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 145275198 1293 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1370
Cdd:cd20978     4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                          90
                  ....*....|...
gi 145275198 1371 NALGKAVATSVLH 1383
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 145275198   422 WEHNPWTACSVSCGGGIQRRSFVCVEEsmHGEILQVEEWkCMYAPKPKVMQTCNLFDC 479
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 145275198   129 DFRAQQCSAYNDVQYQ-----GHYYEW---LPrYNDPAAPCALKCHAQGQNLVVELAPKVLDGTRC------NTDSLDMC 194
Cdd:pfam19236    4 EFMSQQCARTDGQPLRsspggASFYHWgaaVP-HSQGDALCRHMCRAIGESFIMKRGDSFLDGTRCmpsgprEDGTLSLC 82

                           90       100       110
                   ....*....|....*....|....*....|...
gi 145275198   195 ISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTC 227
Cdd:pfam19236   83 VLGSCRTFGCDGRMDSQQVWDRCQVCGGDNSTC 115

PLAC (protease and lacunin) domain; The PLAC (protease and lacunin) domain is a short six-cysteine region that is usually found at the C terminal of proteins. It is found in a range of proteins including PACE4 (paired basic amino acid cleaving enzyme 4) and the extracellular matrix protein lacunin.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 145275198  1659 CTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQ 1689
Cdd:pfam08686    1 CKDKFANCSLVVQARLCSHKYYRQFCCRSCS 31

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   648 WEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMsQACNTEPC 703
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 145275198   763 WHIEEWQQCSRTCGGGTQNRRVTCRQLltdGSFLNLSDELCQG-PKASSHKSCARTDC 819
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQK---GGGSIVPDSECSAqKKPPETQSCNLKPC 55

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   482 WIAMEWSQCTVTCGRGLRYRVVLCI---NHRGEHVGGCNPQLKLHIKEECVIPiPC 534
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVqkgGGSIVPDSECSAQKKPPETQSCNLK-PC 55

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 145275198 1211 INILCDLITPSEATYTWTKDGTLLQPSVK---IILDGTGKIQIQNPTRKEQGIYECSVANHLGSDVESS 1276
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 145275198   343 WRQTDFFPCTVTCGGGYQLNSAECVDIRLKRVVPDHYChyypeNVKPKPKLKE-CSMDPC 401
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSEC-----SAQKKPPETQsCNLKPC 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 145275198 1293 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1370
Cdd:cd20978     4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                          90
                  ....*....|...
gi 145275198 1371 NALGKAVATSVLH 1383
Cdd:cd20978    75 NEIGDIYTETLLH 87

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145275198  1309 VEAALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNG---SLLLQNVSLENEGTYVCIATNALGKAVATSVLH 1383
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 145275198   422 WEHNPWTACSVSCGGGIQRRSFVCVEEsmHGEILQVEEWkCMYAPKPKVMQTCNLFDC 479
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 145275198   129 DFRAQQCSAYNDVQYQ-----GHYYEW---LPrYNDPAAPCALKCHAQGQNLVVELAPKVLDGTRC------NTDSLDMC 194
Cdd:pfam19236    4 EFMSQQCARTDGQPLRsspggASFYHWgaaVP-HSQGDALCRHMCRAIGESFIMKRGDSFLDGTRCmpsgprEDGTLSLC 82

                           90       100       110
                   ....*....|....*....|....*....|...
gi 145275198   195 ISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTC 227
Cdd:pfam19236   83 VLGSCRTFGCDGRMDSQQVWDRCQVCGGDNSTC 115

PLAC (protease and lacunin) domain; The PLAC (protease and lacunin) domain is a short six-cysteine region that is usually found at the C terminal of proteins. It is found in a range of proteins including PACE4 (paired basic amino acid cleaving enzyme 4) and the extracellular matrix protein lacunin.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 145275198  1659 CTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQ 1689
Cdd:pfam08686    1 CKDKFANCSLVVQARLCSHKYYRQFCCRSCS 31

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   648 WEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMsQACNTEPC 703
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 145275198   763 WHIEEWQQCSRTCGGGTQNRRVTCRQLltdGSFLNLSDELCQG-PKASSHKSCARTDC 819
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQK---GGGSIVPDSECSAqKKPPETQSCNLKPC 55

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   482 WIAMEWSQCTVTCGRGLRYRVVLCI---NHRGEHVGGCNPQLKLHIKEECVIPiPC 534
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVqkgGGSIVPDSECSAQKKPPETQSCNLK-PC 55

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 145275198 1211 INILCDLITPSEATYTWTKDGTLLQPSVK---IILDGTGKIQIQNPTRKEQGIYECSVANHLGSDVESS 1276
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145275198   929 SVIIKCPVRRFQKSLIQWEKDGRCLQNSKRLGITKSG---SLKIHGLAAPDIGVYRCIA----GSAQETVVLK 994
Cdd:pfam07679   17 SARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVAtnsaGEAEASAELT 89

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   570 PEPWSACSTTCGPGVQVREVKCRVLLTFTQTETELPEEEcegPKLPTERPCLLEAC 625
Cdd:pfam19030    3 AGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQ---KKPPETQSCNLKPC 55

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

                            10        20        30
                    ....*....|....*....|....*....|
gi 145275198    486 EWSQCTVTCGRGLRYRVVLCINHRGEHVGG 515
Cdd:smart00209    6 EWSPCSVTCGGGVQTRTRSCCSPPPQNGGG 35

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

                            10        20
                    ....*....|....*....|.
gi 145275198    426 PWTACSVSCGGGIQRRSFVCV 446
Cdd:smart00209    6 EWSPCSVTCGGGVQTRTRSCC 26

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 145275198    763 WHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFlnlsdELCQGPKASShKSCARTDCP 820
Cdd:smart00209    2 SEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGG-----GPCTGEDVET-RACNEQPCP 53

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145275198    929 SVIIKCPVRRFQKSLIQWEKDG-RCLQNSKRLGITKSG---SLKIHGLAAPDIGVYRCIA----GSAQETVVLK 994
Cdd:smart00410   11 SVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAAtnssGSASSGTTLT 84

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 145275198 1293 ITKPEHNhlsvvvggiVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNV--SLLFNGSLLLQNVSLENEGTYVCIAT 1370
Cdd:cd20978     4 IQKPEKN---------VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVAT 74

                          90
                  ....*....|...
gi 145275198 1371 NALGKAVATSVLH 1383
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 145275198 1311 AALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1382
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLtnSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145275198  1309 VEAALGANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNG---SLLLQNVSLENEGTYVCIATNALGKAVATSVLH 1383
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 145275198 1312 ALGANVTIRCPVKGVPQPNITWLKRGGSLSGN---VSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1382
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 145275198 1311 AALGANVTIRCPVKGVPQPNITWLKRGGSLS-GNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1382
Cdd:cd05725     9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGELPkGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 145275198   422 WEHNPWTACSVSCGGGIQRRSFVCVEEsmHGEILQVEEWkCMYAPKPKVMQTCNLFDC 479
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQK--GGGSIVPDSE-CSAQKKPPETQSCNLKPC 55

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 145275198  1601 WHTGPWKPCTAACGRGFQSRKVDCIHTRSCKPVAKRHCVQKKKPISWRHCLGPSC 1655
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 145275198 1306 GGIVEAALGANVTIRCPVKGVPQPNITWLKRGGS---LSGNVSLLFNGSLL-LQNVSLENEGTYVCIATNALGKAV 1377
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLiieFNTRYIVRENGTTLtIRNIRRSDMGIYLCIASNGVPGSV 84

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 145275198   129 DFRAQQCSAYNDVQYQ-----GHYYEW---LPrYNDPAAPCALKCHAQGQNLVVELAPKVLDGTRC------NTDSLDMC 194
Cdd:pfam19236    4 EFMSQQCARTDGQPLRsspggASFYHWgaaVP-HSQGDALCRHMCRAIGESFIMKRGDSFLDGTRCmpsgprEDGTLSLC 82

                           90       100       110
                   ....*....|....*....|....*....|...
gi 145275198   195 ISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTC 227
Cdd:pfam19236   83 VLGSCRTFGCDGRMDSQQVWDRCQVCGGDNSTC 115

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 145275198  1487 WFTSVWSQCSVSCGEGYHSRQVTCKRTKANGtvqVVSPRACAPKDRPLGRKPCFGHPC 1544
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGS---IVPDSECSAQKKPPETQSCNLKPC 55

PLAC (protease and lacunin) domain; The PLAC (protease and lacunin) domain is a short six-cysteine region that is usually found at the C terminal of proteins. It is found in a range of proteins including PACE4 (paired basic amino acid cleaving enzyme 4) and the extracellular matrix protein lacunin.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 145275198  1659 CTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQ 1689
Cdd:pfam08686    1 CKDKFANCSLVVQARLCSHKYYRQFCCRSCS 31

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145275198 1314 GANVTIRCPVKGVPQPNITWLKRGGSL--SGNVSLLFNGSLLLQNVSL-ENEGTYVCIATN 1371
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRLplNHRQRVFPNGTLVIENVQRsSDEGEYTCTARN 75

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145275198 1309 VEAALGANVTIRCPVKGVPQPNITWLKrGGSL---SGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVL 1382
Cdd:cd05852    12 ILAAKGGRVIIECKPKAAPKPKFSWSK-GTELlvnNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVL 87

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198 1309 VEAALGANVTIRCPVKG-VPQPNITWLKRGGSLSGNvSLLFNGSLLLQNVSLENEGTYVCIATNALGKAVATSVLH 1383
Cdd:cd05754    11 QEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPSR-AMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEATATLY 85

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 145275198   648 WEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMsQACNTEPC 703
Cdd:pfam19030    1 WVAGPWGECSVTCGGGVQTRLVQCVQKGGGSIVPDSECSAQKKPPET-QSCNLKPC 55