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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434   359 PRDLNISEGRMAELKCRT--PPMSSVKWLLPNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAGNSNAS 436
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsgSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 767948434   437 AYLNV 441
Cdd:smart00410  81 TTLTV 85

Leucine rich repeat N-terminal domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 767948434    46 CPSVCSCSNqfSKVVCTRRGLSEVPQGIPSNTRY 79
Cdd:smart00013   2 CPAPCNCSG--TAVDCSGRGLTEVPLDLPPDTTL 33

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434   359 PRDLNISEGRMAELKCRT--PPMSSVKWLLPNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAGNSNAS 436
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsgSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 767948434   437 AYLNV 441
Cdd:smart00410  81 TTLTV 85

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  97 HLHhlevLQlGRNsIRQIEvgAFNGLASLNTLELFDNWLTVIPSgaFEYLSKLRELWLRNNPIESIpsyafnrvpslmrl 176
Cdd:cd21340    6 HLY----LN-DKN-ITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKI-------------- 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 177 dlgelkkleyisEGaFEGLFNLKYLNLGMCNIKDMPNLTPLVGLEELEMSGNHFPE-----IRPGSFHGLS-SLKKLWVM 250
Cdd:cd21340   62 ------------EN-LENLVNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPPgekltFDPRSLAALSnSLRVLNIS 128

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767948434 251 NSQVSLIErnAFDGLASLVELNLAHNNLSSLPH--DLFTPLRYLVELHLHHNP 301
Cdd:cd21340  129 GNNIDSLE--PLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNP 179

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948434  353 PFIMDAPRDLNISEGRMAELKCRT--PPMSSVKWLLpNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTN 428
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEAtgSPPPTITWYK-NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 767948434   300 NPWNCDCDILWLAWWLR--EYIPTN-STccgRCHAPMHMRGRyLVEVDQASFQCS 351
Cdd:smart00082   1 NPFICDCELRWLLRWLQanEHLQDPvDL---RCASPSSLRGP-LLELLHSEFKCP 51

Leucine rich repeat N-terminal domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 767948434    46 CPSVCSCSNqfSKVVCTRRGLSEVPQGIPSNTRY 79
Cdd:smart00013   2 CPAPCNCSG--TAVDCSGRGLTEVPLDLPPDTTL 33

Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the N-terminus of tandem leucine rich repeats.

                          10        20
                  ....*....|....*....|....*....
gi 767948434   46 CPSVCSCSNqfSKVVCTRRGLSEVPQGIP 74
Cdd:pfam01462   2 CPVPCHCSA--TVVNCSDRGLTAVPRDLP 28

Leucine-rich repeat (LRR) protein [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  75 SNTRYLNLMENNiqmiqadTFRHLHHLEVLQLGRNSIRQIEVgAFNGLASLNTLELFDNWLTVIPSgAFEYLSKLRELWL 154
Cdd:COG4886   96 TNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLPE-PLGNLTNLKSLDL 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 155 RNNPIESIPSyafnrvpslmrldlgelkkleyisegAFEGLFNLKYLNLGMCNIKDMPN-LTPLVGLEELEMSGNHFPEI 233
Cdd:COG4886  167 SNNQLTDLPE--------------------------ELGNLTNLKELDLSNNQITDLPEpLGNLTNLEELDLSGNQLTDL 220

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948434 234 rPGSFHGLSSLKKLWVMNSQVSLIErnAFDGLASLVELNLAHNNLSSLPHDLftPLRYLVELHLHHNP 301
Cdd:COG4886  221 -PEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQ 283

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434   359 PRDLNISEGRMAELKCRT--PPMSSVKWLLPNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAGNSNAS 436
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsgSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 767948434   437 AYLNV 441
Cdd:smart00410  81 TTLTV 85

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  97 HLHhlevLQlGRNsIRQIEvgAFNGLASLNTLELFDNWLTVIPSgaFEYLSKLRELWLRNNPIESIpsyafnrvpslmrl 176
Cdd:cd21340    6 HLY----LN-DKN-ITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKI-------------- 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 177 dlgelkkleyisEGaFEGLFNLKYLNLGMCNIKDMPNLTPLVGLEELEMSGNHFPE-----IRPGSFHGLS-SLKKLWVM 250
Cdd:cd21340   62 ------------EN-LENLVNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPPgekltFDPRSLAALSnSLRVLNIS 128

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767948434 251 NSQVSLIErnAFDGLASLVELNLAHNNLSSLPH--DLFTPLRYLVELHLHHNP 301
Cdd:cd21340  129 GNNIDSLE--PLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNP 179

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 354 FIMDAPRDLNISEGRMAELKCRTP--PMSSVKWLLpNGTVLSHASRHPRiSVLNDGTLNFSHVLLSDTGVYTCMVTNVAG 431
Cdd:cd04978    1 YWIIEPPSLVLSPGETGELICEAEgnPQPTITWRL-NGVPIEPAPEDMR-RTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

                         90
                 ....*....|
gi 767948434 432 NSNASAYLNV 441
Cdd:cd04978   79 YLLANAFLHV 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 353 PFIMDAPRDLNISEGRMAELKCRT--PPMSSVKWLLPNGTVLSHASRhprISVLNDGTLNFSHVLLSDTGVYTCMVTNVA 430
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKArgDPEPAIHWISPEGKLISNSSR---TLVYDNGTLDILITTVKDTGAFTCIASNPA 77

                         90
                 ....*....|.
gi 767948434 431 GNSNASAYLNV 441
Cdd:cd05764   78 GEATARVELHI 88

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  219 GLEELEMSGNHFPEIRPGSFHGLSSLKKLWVMNSQVSLIERNAFDGLASLVELNLAHNNL 278
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  76 NTRYLNLMENNIQMIQAdtFRHLHHLEVLQLGRNSIRQIEVgaFNGLASLNTLELFDNWLTVIpSGaFEYLSKLRELWLR 155
Cdd:cd21340   25 NLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVV-EG-LENLTNLEELHIE 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 156 NNpiesipsyafnrvpslmRLDLGElkKLE-------YISEgafeglfNLKYLNLGMCNIKDMPNLTPLVGLEELEMSGN 228
Cdd:cd21340   99 NQ-----------------RLPPGE--KLTfdprslaALSN-------SLRVLNISGNNIDSLEPLAPLRNLEQLDASNN 152

                        170       180
                 ....*....|....*....|.
gi 767948434 229 HFPEIRP--GSFHGLSSLKKL 247
Cdd:cd21340  153 QISDLEEllDLLSSWPSLREL 173

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948434  353 PFIMDAPRDLNISEGRMAELKCRT--PPMSSVKWLLpNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTN 428
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEAtgSPPPTITWYK-NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  353 PFIMDAPRDLNISEGRMAELKCR---TPPMSsVKWLLpNGTVLSHASRHpriSVLNDG---TLNFSHVLLSDTGVYTCMV 426
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTvtgTPDPE-VSWFK-DGQPLRSSDRF---KVTYEGgtyTLTISNVQPDDSGKYTCVA 75

                          90
                  ....*....|....*
gi 767948434  427 TNVAGNSNASAYLNV 441
Cdd:pfam07679  76 TNSAGEAEASAELTV 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 352 APFIMDAPRDLNISEGRMAELKC--RTPPMSSVKWLLpNGTVLSHASRHPRISVLNdGTLNFSHVLLSDTGVYTCMVTNV 429
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCsaRGKPVPRITWIR-NAQPLQYAADRSTCEAGV-GELHIQDVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|..
gi 767948434 430 AGNSNASAYLNV 441
Cdd:cd20976   79 AGQVSCSAWVTV 90

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 355 IMDAPRDLNISEGRMAELKCRT--PPMSSVKWLlPNGTVLSHASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAGN 432
Cdd:cd05747    6 ILTKPRSLTVSEGESARFSCDVdgEPAPTVTWM-REGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGK 84

                 ...
gi 767948434 433 SNA 435
Cdd:cd05747   85 QEA 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 359 PRDLNISEGRMAELKCRTP---PMSSVKWLlPNGTVLshASRHPRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAG-NSN 434
Cdd:cd05724    4 PSDTQVAVGEMAVLECSPPrghPEPTVSWR-KDGQPL--NLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGeRES 80

                 ....*..
gi 767948434 435 ASAYLNV 441
Cdd:cd05724   81 RAARLSV 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 359 PRDLNISEGRMAELKCRTP--PMSSVKWLLPNGTVLSHASRHP----RISVLNDGTLNFSHVLLSDTGVYTCMVTNVAGN 432
Cdd:cd05726    6 PRDQVVALGRTVTFQCETKgnPQPAIFWQKEGSQNLLFPYQPPqpssRFSVSPTGDLTITNVQRSDVGYYICQALNVAGS 85

                         90
                 ....*....|..
gi 767948434 433 SNASAYLNVSTA 444
Cdd:cd05726   86 ILAKAQLEVTDV 97

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 359 PRDLNISEGRMAELKCRT--PPMSSVKWL-----LPNGtvlshasrhpRISVLNDGTLNFSHVLLSDTGVYTCMVTNVAG 431
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVggDPVPTVRWRkedgeLPKG----------RYEILDDHSLKIRKVTAGDMGSYTCVAENMVG 73

                         90
                 ....*....|
gi 767948434 432 NSNASAYLNV 441
Cdd:cd05725   74 KIEASATLTV 83

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434  92 ADTFRHLHHLEVLQLGRNSIRQIEVGA-FNGLA---SLNTLELFDNWLTVIPSG------AFEYLSKLRELWLRNNPIE- 160
Cdd:cd00116   16 TELLPKLLCLQVLRLEGNTLGEEAAKAlASALRpqpSLKELCLSLNETGRIPRGlqsllqGLTKGCGLQELDLSDNALGp 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 161 --SIPSYAFNRVPSLMRLDLG----ELKKLEYISEGAFEGLFNLKYLNLGMCNI-----KDMPNLTPLVG-LEELEMSGN 228
Cdd:cd00116   96 dgCGVLESLLRSSSLQELKLNnnglGDRGLRLLAKGLKDLPPALEKLVLGRNRLegascEALAKALRANRdLKELNLANN 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 229 HF-PEIRPGSFHGL---SSLKKLWVMNSQVSLIERNAFDG----LASLVELNLAHNNLSSLP----HD-LFTPLRYLVEL 295
Cdd:cd00116  176 GIgDAGIRALAEGLkanCNLEVLDLNNNGLTDEGASALAEtlasLKSLEVLNLGDNNLTDAGaaalASaLLSPNISLLTL 255

                        250
                 ....*....|
gi 767948434 296 HLhhnpWNCD 305
Cdd:cd00116  256 SL----SCND 261

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 356 MDAPRDLNISEGRMAELKCRTP--PMSSVKWLLpNGTVLSHASRHPRISVLNDgTLNFSHVLLSDTGVYTCMVTNVAGNS 433
Cdd:cd05868    3 ITAPTNLVLSPGEDGTLICRANgnPKPSISWLT-NGVPIEIAPTDPSRKVDGD-TIIFSKVQERSSAVYQCNASNEYGYL 80

                 ....*...
gi 767948434 434 NASAYLNV 441
Cdd:cd05868   81 LANAFVNV 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948434 356 MDAPRDLNISEGRMAELKCRTP--PMSSVKWLlPNGTVLShasRHPRISVLNdGTLNFSHVLLSDTGVYTCMVTNVAGNS 433
Cdd:cd05728    3 LKVISDTEADIGSSLRWECKASgnPRPAYRWL-KNGQPLA---SENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGTI 77

                 ....*...
gi 767948434 434 NASAYLNV 441
Cdd:cd05728   78 YASAELAV 85