 E-value: 8.41e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   423 TVLVSPSSILEEGSSVNMTCLSQGFPAPKILWSRqlpNGELQPLSENATLTLISTkmEDSGVYLCEGINQAGR-SRKEVE 501
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYK---DGSAISSSPNFFTLSVSA--EDSGTYTCVARNGRGGkVSNPVE 76


                  ...
gi 18201909   502 LII 504
Cdd:pfam13895  77 LTV 79

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: 49.98 E-value: 1.11e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFWSKKLD-----------NGNL----QHlsGNATLTLIAMRMEDSGIYVCEGVNLIGKNRK 302
Cdd:cd05870  15 ENGAATLSCKAEGEPIPEITWKRASDghtfsegdkspDGRIevkgQH--GESSLHIKDVKLSDSGRYDCEAASRIGGHQK 92


                ....
gi 18201909 303 EVEL 306
Cdd:cd05870  93 SMYL 96

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 1.34e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   419 PRDTTVLvspssileEGSSVNMTCLSQGFPAPKILWSRqlpNGelQPLSE-----------NATLTLISTKMEDSGVYLC 487
Cdd:pfam07679   7 PKDVEVQ--------EGESARFTCTVTGTPDPEVSWFK---DG--QPLRSsdrfkvtyeggTYTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 18201909   488 EGINQAGRSRKEVELII 504
Cdd:pfam07679  74 VATNSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 49.10 E-value: 1.36e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909    29 TTPESRYLAQIGDSVSLTCSTTGCESPFFSWR---TQIDSPLNGKVTNEGTTSTLTMNPVSFGNEHSYLCTAT 98
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYkngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 1.50e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 417 VAPRDTTVlvspssilEEGSSVNMTCLSQGFPAPKILWSRQLPN--GELQPLS--------ENATLTLISTKMEDSGVYL 486
Cdd:cd20954   6 VEPVDANV--------AAGQDVMLHCQADGFPTPTVTWKKATGStpGEYKDLLydpnvrilPNGTLVFGHVQKENEGHYL 77


                ....*...
gi 18201909 487 CEGINQAG 494
Cdd:cd20954  78 CEAKNGIG 85

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: 49.25 E-value: 1.89e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWSKKLDN--GNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIVQ 309
Cdd:cd05851  16 GQNVTLECFALGNPVPVIRWRKILEPmpATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

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: 48.63 E-value: 2.74e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 434 EGSSVNMTCLSQGFPAPKILW----SRQLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVELII 504
Cdd:cd05764  14 EGQRATLRCKARGDPEPAIHWispeGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 48.66 E-value: 2.77e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909    517 PSESVKEGDTVIISCTCGNVPETWIILKKKAET------GDTVLKSIDGAY-TIRKAQLKDAGVYECESKNKVGSQLRSL 589
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKllaesgRFSVSRSGSTSTlTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 18201909    590 TLDV 593
Cdd:smart00410  82 TLTV 85

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: 48.65 E-value: 2.91e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 233 STKLQEGGSVTMTCSSEGLPAPEIFWSKkldNGN----------LQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRK 302
Cdd:cd05744   9 DLEVQEGRLCRFDCKVSGLPTPDLFWQL---NGKpvrpdsahkmLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSF 85


                ....*.
gi 18201909 303 EVELIV 308
Cdd:cd05744  86 NAELVV 91

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: 47.63 E-value: 4.71e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18201909 434 EGSSVNMTCLSQGFPAPKILWSR---QLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVELII 504
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTKggsQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 47.89 E-value: 4.97e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18201909 227 VISV--NPSTK-LQEGGSVTMTCSSEGLPAPEIFWSK-----KLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVN 295
Cdd:cd20970   2 VISTpqPSFTVtAREGENATFMCRAEGSPEPEISWTRngnliIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

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: 47.98 E-value: 5.02e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 427 SPSSILEEGSSVNMTCLSQGFPAPKILWSRqlPNGELQP-----LSENATLTLISTKMEDSGVYLCEGINQAGRSR 497
Cdd:cd05876   2 SSSLVALRGQSLVLECIAEGLPTPTVKWLR--PSGPLPPdrvkyQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75

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: 47.93 E-value: 6.32e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 228 ISVNPSTK-LQEGGSVTMTCSSEGLPAPEIFWSKKLDNG-NL----QHLSGNATLTLIAM------RMEDSGIYVCEGVN 295
Cdd:cd05765   3 LVNSPTHQtVKVGETASFHCDVTGRPQPEITWEKQVPGKeNLimrpNHVRGNVVVTNIGQlviynaQPQDAGLYTCTARN 82

                        90
                ....*....|...
gi 18201909 296 LIGKNRKEVELIV 308
Cdd:cd05765  83 SGGLLRANFPLSV 95

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: 47.50 E-value: 6.99e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18201909 431 ILEEGSSVNMTCLSQGFPAPKILWSRQlpNGELQPLSEN-------ATLTLISTKMEDSGVYLCEGINQAG 494
Cdd:cd20970  13 TAREGENATFMCRAEGSPEPEISWTRN--GNLIIEFNTRyivrengTTLTIRNIRRSDMGIYLCIASNGVP 81

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: 47.64 E-value: 7.20e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 417 VAPRDTTVlvspssilEEGSSVNMTCLSQGFPAPKILWSRQ------LPNGELQP-----LSENATLTLISTKMEDSGVY 485
Cdd:cd05726   4 VKPRDQVV--------ALGRTVTFQCETKGNPQPAIFWQKEgsqnllFPYQPPQPssrfsVSPTGDLTITNVQRSDVGYY 75


                ....*....
gi 18201909 486 LCEGINQAG 494
Cdd:cd05726  76 ICQALNVAG 84

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

Pssm-ID: 409579 Cd Length: 94 Bit Score: 47.56 E-value: 7.31e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 119 PEIHLSGPLEAGKPITVKCSVADVYPFDRLEIDLLkGDHLMKSQEFLEDADRKSLETKSLEVTFTPVIEDIGKVLVCRAK 198
Cdd:cd20987   1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWL-GAALTPLPPVLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTCQVK 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: 47.00 E-value: 8.01e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 223 PKNTVISVnpstklqeGGSVTMTCSSEGLPAPEIFWSKklDNGNL----QHLSGNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd05725   4 PQNQVVLV--------DDSAEFQCEVGGDPVPTVRWRK--EDGELpkgrYEILDDHSLKIRKVTAGDMGSYTCVAENMVG 73

                        90
                ....*....|
gi 18201909 299 KNRKEVELIV 308
Cdd:cd05725  74 KIEASATLTV 83

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: 47.19 E-value: 9.42e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909   425 LVSPSSILEEGSSVNMTC-LSQGFPAPKILWSR---QLPNGELQPLSEN----ATLTLISTKMEDSGVYLCEG 489
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKeggTLIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVV 73

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: 46.86 E-value: 9.63e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFWSK-----KLDNGNLQHLSGnaTLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIV 308
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTKggsqlSVDRRHLVLSSG--TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 46.77 E-value: 1.14e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 435 GSSVNMTCLSQGFPAPKILWSRQL--PNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVELIIQ 505
Cdd:cd04968  16 GQTVTLECFALGNPVPQIKWRKVDgsPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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: 46.34 E-value: 1.73e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 417 VAPRDTTVLVspssileeGSSVNMTCLSQGFPAPKILWSRQ----LPNGELQPLSENATLTLISTKMEDSGVYLCEGINQ 492
Cdd:cd20952   4 QGPQNQTVAV--------GGTVVLNCQATGEPVPTISWLKDgvplLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL 75


                ..
gi 18201909 493 AG 494
Cdd:cd20952  76 SG 77

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: 46.39 E-value: 1.80e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWsKKLDN---GNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIVQ 309
Cdd:cd04968  16 GQTVTLECFALGNPVPQIKW-RKVDGspsSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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: 46.49 E-value: 1.87e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 227 VISVNPSTKLQEGG-SVTMTCSSEGLPAPEIFW-----------SKKLDngnlqhLSGNATLTLIA-MRMEDSGIYVCEG 293
Cdd:cd05736   2 VIRVYPEFQAKEPGvEASLRCHAEGIPLPRVQWlkngmdinpklSKQLT------LIANGSELHISnVRYEDTGAYTCIA 75

                        90
                ....*....|....*.
gi 18201909 294 VNLIGKNRKEVELIVQ 309
Cdd:cd05736  76 KNEGGVDEDISSLFVE 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: 46.30 E-value: 1.94e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 229 SVNPSTKL---QEGGSVTMTCSSEGLPAPEIFWSKK---LDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRK 302
Cdd:cd04969   4 ELNPVKKKilaAKGGDVIIECKPKASPKPTISWSKGtelLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANS 83


                ....*.
gi 18201909 303 EVELIV 308
Cdd:cd04969  84 TGSLSV 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 46.02 E-value: 1.95e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909   512 KLTAFPSES-VKEGDTVIISCTCGNVPE---TWIILKKKAETGDTVLKSIDGAY---TIRKAQLKDAGVYECESKN 580
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATGSPPptiTWYKNGEPISSGSTRSRSLSGSNstlTISNVTRSDAGTYTCVASN 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: 45.86 E-value: 2.47e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWSKK---LDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIVQ 309
Cdd:cd05731  10 GGVLLLECIAEGLPTPDIRWIKLggeLPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTVE 83

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: 46.56 E-value: 2.92e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 427 SPSSIL-EEGSSVNMTC-LSQGFPAPKILWSRQLPNGELQ------------------------PLSENATLTLISTKME 480
Cdd:cd00099   4 SPRSLSvQEGESVTLSCeVSSSFSSTYIYWYRQKPGQGPEfliylssskgktkggvpgrfsgsrDGTSSFSLTISNLQPE 83

                        90       100
                ....*....|....*....|...
gi 18201909 481 DSGVYLCeginQAGRSRKEVELI 503
Cdd:cd00099  84 DSGTYYC----AVSESGGTDKLT 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: 45.29 E-value: 3.51e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFW---SKKLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNR 301
Cdd:cd05876   9 RGQSLVLECIAEGLPTPTVKWlrpSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75

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: 45.56 E-value: 4.23e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 418 APRDTTVLvspssileEGSSVNMTCLSQGFPAPKILWSRqlpNGE-LQP-------LSENATLTLISTKM--EDSGVYLC 487
Cdd:cd05744   6 APGDLEVQ--------EGRLCRFDCKVSGLPTPDLFWQL---NGKpVRPdsahkmlVRENGRHSLIIEPVtkRDAGIYTC 74

                        90
                ....*....|....*..
gi 18201909 488 EGINQAGRSRKEVELII 504
Cdd:cd05744  75 IARNRAGENSFNAELVV 91

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: 45.01 E-value: 5.72e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 415 VNVAPRDTTVLVspssileeGSSVNMTCLSQGFPAPKILWSRQLpngELQPLS-----ENATLTLISTKMEDSGVYLCEG 489
Cdd:cd05851   4 INVKFKDTYALK--------GQNVTLECFALGNPVPVIRWRKIL---EPMPATaeismSGAVLKIFNIQPEDEGTYECEA 72

                        90
                ....*....|....*.
gi 18201909 490 INQAGRSRKEVELIIQ 505
Cdd:cd05851  73 ENIKGKDKHQARVYVQ 88

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: 44.69 E-value: 6.08e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 423 TVLVSPSSILEEGSSVNMTCLSQGfPAPKILWSRqlpNGELQPLSE-------NATLTLISTKMEDSGVYLCEGINQAGR 495
Cdd:cd05740   3 FISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWF---NGQSLPVTPrltlsngNRTLTLLNVTREDAGAYQCEISNPVSA 78


                ....*
gi 18201909 496 SRKEV 500
Cdd:cd05740  79 NRSDP 83

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: 44.71 E-value: 6.43e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 427 SPSSILE-EGSSVNMTCLSQGFPAPKILWSR---QLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd05731   1 SESSTMVlRGGVLLLECIAEGLPTPDIRWIKlggELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                ...
gi 18201909 503 IIQ 505
Cdd:cd05731  81 TVE 83

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: 44.92 E-value: 6.90e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 417 VAPRDTTVLVspssileeGSSVNMTCLSQGFPAPKILWSR----QLPNGE---LQPLSENATLTLISTKMEDSGVYLCEG 489
Cdd:cd05763   4 KTPHDITIRA--------GSTARLECAATGHPTPQIAWQKdggtDFPAARerrMHVMPEDDVFFIVDVKIEDTGVYSCTA 75


                ....*
gi 18201909 490 INQAG 494
Cdd:cd05763  76 QNSAG 80

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: 44.48 E-value: 7.54e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 435 GSSVNMTCLSQGFPAPKILW---SRQLPNGELQPLSENATLTLIS-TKMEDSGVYLCEGINQAGRS-RKEVELII 504
Cdd:cd20958  15 GQTLRLHCPVAGYPISSITWekdGRRLPLNHRQRVFPNGTLVIENvQRSSDEGEYTCTARNQQGQSaSRSVFVKV 89

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409372 [Multi-domain] Cd Length: 109 Bit Score: 44.95 E-value: 9.25e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 427 SPSSILEEGSSVNMTCLSQGFPAPKILWSRQLPNGELQPL------SENA----------------TLTLISTKMEDSGV 484
Cdd:cd04983   5 PQSLSVQEGENVTLNCNYSTSTFYYLFWYRQYPGQGPQFLiyissdSGNKkkgrfsatldksrkssSLHISAAQLSDSAV 84


                ...
gi 18201909 485 YLC 487
Cdd:cd04983  85 YFC 87

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: 44.59 E-value: 1.04e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 223 PKNTVISVNPSTKLQEggSVTMTCSSEGLPAPEIFWSKKLDN--GNLQHLSGN---------ATLTLIAMRMEDSGIYVC 291
Cdd:cd05869   3 PKITYVENQTAMELEE--QITLTCEASGDPIPSITWRTSTRNisSEEKTLDGHivvrsharvSSLTLKYIQYTDAGEYLC 80

                        90
                ....*....|....*..
gi 18201909 292 EGVNLIGKNRKEVELIV 308
Cdd:cd05869  81 TASNTIGQDSQSMYLEV 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: 43.99 E-value: 1.13e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18201909 426 VSPSSILEEGSSVNMTCLSQGFPAPKILWSR---QLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAG 494
Cdd:cd04969   8 VKKKILAAKGGDVIIECKPKASPKPTISWSKgteLLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFG 79

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: 43.72 E-value: 1.39e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 434 EGSSVNMTCLSQGFPAPKILWSRqlpngELQPLSE------------NATLTLISTKMEDSGVYLCEGINQAGRSRKEVE 501
Cdd:cd20973  11 EGSAARFDCKVEGYPDPEVKWMK-----DDNPIVEsrrfqidqdedgLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                ...
gi 18201909 502 LII 504
Cdd:cd20973  86 LTV 88

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: 44.02 E-value: 1.50e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18201909 239 GGSVTMTCSSEGLPAPEIFW--SKKLDNGNLQH---------LSGNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd05734  16 GKAVVLNCSADGYPPPTIVWkhSKGSGVPQFQHivplngriqLLSNGSLLIKHVLEEDSGYYLCKVSNDVG 86

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

Pssm-ID: 409579 Cd Length: 94 Bit Score: 43.71 E-value: 1.73e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 315 PEIEMSGGLVNGSSVTVSCKVPSVYPLDRLEIELLkGETILENIEFLEDTDMKSLENKSLEMTFIPTIEDTGKALVCQAK 394
Cdd:cd20987   1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWL-GAALTPLPPVLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTCQVK 79

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: 2.19e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909    35 YLAQIGDSVSLTCSTTGCESPF-FSWRTQIDSPLNG----KVTNEGTTSTLTMNPVSFGNEHSYLCTA 97
Cdd:pfam00047   6 VTVLEGDSATLTCSASTGSPGPdVTWSKEGGTLIESlkvkHDNGRTTQSSLLISNVTKEDAGTYTCVV 73

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: 43.17 E-value: 2.43e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 418 APRDTTVlvspssilEEGSSVNMTCLSQGFPAPKILWsrQLPNGELQPLS-------ENATLTLI--STKMEDSGVYLCE 488
Cdd:cd20990   6 APGDLTV--------QEGKLCRMDCKVSGLPTPDLSW--QLDGKPIRPDSahkmlvrENGVHSLIiePVTSRDAGIYTCI 75

                        90
                ....*....|....*.
gi 18201909 489 GINQAGRSRKEVELII 504
Cdd:cd20990  76 ATNRAGQNSFNLELVV 91

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, 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 of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 409416 Cd Length: 98 Bit Score: 43.21 E-value: 2.53e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 421 DTTVLVSPSSILEEGSSVNMTCLSQGF-PAPKILWSRqlpNGELQ--------------PLSENATLTLISTKMEDSGVY 485
Cdd:cd05759   1 DPVIEGGPVISLQAGVPYNLTCRARGAkPAAEIIWFR---DGEQLegavyskellkdgkRETTVSTLLITPSDLDTGRTF 77

                        90       100
                ....*....|....*....|.
gi 18201909 486 LCEGINQAGRSRKEVELIIQV 506
Cdd:cd05759  78 TCRARNEAIPNGKETSITLDV 98

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: 42.48 E-value: 2.84e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909 435 GSSVNMTCLSQGFPAPKILWsrQLPNG------ELQPLSENA--TLTLISTKMEDSGVYLCEGINQAGR 495
Cdd:cd05743   1 GETVEFTCVATGVPTPIINW--RLNWGhvpdsaRVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGM 67

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: 43.02 E-value: 3.01e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 218 QVYISPKNTVISvnpstklqEGGSVTMTCSSEGLPAPEIFWSKK------LDNGNLQ-----HLSGNATLTLIAMRMEDS 286
Cdd:cd05726   1 QFVVKPRDQVVA--------LGRTVTFQCETKGNPQPAIFWQKEgsqnllFPYQPPQpssrfSVSPTGDLTITNVQRSDV 72

                        90
                ....*....|..
gi 18201909 287 GIYVCEGVNLIG 298
Cdd:cd05726  73 GYYICQALNVAG 84

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 42.63 E-value: 3.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   504 IQVTPKDIKltafpsesVKEGDTVIISCTCGNVPE---TWIILKKKAETGDTVLKSIDGAY---TIRKAQLKDAGVYECE 577
Cdd:pfam07679   3 FTQKPKDVE--------VQEGESARFTCTVTGTPDpevSWFKDGQPLRSSDRFKVTYEGGTytlTISNVQPDDSGKYTCV 74

                          90
                  ....*....|....*.
gi 18201909   578 SKNKVGSQLRSLTLDV 593
Cdd:pfam07679  75 ATNSAGEAEASAELTV 90

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: 42.32 E-value: 3.47e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909  43 VSLTCSTTGCESPFFSWR---TQIDSPLNGKVTNEGTTSTLTMNPVSFGNEHSYLCTAT 98
Cdd:cd00096   1 VTLTCSASGNPPPTITWYkngKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

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: 43.22 E-value: 3.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   230 VNPSTKLQEGGSVTMTC---SSEGLPAPEIFWSKKLDNGNLQHL------------------------SGNATLTLIAMR 282
Cdd:pfam07686   2 TPREVTVALGGSVTLPCtysSSMSEASTSVYWYRQPPGKGPTFLiayysngseegvkkgrfsgrgdpsNGDGSLTIQNLT 81

                          90       100
                  ....*....|....*....|....*..
gi 18201909   283 MEDSGIYVCEGV-NLIGKNRKEVELIV 308
Cdd:pfam07686  82 LSDSGTYTCAVIpSGEGVFGKGTRLTV 108

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: 42.78 E-value: 4.19e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 236 LQEGGSVTMTCSSEGLPAPEIFWS-----KKLDNGNLQHLSGNATLTLI--AMRMEDSGIYVCEGVNLIGKNRKEVELIV 308
Cdd:cd20990  12 VQEGKLCRMDCKVSGLPTPDLSWQldgkpIRPDSAHKMLVRENGVHSLIiePVTSRDAGIYTCIATNRAGQNSFNLELVV 91

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409372 [Multi-domain] Cd Length: 109 Bit Score: 43.03 E-value: 4.78e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 227 VISVNPSTKLQEGGSVTMTCSSEGLPAPEIFWSKKLDNGNLQHL------SGNA----------------TLTLIAMRME 284
Cdd:cd04983   1 VTQSPQSLSVQEGENVTLNCNYSTSTFYYLFWYRQYPGQGPQFLiyissdSGNKkkgrfsatldksrkssSLHISAAQLS 80


                ....*..
gi 18201909 285 DSGIYVC 291
Cdd:cd04983  81 DSAVYFC 87

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: 42.18 E-value: 4.91e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFWSKkldNGN----------LQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELI 307
Cdd:cd20973  11 EGSAARFDCKVEGYPDPEVKWMK---DDNpivesrrfqiDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                .
gi 18201909 308 V 308
Cdd:cd20973  88 V 88

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 45.78 E-value: 5.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909  429 SSILE-EGSSVNMTC-----LSQGFPAPKILWS-RQLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVE 501
Cdd:PHA02785  34 ASFMElENEPVILPCpqintLSSGYNILDILWEkRGADNDRIIPIDNGSNMLILNPTQSDSGIYICITKNETYCDMMSLN 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909  502 L-IIQVTPKDIKLTAFPsESVKEGDTVIISC------TCGNVPETWIILKKKAETGDTVLKSIDGAYTIRKAQLKDAGVY 574
Cdd:PHA02785 114 LtIVSVSESNIDLISYP-QIVNERSTGEMVCpninafIASNVNADIIWSGHRRLRNKRLKQRTPGIITIEDVRKNDAGYY 192

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 18201909  575 ECESKNKVGSQLRSLT----LDVQGRENNKDYFSPELLVLYFASSLII 618
Cdd:PHA02785 193 TCVLKYIYGDKTYNVTrivkLEVRDRIIPPTMQLPEGVVTSIGSNLTI 240

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: 42.34 E-value: 5.68e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 423 TVLVSPSSI-LEEGSSVNMTCLSQGFPAPKILWSRqlpngELQPLSENATLTLISTK-----------MEDSGVYLCEGI 490
Cdd:cd05747   5 TILTKPRSLtVSEGESARFSCDVDGEPAPTVTWMR-----EGQIIVSSQRHQITSTEykstfeiskvqMSDEGNYTVVVE 79

                        90
                ....*....|..
gi 18201909 491 NQAGRSRKEVEL 502
Cdd:cd05747  80 NSEGKQEAQFTL 91

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: 41.75 E-value: 7.19e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 413 LYVNVAPRDTTVLVspssileeGSSVNMTCLSQGFPAPKILW---SRQLPNGELQPLSENATLTLISTKMEDSGVYLCEG 489
Cdd:cd20957   2 LSATIDPPVQTVDF--------GRTAVFNCSVTGNPIHTVLWmkdGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFV 73

                        90
                ....*....|...
gi 18201909 490 INQAGRSRKEVEL 502
Cdd:cd20957  74 RNDGDSAQATAEL 86

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: 42.15 E-value: 7.60e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 423 TVLVSPS-SILEEGSSVNMTCLSQGFPAPKILWSRQLPNGELQPLSEN-----------ATLTLISTKMEDSGVYLCEGI 490
Cdd:cd05765   2 ALVNSPThQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNhvrgnvvvtniGQLVIYNAQPQDAGLYTCTAR 81


                ....
gi 18201909 491 NQAG 494
Cdd:cd05765  82 NSGG 85

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: 41.69 E-value: 8.66e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFW----SKKLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIV 308
Cdd:cd05764  14 EGQRATLRCKARGDPEPAIHWispeGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 41.32 E-value: 9.47e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWskKLDNGNL--------QHLSGNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd05743   1 GETVEFTCVATGVPTPIINW--RLNWGHVpdsarvsiTSEGGYGTLTIRDVKESDQGAYTCEAINTRG 66

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: 41.74 E-value: 1.01e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 434 EGSSVNMTCLSQGFPAPKILWSR---------QLPNGELQPLSEN--ATLTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd05732  15 ELEQITLTCEAEGDPIPEITWRRatrgisfeeGDLDGRIVVRGHArvSSLTLKDVQLTDAGRYDCEASNRIGGDQQSMYL 94


                ..
gi 18201909 503 II 504
Cdd:cd05732  95 EV 96

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: 41.50 E-value: 1.26e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 434 EGSSVNMTCLSQGFPAPKILWSR-----------QLPNG--ELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEV 500
Cdd:cd05870  15 ENGAATLSCKAEGEPIPEITWKRasdghtfsegdKSPDGriEVKGQHGESSLHIKDVKLSDSGRYDCEAASRIGGHQKSM 94


                ....
gi 18201909 501 ELII 504
Cdd:cd05870  95 YLDI 98

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: 40.94 E-value: 1.31e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18201909  40 GDSVSLTCSTTGCESPFFSWRTQ---IDSPLNGKVTNEGTTSTLTMNPVSFGNEHSYLCTA 97
Cdd:cd05743   1 GETVEFTCVATGVPTPIINWRLNwghVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEA 61

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: 41.09 E-value: 1.70e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 424 VLVSPSSILEE-GSSVNMTCLSQGFPAPKILWsrqLPNGELQPLSENATLTLI---------STKMEDSGVYLCEGINQA 493
Cdd:cd05736   3 IRVYPEFQAKEpGVEASLRCHAEGIPLPRVQW---LKNGMDINPKLSKQLTLIangselhisNVRYEDTGAYTCIAKNEG 79

                        90
                ....*....|..
gi 18201909 494 GRSRKEVELIIQ 505
Cdd:cd05736  80 GVDEDISSLFVE 91

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409480 Cd Length: 110 Bit Score: 41.11 E-value: 1.81e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 427 SPSS-ILEEGSSVNMTClSQGFPAPKILWSRQLPNGELQ-------------------------PLSENATLTLISTKME 480
Cdd:cd05899   4 SPRYlIKRRGQSVTLRC-SQKSGHDNMYWYRQDPGKGLQllfysyggglneegdlpgdrfsasrPSLTRSSLTIKSAEPE 82


                ....*..
gi 18201909 481 DSGVYLC 487
Cdd:cd05899  83 DSAVYLC 89

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: 40.61 E-value: 2.07e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 239 GGSVTMTCSSEGLPAPEIFW---SKKLDNGNLQHLSGNA-TLTLIAMRMEDSGIYVCEGVNLIGK 299
Cdd:cd05856  19 GSSVRLKCVASGNPRPDITWlkdNKPLTPPEIGENKKKKwTLSLKNLKPEDSGKYTCHVSNRAGE 83

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: 40.69 E-value: 2.19e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 435 GSSVNMTCLSQGFPAPKILWSRQ---LPNGELQ-PLSENAT-LTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd05730  18 GQSVTLACDADGFPEPTMTWTKDgepIESGEEKySFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHL 90

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. 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 first Ig-like domain of VCAM-1 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, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 40.34 E-value: 2.48e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18201909 228 ISVNPSTKLQEGGSVTMTCSSEGLPAPEIFWSKKLD---NGNLQHLSGNATLTLIAMRMEDSGIYVC 291
Cdd:cd20943   5 ISPGSRYAAQIGDSVSLTCSTTGCESPSFSWRTQIDsplNGKVRNEGTTSTLTLSPVSFENEHSYLC 71

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: 40.69 E-value: 2.51e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 228 ISVNPSTKLqeGGSVTMTCSSEGLPAPEIFWSKK---LDNGNLQHL--SGNATLTLIAMRMEDSGIYVCEGVNLIGKNRK 302
Cdd:cd05730   9 SEVNATANL--GQSVTLACDADGFPEPTMTWTKDgepIESGEEKYSfnEDGSEMTILDVDKLDEAEYTCIAENKAGEQEA 86


                ....*...
gi 18201909 303 EVELIVQA 310
Cdd:cd05730  87 EIHLKVFA 94

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: 40.08 E-value: 3.06e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 235 KLQEGGSVTMTCSSEGLPAPEIFW-------SKKLDNGNLQH-LSGNATLTLIAMRMEDSGIYVCEGVNLIGK 299
Cdd:cd05893  11 KIFEGMPVTFTCRVAGNPKPKIYWfkdgkqiSPKSDHYTIQRdLDGTCSLHTTASTLDDDGNYTIMAANPQGR 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: 40.26 E-value: 3.10e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 233 STKLQEGGSVTMTCSSEGLPAPEIFW---SKKLDNG-NLQHLSGNATLTLIAMRM--EDSGIYVCEGVNLIGKNRKEVEL 306
Cdd:cd20972  10 SQEVAEGSKVRLECRVTGNPTPVVRWfceGKELQNSpDIQIHQEGDLHSLIIAEAfeEDTGRYSCLATNSVGSDTTSAEI 89


                ..
gi 18201909 307 IV 308
Cdd:cd20972  90 FV 91

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: 39.87 E-value: 3.85e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 429 SSILEEGSSVNMTCLSQGFPAPKILWSR---QLPNG-ELQPLSENATLTLISTKM--EDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd20972  10 SQEVAEGSKVRLECRVTGNPTPVVRWFCegkELQNSpDIQIHQEGDLHSLIIAEAfeEDTGRYSCLATNSVGSDTTSAEI 89


                ..
gi 18201909 503 II 504
Cdd:cd20972  90 FV 91

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 39.46 E-value: 4.14e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 423 TVLVSPSSILE--EGSSVNMTCLSQG-FPAPKILWSRQlpNGEL--QPLSENATLTLISTKMEDSGVYLCEGINQ 492
Cdd:cd05754   2 QVTVEEPRSQEvrPGADVSFICRAKSkSPAYTLVWTRV--NGTLpsRAMDFNGILTIRNVQLSDAGTYVCTGSNM 74

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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: 409545 Cd Length: 95 Bit Score: 39.83 E-value: 4.17e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 418 APRDTTVLVSPSSILEEGSSVNMTCLSQGFPAPKILW-------SRQLP---NGELQPLSenATLTLISTKMEDSGVYLC 487
Cdd:cd20953   1 APKIPGLSKSQPLTVSSASSIALLCPAQGYPAPSFRWykfiegtTRKQAvvlNDRVKQVS--GTLIIKDAVVEDSGKYLC 78

                        90
                ....*....|....*....
gi 18201909 488 EGINQAGrsRKEVELIIQV 506
Cdd:cd20953  79 VVNNSVG--GESVETVLTV 95

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: 39.78 E-value: 4.18e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18201909 435 GSSVNMTCLSQGFPAPKILWSRQ------------LPNGELQPLSeNATLTLISTKMEDSGVYLCEGINQAG 494
Cdd:cd05734  16 GKAVVLNCSADGYPPPTIVWKHSkgsgvpqfqhivPLNGRIQLLS-NGSLLIKHVLEEDSGYYLCKVSNDVG 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 4.21e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   225 NTVISVNPSTkLQEGGSVTMTCSSEGLPAPEIFWSKkldNGNlqHLSGNATLTLIAMRMEDSGIYVCEGVN-LIGKNRKE 303
Cdd:pfam13895   1 KPVLTPSPTV-VTEGEPVTLTCSAPGNPPPSYTWYK---DGS--AISSSPNFFTLSVSAEDSGTYTCVARNgRGGKVSNP 74


                  ....*
gi 18201909   304 VELIV 308
Cdd:pfam13895  75 VELTV 79

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: 39.82 E-value: 4.32e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 512 KLTAFPSESVKEGDTVIISCTCGN--VPE-TW------IILKKKAETGDTVLKSIDG--AYTIRKAQLKDAGVYECESKN 580
Cdd:cd05732   4 KITYLENQTAVELEQITLTCEAEGdpIPEiTWrratrgISFEEGDLDGRIVVRGHARvsSLTLKDVQLTDAGRYDCEASN 83

                        90
                ....*....|...
gi 18201909 581 KVGSQLRSLTLDV 593
Cdd:cd05732  84 RIGGDQQSMYLEV 96

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: 39.69 E-value: 4.47e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 230 VNPS-TKLQEGGSVTMTCSS-EGLPAPEIFWSKK-------------LDNGNLqhlsgnatltLIA-MRMEDSGIYVCEG 293
Cdd:cd05724   2 VEPSdTQVAVGEMAVLECSPpRGHPEPTVSWRKDgqplnldnervriVDDGNL----------LIAeARKSDEGTYKCVA 71

                        90
                ....*....|....*.
gi 18201909 294 VNLIGKNRKEV-ELIV 308
Cdd:cd05724  72 TNMVGERESRAaRLSV 87

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: 39.49 E-value: 4.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   517 PSESVKEGDTVIISCTC-GNVPETWIILKKKAETGDTVLKSIDGAY-------TIRKAQLKDAGVYECESKNKVGSQLRS 588
Cdd:pfam00047   4 PTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqsslLISNVTKEDAGTYTCVVNNPGGSATLS 83


                  ...
gi 18201909   589 LTL 591
Cdd:pfam00047  84 TSL 86

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. 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 first Ig-like domain of VCAM-1 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, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 39.57 E-value: 4.83e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 423 TVLVSPSS--ILEEGSSVNMTCLSQGFPAPKILWSRQLP---NGELQPLSENATLTLISTKMEDSGVYLCEGINQagrsR 497
Cdd:cd20943   2 KVEISPGSryAAQIGDSVSLTCSTTGCESPSFSWRTQIDsplNGKVRNEGTTSTLTLSPVSFENEHSYLCTVTCE----S 77


                ....*....
gi 18201909 498 KEVELIIQV 506
Cdd:cd20943  78 RKLEKGIQV 86

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: 39.53 E-value: 5.08e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWSKklDNGN---------LQHLSGNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd05763  14 GSTARLECAATGHPTPQIAWQK--DGGTdfpaarerrMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

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: 38.70 E-value: 5.22e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909 242 VTMTCSSEGLPAPEIFWSKK----LDNGNLqHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVEL 306
Cdd:cd05746   1 VQIPCSAQGDPEPTITWNKDgvqvTESGKF-HISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 39.30 E-value: 5.56e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFW-------SKKLDNGNLQHLSGnATLTLIAMRMEDSGIYVCEGVNLIGKNRKEVELIV 308
Cdd:cd20969  16 EGHTVQFVCRADGDPPPAILWlsprkhlVSAKSNGRLTVFPD-GTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 39.02 E-value: 5.73e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 232 PSTKLQEGGSVTMTCSSEGLPAPEIFWSKKLDNGNLQHlsgnaTLTLIAMRMEDSGIYVCEGVN-LIGKNRKEVELIV 308
Cdd:cd20948   3 SDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQ-----ELFLPAITENNEGTYTCSAHNsLTGKNISLVLSVT 75

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: 39.57 E-value: 5.80e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 506 VTPKDIKLTafpSESVKEGDTVIISCTCGN--VPE-TWiilkKKAETGDTVL---KSIDG-----------AYTIRKAQL 568
Cdd:cd05870   1 VQPHIIQLK---NETTVENGAATLSCKAEGepIPEiTW----KRASDGHTFSegdKSPDGrievkgqhgesSLHIKDVKL 73

                        90       100
                ....*....|....*....|....*
gi 18201909 569 KDAGVYECESKNKVGSQLRSLTLDV 593
Cdd:cd05870  74 SDSGRYDCEAASRIGGHQKSMYLDI 98

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: 39.30 E-value: 6.38e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 433 EEGSSVNMTCLSQGFPAPKILWSRqlPNGELQPLSENATLTLIS--------TKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd20969  15 DEGHTVQFVCRADGDPPPAILWLS--PRKHLVSAKSNGRLTVFPdgtlevryAQVQDNGTYLCIAANAGGNDSMPAHL 90

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: 39.16 E-value: 6.64e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 227 VISVNPSTKLQEGGSVTMTCSSEGLPAPEIFWSK-----KLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKNR 301
Cdd:cd20976   4 FSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRnaqplQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVS 83


                ....*..
gi 18201909 302 KEVELIV 308
Cdd:cd20976  84 CSAWVTV 90

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: 38.97 E-value: 7.61e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 428 PSSILEEGSSVNMTCLSQGFPAPKILWSRqlpNGE-LQPLSENATL-----TLISTKME--DSGVYLCEGINQAG 494
Cdd:cd04978   7 PSLVLSPGETGELICEAEGNPQPTITWRL---NGVpIEPAPEDMRRtvdgrTLIFSNLQpnDTAVYQCNASNVHG 78

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 39.33 E-value: 7.78e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 223 PKNTVISVNPSTkLQEGGSVTMTC-SSEGLPAPEIFW----------SKKLDNGNLQHLSGNATLTLIAMRMEDSGIYVC 291
Cdd:cd05761   4 PEKPVITGFTSP-VVEGDEITLTCtTSGSKPAADIRWfkndkelkgvKEVQESGAGKTFTVTSTLRFRVDRDDDGVAVIC 82


                .
gi 18201909 292 E 292
Cdd:cd05761  83 R 83

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: 39.08 E-value: 8.13e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 428 PSSILEEGSSVNMTCLSQGFPAPKILWSRqlpNGelQPLSENATLTL---------------IS-TKMEDSGVYLCEGIN 491
Cdd:cd20956   9 SEQTLQPGPSVSLKCVASGNPLPQITWTL---DG--FPIPESPRFRVgdyvtsdgdvvsyvnISsVRVEDGGEYTCTATN 83


                ...
gi 18201909 492 QAG 494
Cdd:cd20956  84 DVG 86

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: 38.61 E-value: 9.52e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 432 LEEGSSVNMTCLSQGFPAPKILW--SRQLPNGELQPLSENAT-----LTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd20975  12 VREGQDVIMSIRVQGEPKPVVSWlrNRQPVRPDQRRFAEEAEgglcrLRILAAERGDAGFYTCKAVNEYGARQCEARL 89

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 38.69 E-value: 9.60e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 228 ISVNP--STKLQEGGSVTMTCSSEG-LPAPEIFWSKklDNGNL--QHLSGNATLTLIAMRMEDSGIYVCEGVN 295
Cdd:cd05754   3 VTVEEprSQEVRPGADVSFICRAKSkSPAYTLVWTR--VNGTLpsRAMDFNGILTIRNVQLSDAGTYVCTGSN 73

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: 38.35 E-value: 9.98e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 435 GSSVNMTCLSQGFPAPKILWsrqLPNGelQPLS-------ENATLTLISTKMEDSGVYLCEGINQAGRSRKEVEL 502
Cdd:cd05728  14 GSSLRWECKASGNPRPAYRW---LKNG--QPLAsenrievEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAEL 83

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: 38.98 E-value: 1.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909   426 VSPSSIL-EEGSSVNMTC---LSQGFPAPKILWSRQLPNGELQ------------------------PLSENATLTLIST 477
Cdd:pfam07686   1 QTPREVTvALGGSVTLPCtysSSMSEASTSVYWYRQPPGKGPTfliayysngseegvkkgrfsgrgdPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
gi 18201909   478 KMEDSGVYLCEGI-NQAGRSRKEVELII 504
Cdd:pfam07686  81 TLSDSGTYTCAVIpSGEGVFGKGTRLTV 108

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: 38.42 E-value: 1.25e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909  29 TTPESRYLAQIGDSVSLTCSTTGCESPFFSWRTQI------DSPLNGK--VTNEGTTSTLTMNPVSFGNEHSYLCTAT 98
Cdd:cd05869   6 TYVENQTAMELEEQITLTCEASGDPIPSITWRTSTrnisseEKTLDGHivVRSHARVSSLTLKYIQYTDAGEYLCTAS 83

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: 38.28 E-value: 1.34e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 217 LQVYISPKNTVISVnpstklqeGGSVTMTCSSEGLPAPEIFW---SKKLDNGNLQHLSGNATLTLIAMRMEDSGIYVC 291
Cdd:cd20957   2 LSATIDPPVQTVDF--------GRTAVFNCSVTGNPIHTVLWmkdGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQC 71

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: 38.31 E-value: 1.42e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18201909 236 LQEGGSVTMTCSSEGLPAPEIFWSkkLDNGNL---------QHLSGNATLT----LIAMRMEDSGIYVCEGVNLIGK 299
Cdd:cd20956  13 LQPGPSVSLKCVASGNPLPQITWT--LDGFPIpesprfrvgDYVTSDGDVVsyvnISSVRVEDGGEYTCTATNDVGS 87

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: 38.30 E-value: 1.53e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18201909 519 ESVKEGDTVIISCTCGNVPE---TW---------IILKKKAETGDTVLKSIdGAYTIRKAQLKDAGVYECESKNKVGS 584
Cdd:cd05765  10 QTVKVGETASFHCDVTGRPQpeiTWekqvpgkenLIMRPNHVRGNVVVTNI-GQLVIYNAQPQDAGLYTCTARNSGGL 86

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: 37.95 E-value: 1.72e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18201909 239 GGSVTMTCSSEGLPAPEIFWS------KKLDNGNLQHLSGNAtLTLIAMRMEDSGIYVCEGVN 295
Cdd:cd05867  14 GETARLDCQVEGIPTPNITWSingapiEGTDPDPRRHVSSGA-LILTDVQPSDTAVYQCEARN 75

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: 37.83 E-value: 1.91e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 233 STKLQEGGSVTMTCSSEGLPAPEIFWSKklDNGNLQHL----------SGNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd05892   9 NKKVLEGDPVRLECQISAIPPPQIFWKK--NNEMLQYNtdrislyqdnCGRICLLIQNANKKDAGWYTVSAVNEAG 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: 37.67 E-value: 2.23e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18201909 238 EGGSVTMTCSSEGLPAPEIFWSKK---LDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGK 299
Cdd:cd05852  16 KGGRVIIECKPKAAPKPKFSWSKGtelLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGK 80

T-cell surface glycoprotein CD3 delta chain; This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex.

Pssm-ID: 465231 Cd Length: 63 Bit Score: 36.46 E-value: 2.67e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 18201909   239 GGSVTMTCSSEGlpaPEIFWskkLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEG 293
Cdd:pfam16680   1 DGKVLLTCNSSS---KSITW---LKDGKGIKSTNTKTLDLGKFSEDPRGLYQCQG 49

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: 37.29 E-value: 3.25e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18201909 234 TKLQEGGSVTMTCSSEGLPAPEIFWSKK-----------LDNGNLQHLSgNATLTLIAMRMEDSGIYVCEGVNLIG 298
Cdd:cd20954  11 ANVAAGQDVMLHCQADGFPTPTVTWKKAtgstpgeykdlLYDPNVRILP-NGTLVFGHVQKENEGHYLCEAKNGIG 85

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: 37.10 E-value: 3.96e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909 521 VKEGDTVIISCTCGNVPE---TWIILKKKAETGDT--VLKSIDGAYTIRKAQLKDAGVYECESKNKV-GSQLRSLTLDV 593
Cdd:cd20970  14 AREGENATFMCRAEGSPEpeiSWTRNGNLIIEFNTryIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRITLQV 92

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

Pssm-ID: 409445 Cd Length: 101 Bit Score: 36.77 E-value: 5.02e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909 445 QGFPAPKILWsrqLPNGelQPLSENAT-----------------LTLISTKMEDSGVYLCEGINQAGRSRKEVELIIQV 506
Cdd:cd05859  28 EAYPPPQIRW---LKDN--RTLIENLTeittstrnvqetryvskLKLIRAKEEDSGLYTALAQNEDAVKSYTFALQIQV 101

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: 36.63 E-value: 5.78e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18201909 433 EEGSSVNMTCLSQGFPAPKILWSRqlpNGE-LQPLSENA-----------TLTLISTKMEDSGVYLCEGINQAG 494
Cdd:cd20951  13 WEKSDAKLRVEVQGKPDPEVKWYK---NGVpIDPSSIPGkykieseygvhVLHIRRVTVEDSAVYSAVAKNIHG 83

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

Pssm-ID: 409381 Cd Length: 100 Bit Score: 36.61 E-value: 7.28e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 237 QEGGSVTMTCS-SEGLPAPEIFWSKKLDNG------------------NLQHLSGNATLTLIAMRMEDSGIYVCeGVNLI 297
Cdd:cd05716  10 VEGGSVTIQCPyPPKYASSRKYWCKWGSEGcqtlvssegvvpggrislTDDPDNGVFTVTLNQLRKEDAGWYWC-GVGDD 88

                        90
                ....*....|..
gi 18201909 298 GKNRKEVELIVQ 309
Cdd:cd05716  89 GDRGLTVQVKLV 100

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: 35.83 E-value: 8.66e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18201909  26 KIETTPESRYLAQIGDSVSLTCSTTGCESPFFSW----RTQIDSPLNGKVTNegttSTLTMNPVSFGNEHSYLCTATCE 100
Cdd:cd20978   2 KFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWlhngKPLQGPMERATVED----GTLTIINVQPEDTGYYGCVATNE 76

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: 36.37 E-value: 8.79e-03

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                ....*....|....*....|....*....|....*..
gi 18201909 559 GAYTIRKAQLKDAGVYECESKNKVGSQLRSLTLDVQG 595
Cdd:cd04970  64 GDLEIVNAQLKHAGRYTCTAQTVVDSDSASATLVVRG 100

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) delta chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the delta chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409503 Cd Length: 112 Bit Score: 36.34 E-value: 9.28e-03

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18201909 227 VISVNPSTKLQEGGSVTMTCSSE-GLPAPEIFWSKKLDNGNLQHL------SGNAT----------------LTLIAMRM 283
Cdd:cd07706   2 VTQAQPDVSVQVGEEVTLNCRYEtSWTNYYLFWYKQLPSGEMTFLirqdssEQNAKsgrysvnfqkaqksisLTISALQL 81


                ....*...
gi 18201909 284 EDSGIYVC 291
Cdd:cd07706  82 EDSAKYFC 89