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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1320 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1397
Cdd:cd20978      4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                           90
                   ....*....|...
gi 1034591376 1398 NALGKAVATSVLH 1410
Cdd:cd20978     75 NEIGDIYTETLLH 87

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034591376  449 WEHNPWTACSVSCGGGIQRRSFVCVEEsmHGEILQVEEWkCMYAPKPKVMQTCNLFDC 506
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQK--GGGSIVPDSE-CSAQKKPPETQSCNLKPC 55

ADAMTS cysteine-rich domain; This cysteine rich domain is found in a variety of ADAMTS and ADAMTS-like endopeptidases widely spread in animals. It is a well-conserved cysteine-rich sequence containing 10 cysteine residues. ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase, pfam08516) and consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organization. Members of the ADAMTS family have been implicated in a range of diseases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376  129 DFRAQQCSAYNDVQYQ-----GHYYEW---LPrYNDPAAPCALKCHAQGQNLVVELAPKVLDGTRC------NTDSLDMC 194
Cdd:pfam19236    4 EFMSQQCARTDGQPLRsspggASFYHWgaaVP-HSQGDALCRHMCRAIGESFIMKRGDSFLDGTRCmpsgprEDGTLSLC 82

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1034591376  195 ISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTC 227
Cdd:pfam19236   83 VLGSCRTFGCDGRMDSQQVWDRCQVCGGDNSTC 115

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034591376  956 SVIIKCPVRRFQKSLIQWEKDGRCLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIA----GSAQETVVL 1020
Cdd:cd04969     19 DVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAvnffGKANSTGSL 87

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376  675 WEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMsQACNTEPC 730
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQKKPPET-QSCNLKPC 55

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034591376 1455 WEPGNWSHCSATCGHlGARIQRPQCVMANGQE-VSEALCDHLQKPLAgFEPCNIRDC 1510
Cdd:pfam19030    1 WVAGPWGECSVTCGG-GVQTRLVQCVQKGGGSiVPDSECSAQKKPPE-TQSCNLKPC 55

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376  852 VGDWSKCSVSCGVGIQRRKQVCQRlaaKGRRIPLSEMMCRDLPGLPLVRSCQMPEC 907
Cdd:pfam19030    3 AGPWGECSVTCGGGVQTRLVQCVQ---KGGGSIVPDSECSAQKKPPETQSCNLKPC 55

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376  597 PEPWSACSTTCGPGVQVREVKCRVLLTFTQTETELPEEEcegPKLPTERPCLLEAC 652
Cdd:pfam19030    3 AGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQ---KKPPETQSCNLKPC 55

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1320 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1397
Cdd:cd20978      4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                           90
                   ....*....|...
gi 1034591376 1398 NALGKAVATSVLH 1410
Cdd:cd20978     75 NEIGDIYTETLLH 87

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1336 VEAALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNG---SLLLQNVSLENEGTYVCIATNALGKAVATSVLH 1410
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrsSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034591376  449 WEHNPWTACSVSCGGGIQRRSFVCVEEsmHGEILQVEEWkCMYAPKPKVMQTCNLFDC 506
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQK--GGGSIVPDSE-CSAQKKPPETQSCNLKPC 55

ADAMTS cysteine-rich domain; This cysteine rich domain is found in a variety of ADAMTS and ADAMTS-like endopeptidases widely spread in animals. It is a well-conserved cysteine-rich sequence containing 10 cysteine residues. ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase, pfam08516) and consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organization. Members of the ADAMTS family have been implicated in a range of diseases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376  129 DFRAQQCSAYNDVQYQ-----GHYYEW---LPrYNDPAAPCALKCHAQGQNLVVELAPKVLDGTRC------NTDSLDMC 194
Cdd:pfam19236    4 EFMSQQCARTDGQPLRsspggASFYHWgaaVP-HSQGDALCRHMCRAIGESFIMKRGDSFLDGTRCmpsgprEDGTLSLC 82

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1034591376  195 ISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTC 227
Cdd:pfam19236   83 VLGSCRTFGCDGRMDSQQVWDRCQVCGGDNSTC 115

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034591376  956 SVIIKCPVRRFQKSLIQWEKDGRCLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIA----GSAQETVVL 1020
Cdd:cd04969     19 DVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAvnffGKANSTGSL 87

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376  675 WEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMsQACNTEPC 730
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQKKPPET-QSCNLKPC 55

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034591376 1455 WEPGNWSHCSATCGHlGARIQRPQCVMANGQE-VSEALCDHLQKPLAgFEPCNIRDC 1510
Cdd:pfam19030    1 WVAGPWGECSVTCGG-GVQTRLVQCVQKGGGSiVPDSECSAQKKPPE-TQSCNLKPC 55

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376  852 VGDWSKCSVSCGVGIQRRKQVCQRlaaKGRRIPLSEMMCRDLPGLPLVRSCQMPEC 907
Cdd:pfam19030    3 AGPWGECSVTCGGGVQTRLVQCVQ---KGGGSIVPDSECSAQKKPPETQSCNLKPC 55

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1212 PPSIS-FNKTINSRIGNTVYITkrtevinilCDLITPSEATYTWTKDGTLLQP---SVKIILDGTGKIQIQNPTRKEQGI 1287
Cdd:pfam13927    1 KPVITvSPSSVTVREGETVTLT---------CEATGSPPPTITWYKNGEPISSgstRSRSLSGSNSTLTISNVTRSDAGT 71

                   ....*..
gi 1034591376 1288 YECSVAN 1294
Cdd:pfam13927   72 YTCVASN 78

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1034591376   734 WHVGSWGPCSATCGVGIQTRDVYCLHPGEtPAPPEECRDEKPHAlQACNQFDCP 787
Cdd:smart00209    2 SEWSEWSPCSVTCGGGVQTRTRSCCSPPP-QNGGGPCTGEDVET-RACNEQPCP 53

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376  370 WRQTDFFPCTVTCGGGYQLNSAECVDIRLKRVVPDHYChyypeNVKPKPKLKE-CSMDPC 428
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSEC-----SAQKKPPETQsCNLKPC 55

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034591376   853 GDWSKCSVSCGVGIQRRKQVCQRlaakgrriPLSEMMCRDLPGLPL-VRSCQMPECS 908
Cdd:smart00209    5 SEWSPCSVTCGGGVQTRTRSCCS--------PPPQNGGGPCTGEDVeTRACNEQPCP 53

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034591376   790 WHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFlnlsdELCQGPKASShKSCARTDCP 847
Cdd:smart00209    2 SEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGG-----GPCTGEDVET-RACNEQPCP 53

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20
                    ....*....|....*....|.
gi 1034591376   598 EPWSACSTTCGPGVQVREVKC 618
Cdd:smart00209    5 SEWSPCSVTCGGGVQTRTRSC 25

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1320 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1397
Cdd:cd20978      4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                           90
                   ....*....|...
gi 1034591376 1398 NALGKAVATSVLH 1410
Cdd:cd20978     75 NEIGDIYTETLLH 87

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034591376 1338 AALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1409
Cdd:cd04969     14 AAKGGDVIIECKPKASPKPTISWSKGTELLtnSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1336 VEAALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNG---SLLLQNVSLENEGTYVCIATNALGKAVATSVLH 1410
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrsSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034591376 1339 ALGANVTIRCPVKGVPQPNITWLKRGGSLSGN---VSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1409
Cdd:cd20952     12 AVGGTVVLNCQATGEPVPTISWLKDGVPLLGKderITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034591376 1338 AALGANVTIRCPVKGVPQPNITWLKRGGSLS-GNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1409
Cdd:cd05725      9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGELPkGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1335 IVE-----AALGANVTIRCPVKGVPQPNITWLKRGGSLSG---------NVSLLFNGSLLLQNVSLENEGTYVCIATNAL 1400
Cdd:cd20954      5 IVEpvdanVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGeykdllydpNVRILPNGTLVFGHVQKENEGHYLCEAKNGI 84

                   .
gi 1034591376 1401 G 1401
Cdd:cd20954     85 G 85

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1034591376 1628 WHTGPWKPCTAACGRGFQSRKVDCIHTRSCKPVAKRHCVQKKKPISWRHCLGPSC 1682
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQKKPPETQSCNLKPC 55

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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034591376 1333 GGIVEAALGANVTIRCPVKGVPQPNITWLKRGGS---LSGNVSLLFNGSLL-LQNVSLENEGTYVCIATNALGKAV 1404
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLiieFNTRYIVRENGTTLtIRNIRRSDMGIYLCIASNGVPGSV 84

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034591376 1340 LGANVTIRCPVKGVPQPNITWLKRG----GSLSGNVSLLFNGS-LLLQNVSLENEGTYVCIATNALG 1401
Cdd:cd05736     14 PGVEASLRCHAEGIPLPRVQWLKNGmdinPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034591376 1341 GANVTIRCPVKGVPQPNITWLKRGGSLSGNVSLL--FNGSLLLQNVSLENEGTYVCIATNALGKA 1403
Cdd:cd05731     10 GGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFenFNKTLKIENVSEADSGEYQCTASNTMGSA 74

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034591376 1338 AALGANVTIRCPVKGVPQPNITWLKRGGSL-SGNVSLLFN--GS-LLLQNVSLENEGTYVCIATNALGKAVATsvLHL 1411
Cdd:cd05730     15 ANLGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNedGSeMTILDVDKLDEAEYTCIAENKAGEQEAE--IHL 90

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034591376  956 SVIIKCPVRRFQKSLIQWEKDGRCLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIA----GSAQETVVL 1020
Cdd:cd04969     19 DVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAvnffGKANSTGSL 87

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034591376 1341 GANVTIRCPVKGVPQPNITWLKRGGSLSGNVS--LLF-NGSLLLQNVSLENEGTYVCIATNALGKAVATSVLHL 1411
Cdd:cd05764     15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSrtLVYdNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1034591376    78 WDAWGDWSDCSRTCGGGASYSLRRCLT------GRNCEGQNIRYKTCSNHDCP 124
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSpppqngGGPCTGEDVETRACNEQPCP 53

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034591376 1320 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGN--VSLLFNGSLLLQNVSLENEGTYVCIAT 1397
Cdd:cd20968      2 ITRPPTN---------VTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENnrIAVLESGSLRIHNVQKEDAGQYRCVAK 72

                           90
                   ....*....|.
gi 1034591376 1398 NALGKAVATSV 1408
Cdd:cd20968     73 NSLGIAYSKPV 83

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034591376 1455 WEPGNWSHCSATCGHlGARIQRPQCVMANGQE-VSEALCDHLQKPLAgFEPCNIRDC 1510
Cdd:pfam19030    1 WVAGPWGECSVTCGG-GVQTRLVQCVQKGGGSiVPDSECSAQKKPPE-TQSCNLKPC 55