NCBI Conserved Domain Search

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

Pssm-ID: 409486 Cd Length: 101 Bit Score: 198.92 E-value: 1.22e-60

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 404 PEDPVIKMSGPLVHGRPVTVNCTVPNVYPFDHLEIELLKGETTLMKKYFLEEMGIKSLETKILETTFIPTIEDTGKSLVC 483
Cdd:cd07689    1 PKDPEIEMSGPLVAGKPVTVSCSVPDVYPFDRLEIELLKGETLLESKEFLEDMDKKSLETKSLEVTFIPTIEDTGKVLVC 80

                         90       100
                 ....*....|....*....|.
gi 170295823 484 LARLHSGEMESEPKQRQSVQP 504
Cdd:cd07689   81 RAKLHIDEMEFEPKQRQSTQE 101

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of VCAM-1 is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 176.32 E-value: 1.66e-52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 313 FIVDISPGSQVAAQVGDSVVLTCAAIGCDSPSFSWRTQTDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLCAVTCLQRTL 392
Cdd:cd20943    1 FKVEISPGSRYAAQIGDSVSLTCSTTGCESPSFSWRTQIDSPLNGKVRNEGTTSTLTLSPVSFENEHSYLCTVTCESRKL 80


                 ....*....
gi 170295823 393 EKRTQVEVY 401
Cdd:cd20943   81 EKGIQVEIY 89

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

Pssm-ID: 409486 Cd Length: 101 Bit Score: 159.24 E-value: 4.12e-46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 116 PKDPEIQFSGPLEVGKPVTVKCLAPDIYPVYRLEIDLFKGDQLMNRQEFSSEEMTKSLETKSLEVTFTPVIEDIGKALVC 195
Cdd:cd07689    1 PKDPEIEMSGPLVAGKPVTVSCSVPDVYPFDRLEIELLKGETLLESKEFLEDMDKKSLETKSLEVTFIPTIEDTGKVLVC 80

                         90       100
                 ....*....|....*....|.
gi 170295823 196 RAKLHIDQIDSTLKERETVKE 216
Cdd:cd07689   81 RAKLHIDEMEFEPKQRQSTQE 101

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of VCAM-1 is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 149.35 E-value: 1.30e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  25 FKIEISPEYKTIAQIGDSMALTCSTTGCESPLFSWRTQIDSPLNAKVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKL 104
Cdd:cd20943    1 FKVEISPGSRYAAQIGDSVSLTCSTTGCESPSFSWRTQIDSPLNGKVRNEGTTSTLTLSPVSFENEHSYLCTVTCESRKL 80


                 ....*....
gi 170295823 105 ERSIHVDIY 113
Cdd:cd20943   81 EKGIQVEIY 89

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

Pssm-ID: 409368 Cd Length: 88 Bit Score: 77.88 E-value: 1.70e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 606 TVFPSKSVKEGDTVIISCTCG--NVPETWIILKKKAKT---GDMVLKSvDGSYTIRQAQLQDAGIYECESKTEV-GSQLR 679
Cdd:cd04979    1 TSFKQISVKEGDTVILSCSVKsnNAPVTWIHNGKKVPRyrsPRLVLKT-ERGLLIRSAQEADAGVYECHSGERVlGSTLR 79


                 ....*.
gi 170295823 680 SLTLDV 685
Cdd:cd04979   80 SVTLHV 85

Immunoglobulin C2-set domain;

Pssm-ID: 399065 Cd Length: 80 Bit Score: 76.23 E-value: 5.06e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  133 VTVKCLApDIYPVYRLEIDLFKGdQLMNRQEFSSEEMTKSLETKSLEVTFTPVIEDIGkALVCRAKlhidqiDSTLKERE 212
Cdd:pfam05790   1 VTVSCSN-NLLTCEVLELTLPKG-SKMDPSLKLKGQEAKSLETKKLESTFQPTTEDSG-TWVCLAS------DNDQKKLE 71


                  ....*....
gi 170295823  213 TVKELQVYI 221
Cdd:pfam05790  72 SVIEVLVLE 80

Immunoglobulin C2-set domain;

Pssm-ID: 399065 Cd Length: 80 Bit Score: 74.30 E-value: 2.08e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  421 VTVNCTVpNVYPFDHLEIELLKGeTTLMKKYFLEEMGIKSLETKILETTFIPTIEDTGkSLVCLARlhsgemESEPKQRQ 500
Cdd:pfam05790   1 VTVSCSN-NLLTCEVLELTLPKG-SKMDPSLKLKGQEAKSLETKKLESTFQPTTEDSG-TWVCLAS------DNDQKKLE 71


                  ....*....
gi 170295823  501 SVQPLYVNV 509
Cdd:pfam05790  72 SVIEVLVLE 80

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 65.22 E-value: 5.01e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823   321 SQVAAQVGDSVVLTCAAIGCDSPSFSWRTQTDSPL----NGVVRNEGAKSTLVLSSVGFEDEHSYLCAVTCLQRTLEKRT 396
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesgRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 170295823   397 QVEV 400
Cdd:smart00410  82 TLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 60.35 E-value: 2.69e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  321 SQVAAQVGDSVVLTCAAIGCDSPSFSWRTQtDSPLN----GVVRNEGAKSTLVLSSVGFEDEHSYLCAVTCLQRTLEKRT 396
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKD-GQPLRssdrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                  ....
gi 170295823  397 QVEV 400
Cdd:pfam07679  87 ELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.89 E-value: 2.71e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823  515 TIWVSPSP-ILEEGSPVNLTCSSDGIPAPKILWSRqlNNGELQPLS--------ENTTLTFMSTKRDDSGIYVCEGIN 583
Cdd:pfam13927   3 VITVSPSSvTVREGETVTLTCEATGSPPPTITWYK--NGEPISSGStrsrslsgSNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 59.83 E-value: 3.55e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823   232 PSTRLQEGGAVTMTCSSEGLPAPEIFWgRKLDNEVLQL--------LSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAE 303
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTW-YKQGGKLLAEsgrfsvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                   ....*
gi 170295823   304 VELVV 308
Cdd:smart00410  81 TTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.19 E-value: 6.22e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823   37 AQIGDSMALTCSTTGCESPLFSWRTQiDSPLNA----KVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIHV 110
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDPEVSWFKD-GQPLRSsdrfKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 1.08e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823  227 TISVHPS-TRLQEGGAVTMTCSSEGLPAPEIFW---GRKLDNEVLQ---LLSGNATLTLIAMRMEDSGVYVCEGVN 295
Cdd:pfam13927   3 VITVSPSsVTVREGETVTLTCEATGSPPPTITWyknGEPISSGSTRsrsLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 58.29 E-value: 1.21e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823   519 SPSPILEEGSPVNLTCSSDGIPAPKILWSRQL-------NNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKS 591
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGgkllaesGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                   ....*
gi 170295823   592 VELII 596
Cdd:smart00410  81 TTLTV 85

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.90 E-value: 1.60e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823    35 TIAQIGDSMALTCSTTGCESPLFSWRTQIDSPL----NAKVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIHV 110
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesgRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 57.40 E-value: 2.87e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 237 QEGGAVTMTCSSEGLPAPEIFW---GRKLDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd20978   14 KGGQDVTLPCQVTGVPQPKITWlhnGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 54.32 E-value: 3.00e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 515 TIWVSPSPILEEGSPVNLTCSSDGIPApKILWSRqlNNGELQP-----LSE-NTTLTFMSTKRDDSGIYVCEGINEAGIS 588
Cdd:cd05740    3 FISSNNSNPVEDKDAVTLTCEPETQNT-SYLWWF--NGQSLPVtprltLSNgNRTLTLLNVTREDAGAYQCEISNPVSAN 79


                 .
gi 170295823 589 R 589
Cdd:cd05740   80 R 80

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 54.51 E-value: 3.06e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  229 SVHPSTRLQEGGAVTMTCS-SEGLPAPEIFWGRKLDNEVLQLL-------SGNATLTLIAMRMEDSGVYVCEGVNLIGRD 300
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSaSTGSPGPDVTWSKEGGTLIESLKvkhdngrTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                  ....*.
gi 170295823  301 KAEVEL 306
Cdd:pfam00047  81 TLSTSL 86

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 53.10 E-value: 5.10e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 242 VTMTCSSEGLPAPEIFW---GRKLDNEVLQ---LLSGNATLTLIAMRMEDSGVYVCEGVNLIGR 299
Cdd:cd00096    1 VTLTCSASGNPPPTITWyknGKPLPPSSRDsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.42 E-value: 6.27e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823  526 EGSPVNLTCSSDGIPAPKILWSRqlNNGELQPLSE--------NTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:pfam07679  14 EGESARFTCTVTGTPDPEVSWFK--DGQPLRSSDRfkvtyeggTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 53.28 E-value: 7.22e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILWSRqlNNGELQPLSEN-------TTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd20970   13 TAREGENATFMCRAEGSPEPEISWTR--NGNLIIEFNTRyivrengTTLTIRNIRRSDMGIYLCIASNGVP 81

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 52.78 E-value: 9.06e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  514 TTIWVSPSPIlEEGSPVNLTCSSDGIPAPKILWSRqlnNGElqPLSENTTLTFMSTKRDDSGIYVCEGINEAG-ISRKSV 592
Cdd:pfam13895   2 PVLTPSPTVV-TEGEPVTLTCSAPGNPPPSYTWYK---DGS--AISSSPNFFTLSVSAEDSGTYTCVARNGRGgKVSNPV 75


                  ....
gi 170295823  593 ELII 596
Cdd:pfam13895  76 ELTV 79

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 52.33 E-value: 1.02e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 530 VNLTCSSDGIPAPKILWSRqlNNGELQP--------LSENTTLTFMSTKRDDSGIYVCEGINEAGISRKS 591
Cdd:cd00096    1 VTLTCSASGNPPPTITWYK--NGKPLPPssrdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 52.78 E-value: 1.14e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823 525 EEGSPVNLTCSSDGIPAPKILWsrqLNNG-ELQPLSENT-----TLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd20978   14 KGGQDVTLPCQVTGVPQPKITW---LHNGkPLQGPMERAtvedgTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.57 E-value: 1.17e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823  311 KPFIVdiSPGSQVAAQVGDSVVLTCAAIGCDSPSFSWR---TQTDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLCAVT 386
Cdd:pfam13927   1 KPVIT--VSPSSVTVREGETVTLTCEATGSPPPTITWYkngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 52.09 E-value: 1.87e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 519 SPSPILEEGSPVNLTCSSDGIPAPKILW----SRQLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd05764    7 THELRVLEGQRATLRCKARGDPEPAIHWispeGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVEL 86


                 ..
gi 170295823 595 II 596
Cdd:cd05764   87 HI 88

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 52.14 E-value: 2.58e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFWGRKLDN--EVLQLLSGN---------ATLTLIAMRMEDSGVYVCEGVNLIGRD 300
Cdd:cd05732   15 ELEQITLTCEAEGDPIPEITWRRATRGisFEEGDLDGRivvrgharvSSLTLKDVQLTDAGRYDCEASNRIGGD 88

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

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 50.24 E-value: 8.26e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 239 GGAVTMTCSSEGLPAPEIFWgRKLDNEVL---QLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVVQ 309
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKW-RKVDGSPSsqwEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 49.95 E-value: 1.02e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823  237 QEGGAVTMTCSSEGLPAPEIFW---GRKL--DNEVLQLLSGN-ATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:pfam07679  13 QEGESARFTCTVTGTPDPEVSWfkdGQPLrsSDRFKVTYEGGtYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 49.12 E-value: 1.98e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  518 VSPSPILEEGSPVNLTCS-SDGIPAPKILWSR---QLNNGELQPLSEN----TTLTFMSTKRDDSGIYVCEGINEAGISR 589
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSaSTGSPGPDVTWSKeggTLIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                  ....*
gi 170295823  590 KSVEL 594
Cdd:pfam00047  82 LSTSL 86

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 48.86 E-value: 2.89e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 234 TRLQEGGAVTMTCSSEGLPAPEIFWGRKLDN--EVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVVQ 309
Cdd:cd05851   11 TYALKGQNVTLECFALGNPVPVIRWRKILEPmpATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 48.63 E-value: 3.34e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 228 ISVH-PSTRLQEGGAVTMTCSSEGLPAPEIFW----GRKLDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKA 302
Cdd:cd05764    3 ITRHtHELRVLEGQRATLRCKARGDPEPAIHWispeGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATA 82


                 ....*.
gi 170295823 303 EVELVV 308
Cdd:cd05764   83 RVELHI 88

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 48.85 E-value: 3.76e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRQLNN--GELQPLS--------ENTTLTFMSTKRDDSGIYVCEGINE--AGISrksvel 594
Cdd:cd20954   16 GQDVMLHCQADGFPTPTVTWKKATGStpGEYKDLLydpnvrilPNGTLVFGHVQKENEGHYLCEAKNGigSGLS------ 89

                         90
                 ....*....|...
gi 170295823 595 iiqvspKDIQLTV 607
Cdd:cd20954   90 ------KVIFLKV 96

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 47.88 E-value: 5.50e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 222 SPRNTTISVhpstrlqeGGAVTMTCSSEGLPAPEIFW---GRKL--DNEVLQLLSgNATLTLIAMRMEDSGVYVCEGVNL 296
Cdd:cd20952    5 GPQNQTVAV--------GGTVVLNCQATGEPVPTISWlkdGVPLlgKDERITTLE-NGSLQIKGAEKSDTGEYTCVALNL 75

                         90
                 ....*....|..
gi 170295823 297 IGRDKAEVELVV 308
Cdd:cd20952   76 SGEATWSAVLDV 87

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

Pssm-ID: 409579 Cd Length: 94 Bit Score: 48.34 E-value: 5.54e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 119 PEIQFSGPLEVGKPVTVKCLAPDIYPVYRLEIDLFKGDQLMNRQEFSSEEMTKSLeTKSLEVTFTPVIEDIGKALVCRAK 198
Cdd:cd20987    1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWLGAALTPLPPVLGRLEEEGTT-THSSVLTFTPRPEDHGTNLTCQVK 79

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 47.77 E-value: 5.91e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 225 NTTISVHPSTRLQEGGAVTMTCSSEGLPApEIFWGRK----LDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRD 300
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNT-SYLWWFNgqslPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSAN 79


                 ....*....
gi 170295823 301 KAE-VELVV 308
Cdd:cd05740   80 RSDpVTLDV 88

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 51.94 E-value: 5.91e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 526 EGSPVNLTCS-----SDGIPAPKILWS-RQLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL-IIQV 598
Cdd:PHA02785  40 ENEPVILPCPqintlSSGYNILDILWEkRGADNDRIIPIDNGSNMLILNPTQSDSGIYICITKNETYCDMMSLNLtIVSV 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 599 SPKDIQLTVFPsKSVKEGDTVIISC------TCGNVPETWIILKKKAKTGDMVLKSVDGSYTIRQAQLQDAGIYECESKT 672
Cdd:PHA02785 120 SESNIDLISYP-QIVNERSTGEMVCpninafIASNVNADIIWSGHRRLRNKRLKQRTPGIITIEDVRKNDAGYYTCVLKY 198

                        170
                 ....*....|....
gi 170295823 673 EVGSQLRSLTLDVK 686
Cdd:PHA02785 199 IYGDKTYNVTRIVK 212

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 47.50 E-value: 6.83e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823   609 PSKSVKEGDTVIISCTCGNVPETWIILKKKAKT-----GDMVLKSVDG--SYTIRQAQLQDAGIYECESKTEVGSQLRSL 681
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKllaesGRFSVSRSGStsTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 170295823   682 TLDV 685
Cdd:smart00410  82 TLTV 85

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 48.05 E-value: 7.57e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFWGRKLDN--------------EVlQLLSGNATLTLIAMRMEDSGVYVCEGVNLIG 298
Cdd:cd05870   15 ENGAATLSCKAEGEPIPEITWKRASDGhtfsegdkspdgriEV-KGQHGESSLHIKDVKLSDSGRYDCEAASRIG 88

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 47.50 E-value: 8.96e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFWGR-----KLDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVN-LIGRDKAEVELVV 308
Cdd:cd20970   16 EGENATFMCRAEGSPEPEISWTRngnliIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNgVPGSVEKRITLQV 92

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

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 47.49 E-value: 9.25e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRqlNNGELQPLSENT---------TLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd05744   14 EGRLCRFDCKVSGLPTPDLFWQL--NGKPVRPDSAHKmlvrengrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 46.87 E-value: 1.37e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 228 ISVHPSTRLQEGG-AVTMTCSSEGLPAPEIFW-------GRKLDNEvLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGR 299
Cdd:cd05736    3 IRVYPEFQAKEPGvEASLRCHAEGIPLPRVQWlkngmdiNPKLSKQ-LTLIANGSELHISNVRYEDTGAYTCIAKNEGGV 81

                         90
                 ....*....|.
gi 170295823 300 DKAEVELVVQE 310
Cdd:cd05736   82 DEDISSLFVED 92

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

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 47.11 E-value: 1.42e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 233 STRLQEGGAVTMTCSSEGLPAPEIFWgrKLDNEVLQLLS---------GNATLTLIAMRMEDSGVYVCEGVNLIGRDKAE 303
Cdd:cd05744    9 DLEVQEGRLCRFDCKVSGLPTPDLFW--QLNGKPVRPDSahkmlvrenGRHSLIIEPVTKRDAGIYTCIARNRAGENSFN 86


                 ....*
gi 170295823 304 VELVV 308
Cdd:cd05744   87 AELVV 91

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 46.67 E-value: 1.89e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 517 WVSPSP--ILEEGSPVNLTCSSDGIPAPKILWSrqLNNGELQPLSEN-------TTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd04978    2 WIIEPPslVLSPGETGELICEAEGNPQPTITWR--LNGVPIEPAPEDmrrtvdgRTLIFSNLQPNDTAVYQCNASNVHG 78

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

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 46.03 E-value: 2.68e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRqlnngELQPLSE------------NTTLTFMSTKRDDSGIYVCEGINEAGISRKSVE 593
Cdd:cd20973   11 EGSAARFDCKVEGYPDPEVKWMK-----DDNPIVEsrrfqidqdedgLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                 ...
gi 170295823 594 LII 596
Cdd:cd20973   86 LTV 88

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

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 45.66 E-value: 3.00e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILWSRqlNNGELQPL--------SENTTLTFMSTKRDDSGIYVCEGINEAGIsrKSVEL 594
Cdd:cd05748    3 VVRAGESLRLDIPIKGRPTPTVTWSK--DGQPLKETgrvqiettASSTSLVIKNAKRSDSGKYTLTLKNSAGE--KSATI 78


                 ....
gi 170295823 595 IIQV 598
Cdd:cd05748   79 NVKV 82

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 45.31 E-value: 3.25e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFWGR-----KLDNEVLQLLSGnaTLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKggsqlSVDRRHLVLSSG--TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 45.25 E-value: 3.62e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823   26 KIEISPEyKTIAQIGDSMALTCSTTGCESPLFSWR---TQIDSPLNAKVRTEGSKSVLTMEPVSFENEHSYLCTAT 98
Cdd:pfam13927   3 VITVSPS-SVTVREGETVTLTCEATGSPPPTITWYkngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.72 E-value: 3.83e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 525 EEGSPVNLTCSSDGIPAPKILWsrqLNNGE---------LQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELI 595
Cdd:cd05736   13 EPGVEASLRCHAEGIPLPRVQW---LKNGMdinpklskqLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLF 89


                 ....
gi 170295823 596 IQVS 599
Cdd:cd05736   90 VEDS 93

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 45.65 E-value: 4.08e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 233 STRLQEGGAVTMTCSSEGLPAPEIFW---GRKLDNEV-LQLLSGNATLTLIAMRM--EDSGVYVCEGVNLIGRDKAEVEL 306
Cdd:cd20972   10 SQEVAEGSKVRLECRVTGNPTPVVRWfceGKELQNSPdIQIHQEGDLHSLIIAEAfeEDTGRYSCLATNSVGSDTTSAEI 89


                 ..
gi 170295823 307 VV 308
Cdd:cd20972   90 FV 91

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

Pssm-ID: 409473 Cd Length: 92 Bit Score: 45.53 E-value: 4.28e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSR-----QLNNGELQPLSENT---TLTFMSTKRDDSGIYVCEGINEAGIS 588
Cdd:cd05892   14 EGDPVRLECQISAIPPPQIFWKKnnemlQYNTDRISLYQDNCgriCLLIQNANKKDAGWYTVSAVNEAGVV 84

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 45.36 E-value: 5.33e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 170295823 321 SQVAAQVGDSVVLTCAAIGCDSPSFSWRTQT------DSPLNG--VVRNEGAKSTLVLSSVGFEDEHSYLC 383
Cdd:cd05869   10 NQTAMELEEQITLTCEASGDPIPSITWRTSTrnisseEKTLDGhiVVRSHARVSSLTLKYIQYTDAGEYLC 80

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 44.79 E-value: 6.71e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRQ----LNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd20952   14 GGTVVLNCQATGEPVPTISWLKDgvplLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

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

Pssm-ID: 409416 Cd Length: 98 Bit Score: 44.75 E-value: 8.45e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 513 ETTIWVSPSPILEEGSPVNLTCSSDGI-PAPKILWSRqlnNGELQ--------------PLSENTTLTFMSTKRDDSGIY 577
Cdd:cd05759    1 DPVIEGGPVISLQAGVPYNLTCRARGAkPAAEIIWFR---DGEQLegavyskellkdgkRETTVSTLLITPSDLDTGRTF 77

                         90
                 ....*....|....*....
gi 170295823 578 VCEGINEA--GISRKSVEL 594
Cdd:cd05759   78 TCRARNEAipNGKETSITL 96

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 44.95 E-value: 9.78e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 218 QVYISPRNTTISvhpstrlqEGGAVTMTCSSEGLPAPEIFWGRK------LDNEVLQ-----LLSGNATLTLIAMRMEDS 286
Cdd:cd05726    1 QFVVKPRDQVVA--------LGRTVTFQCETKGNPQPAIFWQKEgsqnllFPYQPPQpssrfSVSPTGDLTITNVQRSDV 72

                         90       100
                 ....*....|....*....|....
gi 170295823 287 GVYVCEGVNLIGRDKAEVELVVQE 310
Cdd:cd05726   73 GYYICQALNVAGSILAKAQLEVTD 96

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 43.63 E-value: 1.53e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 527 GSPVNLTCSSDGIPAPKILWsrQLNNG------ELQPLSENT--TLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd05743    1 GETVEFTCVATGVPTPIINW--RLNWGhvpdsaRVSITSEGGygTLTIRDVKESDQGAYTCEAINTRG 66

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 43.54 E-value: 1.73e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRqlNNGELqPLS-----ENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd05725   12 DDSAEFQCEVGGDPVPTVRWRK--EDGEL-PKGryeilDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.36 E-value: 2.09e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 170295823 232 PSTRL--QEGGAVTMTCSSEGLPAPEIFWGR---KLDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIG 298
Cdd:cd05876    1 SSSSLvaLRGQSLVLECIAEGLPTPTVKWLRpsgPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLG 72

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 43.17 E-value: 2.35e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 239 GGAVTMTCSSEGLPAPEIFWGRK---LDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVVQ 309
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLggeLPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTVE 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 42.94 E-value: 2.59e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 170295823  604 QLTVFPSKS-VKEGDTVIISCTCGNVPE---TWIILKKKAKTGDMVLKSVD---GSYTIRQAQLQDAGIYECE 669
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATGSPPptiTWYKNGEPISSGSTRSRSLSgsnSTLTISNVTRSDAGTYTCV 75

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 43.43 E-value: 3.24e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 223 PRNTTISVHPSTRLQEggAVTMTCSSEGLPAPEIFW--GRKLDNEVLQLLSGN---------ATLTLIAMRMEDSGVYVC 291
Cdd:cd05869    3 PKITYVENQTAMELEE--QITLTCEASGDPIPSITWrtSTRNISSEEKTLDGHivvrsharvSSLTLKYIQYTDAGEYLC 80

                         90
                 ....*....|....*..
gi 170295823 292 EGVNLIGRDKAEVELVV 308
Cdd:cd05869   81 TASNTIGQDSQSMYLEV 97

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

Pssm-ID: 409372 [Multi-domain] Cd Length: 109 Bit Score: 43.41 E-value: 3.27e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 231 HPSTRLQEGGAVTMTCSSEGLPAPEIFWGRKLDNEVLQLL------SGNA----------------TLTLIAMRMEDSGV 288
Cdd:cd04983    5 PQSLSVQEGENVTLNCNYSTSTFYYLFWYRQYPGQGPQFLiyissdSGNKkkgrfsatldksrkssSLHISAAQLSDSAV 84


                 ...
gi 170295823 289 YVC 291
Cdd:cd04983   85 YFC 87

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 42.77 E-value: 3.31e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 223 PRNTTISVhpstrlqeGGAVTMTCSSEGLPAPEIFWgRKLDNEV----LQLLSGNaTLTLIAMRMEDSGVYVCEGVNLIG 298
Cdd:cd05725    4 PQNQVVLV--------DDSAEFQCEVGGDPVPTVRW-RKEDGELpkgrYEILDDH-SLKIRKVTAGDMGSYTCVAENMVG 73

                         90
                 ....*....|
gi 170295823 299 RDKAEVELVV 308
Cdd:cd05725   74 KIEASATLTV 83

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 42.48 E-value: 4.20e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 239 GGAVTMTCSSEGLPAPEIFW----GRKLDNEVLQLLS--GNATLTLIAMRMEDSGVYVCEGVNLIGR 299
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWrlnwGHVPDSARVSITSegGYGTLTIRDVKESDQGAYTCEAINTRGM 67

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 42.52 E-value: 4.74e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 504 PLYVNVAPkettiwvsPSPILEEGSPVNLTCSSDGIPAPKILW---SRQL-NNGELQPLSENTtLTFMSTKRDDSGIYVC 579
Cdd:cd20957    1 PLSATIDP--------PVQTVDFGRTAVFNCSVTGNPIHTVLWmkdGKPLgHSSRVQILSEDV-LVIPSVKREDKGMYQC 71

                         90
                 ....*....|....*
gi 170295823 580 EGINEAGISRKSVEL 594
Cdd:cd20957   72 FVRNDGDSAQATAEL 86

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 42.64 E-value: 4.98e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILWSRQ------LNNGELQP-----LSENTTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd05726   10 VVALGRTVTFQCETKGNPQPAIFWQKEgsqnllFPYQPPQPssrfsVSPTGDLTITNVQRSDVGYYICQALNVAG 84

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 42.11 E-value: 6.20e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 312 PFIVDISPGSQVAAQVGDSVVLTCAAIGCDSPSFSWRTqtdsplNGVVRNEGAK--------STLVLSSVGFEDEHSYLC 383
Cdd:cd20970    1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTR------NGNLIIEFNTryivrengTTLTIRNIRRSDMGIYLC 74

                         90
                 ....*....|....*...
gi 170295823 384 -AVTCLQRTLEKRTQVEV 400
Cdd:cd20970   75 iASNGVPGSVEKRITLQV 92

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

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.39 E-value: 6.34e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 236 LQEGGAVTMTCSSEGLPAPEIFW---GRKL--DNEVLQLLSGNATLTLI--AMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd20990   12 VQEGKLCRMDCKVSGLPTPDLSWqldGKPIrpDSAHKMLVRENGVHSLIiePVTSRDAGIYTCIATNRAGQNSFNLELVV 91

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

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 41.79 E-value: 8.77e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFWgRKLDNEVL--------QLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd20973   11 EGSAARFDCKVEGYPDPEVKW-MKDDNPIVesrrfqidQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

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

Pssm-ID: 409442 Cd Length: 92 Bit Score: 41.77 E-value: 9.33e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 527 GSPVNLTCSSDGIPAPKILW----SRQLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWlkdnKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

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

Pssm-ID: 409418 Cd Length: 102 Bit Score: 42.03 E-value: 9.48e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 509 VAPKETTIWVSPSPILEeGSPVNLTC-SSDGIPAPKILWSRqlNNGELQPLSE------------NTTLTFMSTKRDDSG 575
Cdd:cd05761    2 GVPEKPVITGFTSPVVE-GDEITLTCtTSGSKPAADIRWFK--NDKELKGVKEvqesgagktftvTSTLRFRVDRDDDGV 78

                         90
                 ....*....|
gi 170295823 576 IYVCEGINEA 585
Cdd:cd05761   79 AVICRVDHES 88

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.85 E-value: 9.63e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 228 ISVHPSTRLQEGGAVTMTCSSEGLPAPEIFW---GRKL--DNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKA 302
Cdd:cd20976    5 SSVPKDLEAVEGQDFVAQCSARGKPVPRITWirnAQPLqyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSC 84


                 ....*.
gi 170295823 303 EVELVV 308
Cdd:cd20976   85 SAWVTV 90

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 41.61 E-value: 1.02e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 525 EEGSPVNLTCSSDGIPAPKILW-SRQLN------NGELQPLSENtTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd20969   15 DEGHTVQFVCRADGDPPPAILWlSPRKHlvsaksNGRLTVFPDG-TLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 41.23 E-value: 1.17e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 230 VHPS-TRLQEGGAVTMTCSS-EGLPAPEIFWgRK------LDNEVLQLLSGnATLTLIAMRMEDSGVYVCEGVNLIG-RD 300
Cdd:cd05724    2 VEPSdTQVAVGEMAVLECSPpRGHPEPTVSW-RKdgqplnLDNERVRIVDD-GNLLIAEARKSDEGTYKCVATNMVGeRE 79


                 ....*...
gi 170295823 301 KAEVELVV 308
Cdd:cd05724   80 SRAARLSV 87

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 1.28e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 170295823  318 SPGSQVAAQVGDSVVLTCAAIGCDS-PSFSWRTQTDSPLNG--VVRNEG--AKSTLVLSSVGFEDEHSYLCAV 385
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPgPDVTWSKEGGTLIESlkVKHDNGrtTQSSLLISNVTKEDAGTYTCVV 73

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 41.47 E-value: 1.30e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  613 VKEGDTVIISCTCGNVPE---TWiiLKKKAK---TGDMVLKSVDGSYT--IRQAQLQDAGIYECESKTEVGSQLRSLTLD 684
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDpevSW--FKDGQPlrsSDRFKVTYEGGTYTltISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                  .
gi 170295823  685 V 685
Cdd:pfam07679  90 V 90

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

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.38 E-value: 1.47e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 227 TISVHPSTR-LQEGGAVTMTCSSEGLPAPEIFWGRKLDNEVLQLLS-----GNATLTLIAM------RMEDSGVYVCEGV 294
Cdd:cd05765    2 ALVNSPTHQtVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRpnhvrGNVVVTNIGQlviynaQPQDAGLYTCTAR 81

                         90
                 ....*....|....
gi 170295823 295 NLIGRDKAEVELVV 308
Cdd:cd05765   82 NSGGLLRANFPLSV 95

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.08 E-value: 1.54e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRqlNNGELQPLSENTT-------LTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd20976   15 EGQDFVAQCSARGKPVPRITWIR--NAQPLQYAADRSTceagvgeLHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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

Pssm-ID: 409442 Cd Length: 92 Bit Score: 41.00 E-value: 1.76e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 239 GGAVTMTCSSEGLPAPEIFW---GRKLDN-EVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWlkdNKPLTPpEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 40.94 E-value: 1.82e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 239 GGAVTMTCSSEGLPAPEIFWGRK------------LDNEVLQLLsGNATLTLIAMRMEDSGVYVCEGVNLIGRD 300
Cdd:cd05734   16 GKAVVLNCSADGYPPPTIVWKHSkgsgvpqfqhivPLNGRIQLL-SNGSLLIKHVLEEDSGYYLCKVSNDVGAD 88

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

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 41.07 E-value: 1.92e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 527 GSPVNLTCSSDGIPAPKILWsrQLNNGELQP---------LSENTTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd05763   14 GSTARLECAATGHPTPQIAW--QKDGGTDFPaarerrmhvMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

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

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 40.68 E-value: 2.14e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 223 PRNTTISVHPSTRLQeggavtmtCSSEGLPAPEIFWGRKLDNEV-------LQLLSGNATLTLIAMRMEDSGVYVCEGVN 295
Cdd:cd05763    6 PHDITIRAGSTARLE--------CAATGHPTPQIAWQKDGGTDFpaarerrMHVMPEDDVFFIVDVKIEDTGVYSCTAQN 77

                         90
                 ....*....|...
gi 170295823 296 LIGRDKAEVELVV 308
Cdd:cd05763   78 SAGSISANATLTV 90

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 40.84 E-value: 2.34e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 238 EGGAVTMTCSSEGLPAPEIFW---GRKL----DNEVLQLLSGnATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWlspRKHLvsakSNGRLTVFPD-GTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 40.55 E-value: 2.50e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 170295823 527 GSPVNLTCSSDGIPAPKILW--SRQLNNGELQP---------LSENTTLTFMSTKRDDSGIYVCEGINEAG 586
Cdd:cd05734   16 GKAVVLNCSADGYPPPTIVWkhSKGSGVPQFQHivplngriqLLSNGSLLIKHVLEEDSGYYLCKVSNDVG 86

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 40.73 E-value: 2.69e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  32 EYKTIAQIGDSMALTCSTTGCESPLFSWRTQI------DSPLNAK--VRTEGSKSVLTMEPVSFENEHSYLCTATCGSGK 103
Cdd:cd05869    9 ENQTAMELEEQITLTCEASGDPIPSITWRTSTrnisseEKTLDGHivVRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQ 88


                 ....*....
gi 170295823 104 LERSIHVDI 112
Cdd:cd05869   89 DSQSMYLEV 97

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 40.59 E-value: 2.77e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRQLNNG-----------ELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd05732   15 ELEQITLTCEAEGDPIPEITWRRATRGIsfeegdldgriVVRGHARVSSLTLKDVQLTDAGRYDCEASNRIGGDQQSMYL 94


                 ..
gi 170295823 595 II 596
Cdd:cd05732   95 EV 96

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

Pssm-ID: 409582 Cd Length: 91 Bit Score: 40.47 E-value: 3.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 524 LEEGSPVNLTCSSDGIPAPKILWsrQLNNGELQPLSENT---------TLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd20990   12 VQEGKLCRMDCKVSGLPTPDLSW--QLDGKPIRPDSAHKmlvrengvhSLIIEPVTSRDAGIYTCIATNRAGQNSFNLEL 89


                 ..
gi 170295823 595 II 596
Cdd:cd20990   90 VV 91

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

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 40.22 E-value: 3.14e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 515 TIWVSPSP-ILEEGSPVNLTCSSDGIPAPKILWSRQLNNGELQPLSEN-----------TTLTFMSTKRDDSGIYVCEGI 582
Cdd:cd05765    2 ALVNSPTHqTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNhvrgnvvvtniGQLVIYNAQPQDAGLYTCTAR 81


                 ....*..
gi 170295823 583 NEAGISR 589
Cdd:cd05765   82 NSGGLLR 88

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 39.54 E-value: 3.29e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSR---QLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKggsQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 40.20 E-value: 3.37e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 598 VSPKDIQLTvfpSKSVKEGDTVIISCTCGN--VPE-TW------IILKKKAKTGDMVLKSVDG--SYTIRQAQLQDAGIY 666
Cdd:cd05732    1 VQPKITYLE---NQTAVELEQITLTCEAEGdpIPEiTWrratrgISFEEGDLDGRIVVRGHARvsSLTLKDVQLTDAGRY 77

                         90
                 ....*....|....*....
gi 170295823 667 ECESKTEVGSQLRSLTLDV 685
Cdd:cd05732   78 DCEASNRIGGDQQSMYLEV 96

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 39.62 E-value: 3.63e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 331 VVLTCAAIGCDSPSFSWR---TQTDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLCAVT 386
Cdd:cd00096    1 VTLTCSASGNPPPTITWYkngKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 39.87 E-value: 3.83e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRQ----LNNGELQPLSENT--TLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd20972   15 EGSKVRLECRVTGNPTPVVRWFCEgkelQNSPDIQIHQEGDlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 91

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 39.89 E-value: 4.06e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSRQlnNGELQP-----LSENTTLTFMSTKRDDSGIYVCEGINEAGISR 589
Cdd:cd05876    9 RGQSLVLECIAEGLPTPTVKWLRP--SGPLPPdrvkyQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 40.20 E-value: 4.13e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170295823 328 GDSVVLTCAAIGCDSPSFSWRTQTD------SPLNG--VVRNEGAKSTLVLSSVGFEDEHSYLC 383
Cdd:cd05732   16 LEQITLTCEAEGDPIPEITWRRATRgisfeeGDLDGriVVRGHARVSSLTLKDVQLTDAGRYDC 79

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 39.23 E-value: 4.25e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 170295823  45 LTCSTTGCESPLFSWR---TQIDSPLNAKVRTEGSKSVLTMEPVSFENEHSYLCTATCGSG 102
Cdd:cd00096    3 LTCSASGNPPPTITWYkngKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409452 Cd Length: 93 Bit Score: 40.03 E-value: 4.62e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 321 SQVAAQVGDSVVLTCAAIGcDSPSFSWRT----QTDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLCAVTCLQ-RTLEKR 395
Cdd:cd05866    8 SKVELSVGESKFFTCTAIG-EPESIDWYNpqgeKIVSSQRVVVQKEGVRSRLTIYNANIEDAGIYRCQATDAKgQTQEAT 86


                 ....*.
gi 170295823 396 TQVEVY 401
Cdd:cd05866   87 VVLEIY 92

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 39.46 E-value: 5.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 227 TISVHPSTRLQEGGAVTMTCSSEG-LPAPEIFWGR---KLDNEVLQLlsgNATLTLIAMRMEDSGVYVCEGVNLIGRDKA 302
Cdd:cd05754    4 TVEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRvngTLPSRAMDF---NGILTIRNVQLSDAGTYVCTGSNMLDTDEA 80


                 ....
gi 170295823 303 EVEL 306
Cdd:cd05754   81 TATL 84

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 39.44 E-value: 6.33e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 217 LQVYISPRNTTISVhpstrlqeGGAVTMTCSSEGLPAPEIFW---GRKLDNEVLQLLSGNATLTLIAMRMEDSGVYVC 291
Cdd:cd20957    2 LSATIDPPVQTVDF--------GRTAVFNCSVTGNPIHTVLWmkdGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQC 71

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

Pssm-ID: 409518 [Multi-domain] Cd Length: 90 Bit Score: 38.90 E-value: 8.53e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 515 TIWVSPSPILEEGSPVNLTCSSdGIPAPkilWSRQLNNGElqPLSENTTLTFM----------STKRDDSGIYVCEGINE 584
Cdd:cd16843    3 FLSAEPSSVVPLGENVTIRCQG-PPEAV---LFQLYKEGN--SLSQGTVREKEpqnkaefyipHMDRNHAGRYRCRYRSG 76

                         90
                 ....*....|....
gi 170295823 585 AGISRKS--VELII 596
Cdd:cd16843   77 TLWSEPSdpLELVV 90

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

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 8.59e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 611 KSVKEGDTVIISCTCGNVPE---TW---------IILKKKAKTGDMVLKSVdGSYTIRQAQLQDAGIYECESKTEVGS 676
Cdd:cd05765   10 QTVKVGETASFHCDVTGRPQpeiTWekqvpgkenLIMRPNHVRGNVVVTNI-GQLVIYNAQPQDAGLYTCTARNSGGL 86

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 38.72 E-value: 9.07e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823  613 VKEGDTVIISCTC-GNVPETWIILKKKAKTGDMVLKSVDGSYTIRQAQLQ-------DAGIYECESKTEVGSQLRSLTL 683
Cdd:pfam00047   8 VLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLisnvtkeDAGTYTCVVNNPGGSATLSTSL 86

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 39.14 E-value: 9.07e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRQ---LNNGELQ-PLSENTT-LTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd05730   18 GQSVTLACDADGFPEPTMTWTKDgepIESGEEKySFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHL 90

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 39.19 E-value: 9.31e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 526 EGSPVNLTCSSDGIPAPKILWSR-----QLNNGELQPLSE--------NTTLTFMSTKRDDSGIYVCEGINEAGISRKSV 592
Cdd:cd05870   15 ENGAATLSCKAEGEPIPEITWKRasdghTFSEGDKSPDGRievkgqhgESSLHIKDVKLSDSGRYDCEAASRIGGHQKSM 94


                 ....
gi 170295823 593 ELII 596
Cdd:cd05870   95 YLDI 98

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 38.98 E-value: 9.58e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILWSR---QLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELII 596
Cdd:cd04969   13 LAAKGGDVIIECKPKASPKPTISWSKgteLLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Second immunoglobulin (Ig)-like C2-set domain of intercellular cell adhesion molecule 1 (ICAM-1), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of intercellular cell adhesion molecule 1 (ICAM-1; also known as domain of cluster of differentiation (CD) 54) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. ICAM-1 may be involved in organ targeted tumor metastasis. The interaction of ICAM-1 with leukocyte function-associated antigen-1 (LFA-1) plays a part in leukocyte-endothelial cell recognition. This group also contains ICAM-2 which also interacts with LFA-1. Transmigration of immature dendritic cells across resting endothelium is dependent on the interaction of ICAM-2 with, yet unidentified, ligand(s) on the dendritic cells. ICAM-1 has five Ig-like domains and ICAM-2 has two. ICAM-1 may also act as host receptor for viruses and parasites. The structures of this group show that the second Ig domain lacks a D strand and thus belonging to the C2-set of the IgSF

Pssm-ID: 409413 Cd Length: 101 Bit Score: 39.08 E-value: 9.64e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 170295823 129 VGKPVTVKCLAPDIYPVYRLEIDLFKGDQLMNRQEFSSEEMTKsletKSLEVTFTPVI--EDIGKALVCRAKL 199
Cdd:cd05755   16 VGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAP----QPAEATFTVLArrEDHGANFSCLAEL 84

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

Pssm-ID: 409474 Cd Length: 92 Bit Score: 38.92 E-value: 9.84e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 235 RLQEGGAVTMTCSSEGLPAPEIFWGR-------KLDNEVLQL-LSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVEL 306
Cdd:cd05893   11 KIFEGMPVTFTCRVAGNPKPKIYWFKdgkqispKSDHYTIQRdLDGTCSLHTTASTLDDDGNYTIMAANPQGRISCTGRL 90


                 ..
gi 170295823 307 VV 308
Cdd:cd05893   91 MV 92

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 38.54 E-value: 1.03e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  31 PEYKTIAQIGDSMALTCSTTGCESPLFSWRTQIDSPLNAKVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIHV 110
Cdd:cd05731    1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 37.93 E-value: 1.09e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 530 VNLTCSSDGIPAPKILWSR---QLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKdgvQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 39.07 E-value: 1.12e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 227 TISVHPS-TRLQEGGAVTMTCSSEGLPAPEIFW---GRKLDNEVLQLLSGNATL---TLIAMRM-------EDSGVYVCE 292
Cdd:cd07693    2 RIVEHPSdLIVSKGDPATLNCKAEGRPTPTIQWlknGQPLETDKDDPRSHRIVLpsgSLFFLRVvhgrkgrSDEGVYVCV 81


                 ....*.
gi 170295823 293 GVNLIG 298
Cdd:cd07693   82 AHNSLG 87

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 38.77 E-value: 1.15e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 315 VDISPgSQVAAQVGDSVVLTCAAIGcDSPSFSW------RTQTDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLCAVT 386
Cdd:cd04977    3 VKIIP-SYAEISVGESKFFLCKVSG-DAKNINWvspngeKVLTKHGNLKVVNHGSVLSSLTIYNANINDAGIYKCVAT 78

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 38.35 E-value: 1.15e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 527 GSPVNLTCSSDGIPAPKILWsrqLNNGelQPLS-------ENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVEL 594
Cdd:cd05728   14 GSSLRWECKASGNPRPAYRW---LKNG--QPLAsenrievEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAEL 83

Second immunoglobulin (Ig)-like C2-set domain of intercellular cell adhesion molecule 1 (ICAM-1), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of intercellular cell adhesion molecule 1 (ICAM-1; also known as domain of cluster of differentiation (CD) 54) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. ICAM-1 may be involved in organ targeted tumor metastasis. The interaction of ICAM-1 with leukocyte function-associated antigen-1 (LFA-1) plays a part in leukocyte-endothelial cell recognition. This group also contains ICAM-2 which also interacts with LFA-1. Transmigration of immature dendritic cells across resting endothelium is dependent on the interaction of ICAM-2 with, yet unidentified, ligand(s) on the dendritic cells. ICAM-1 has five Ig-like domains and ICAM-2 has two. ICAM-1 may also act as host receptor for viruses and parasites. The structures of this group show that the second Ig domain lacks a D strand and thus belonging to the C2-set of the IgSF

Pssm-ID: 409413 Cd Length: 101 Bit Score: 38.70 E-value: 1.38e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 418 GRPVTVNCTVPNVYPFDHLEIELLKGETTLMKKYFLEEMGIKslETKILETTFIPTIEDTGKSLVCLARL 487
Cdd:cd05755   17 GKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAP--QPAEATFTVLARREDHGANFSCLAEL 84

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.69 E-value: 1.51e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILW---SRQLNNGELQPLSENT-----TLTFMST-----KRDDSGIYVCEGINEAGISR 589
Cdd:cd07693   11 IVSKGDPATLNCKAEGRPTPTIQWlknGQPLETDKDDPRSHRIvlpsgSLFFLRVvhgrkGRSDEGVYVCVAHNSLGEAV 90

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

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 38.31 E-value: 1.71e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 523 ILEEGSPVNLTCSSDGIPAPKILWSrqLNNGELQPL----------SENTTLTFM---STKRDDSGIYVCEGINEAG 586
Cdd:cd20956   12 TLQPGPSVSLKCVASGNPLPQITWT--LDGFPIPESprfrvgdyvtSDGDVVSYVnisSVRVEDGGEYTCTATNDVG 86

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 38.37 E-value: 1.73e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  37 AQIGDSMALTCSTTGCESPLFSWRTQiDSPL---NAKVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIHVDIY 113
Cdd:cd05730   15 ANLGQSVTLACDADGFPEPTMTWTKD-GEPIesgEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVF 93


                 .
gi 170295823 114 S 114
Cdd:cd05730   94 A 94

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 38.20 E-value: 1.77e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 524 LEEGSPVNLTCSSDGIPAPKILWSR-----QLNNGELQPLSENTTLTFMSTK---RDDSGIYVCE 580
Cdd:cd20961    5 VSQGQPVKLNCSVEGMEEPDIQWVKdgavvQNLDQLYIPVSEQHWIGFLSLKsveRSDAGRYWCQ 69

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

Pssm-ID: 409545 Cd Length: 95 Bit Score: 37.91 E-value: 2.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 222 SPRNTTISVHPSTRLQEGGAVTMTCSSEGLPAPEIFWGR-----------KLDNEVLQlLSGnaTLTLIAMRMEDSGVYV 290
Cdd:cd20953    1 APKIPGLSKSQPLTVSSASSIALLCPAQGYPAPSFRWYKfiegttrkqavVLNDRVKQ-VSG--TLIIKDAVVEDSGKYL 77

                         90
                 ....*....|....*...
gi 170295823 291 CEGVNLIGRDKAEVELVV 308
Cdd:cd20953   78 CVVNNSVGGESVETVLTV 95

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

Pssm-ID: 462230 Cd Length: 109 Bit Score: 38.21 E-value: 2.44e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  232 PSTRLQEGGAVTMTC---SSEGLPAPEIFWGRKLDNEVLQLL------------------------SGNATLTLIAMRME 284
Cdd:pfam07686   4 REVTVALGGSVTLPCtysSSMSEASTSVYWYRQPPGKGPTFLiayysngseegvkkgrfsgrgdpsNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*
gi 170295823  285 DSGVYVCEGV-NLIGRDKAEVELVV 308
Cdd:pfam07686  84 DSGTYTCAVIpSGEGVFGKGTRLTV 108

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 37.55 E-value: 2.44e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 504 PLYVNVAPKETTIwvspspileEGSPVNLTCSSDGIPAPKILW---SRQLNNGELQPLSENTTLTFMSTKRD-DSGIYVC 579
Cdd:cd20958    1 PPFIRPMGNLTAV---------AGQTLRLHCPVAGYPISSITWekdGRRLPLNHRQRVFPNGTLVIENVQRSsDEGEYTC 71

                         90
                 ....*....|....*...
gi 170295823 580 EGINEAGIS-RKSVELII 596
Cdd:cd20958   72 TARNQQGQSaSRSVFVKV 89

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

Pssm-ID: 409359 Cd Length: 102 Bit Score: 37.91 E-value: 2.50e-03

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 170295823 651 GSYTIRQAQLQDAGIYECESKTEVGSQLRSLTLDVKG 687
Cdd:cd04970   64 GDLEIVNAQLKHAGRYTCTAQTVVDSDSASATLVVRG 100

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 37.44 E-value: 3.22e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823 236 LQEGGAVTMTCSSEGLPAPEIFW---GRKLDNEVLQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd04969   14 AAKGGDVIIECKPKASPKPTISWskgTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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

Pssm-ID: 465231 Cd Length: 63 Bit Score: 36.46 E-value: 3.28e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823  530 VNLTCSSDGipaPKILWsrqLNNGELQPLSENTTLTFMSTKRDDSGIYVCEGINEA 585
Cdd:pfam16680   4 VLLTCNSSS---KSITW---LKDGKGIKSTNTKTLDLGKFSEDPRGLYQCQGEKKK 53

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

Pssm-ID: 409418 Cd Length: 102 Bit Score: 37.79 E-value: 3.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 223 PRNTTISVHPSTrLQEGGAVTMTC-SSEGLPAPEIFWgRKLDNEVLQLLSGNA-----------TLTLIAMRMEDSGVYV 290
Cdd:cd05761    4 PEKPVITGFTSP-VVEGDEITLTCtTSGSKPAADIRW-FKNDKELKGVKEVQEsgagktftvtsTLRFRVDRDDDGVAVI 81


                 ..
gi 170295823 291 CE 292
Cdd:cd05761   82 CR 83

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

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 37.14 E-value: 3.50e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRQLnnGELQP----LSENTTLTFMSTKRDDSGIYVCEGINEAGISRKSVELIIQ 597
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKWRKVD--GSPSSqweiTTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 37.37 E-value: 3.53e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170295823 312 PFIVDiSPGSQVAAQVGDSVVLTCAAIGCDSPSFSWrTQTDSPLNGvvRNEGA---KSTLVLSSVGFEDEHSYLC 383
Cdd:cd20978    1 PKFIQ-KPEKNVVVKGGQDVTLPCQVTGVPQPKITW-LHNGKPLQG--PMERAtveDGTLTIINVQPEDTGYYGC 71

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 36.70 E-value: 3.65e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 170295823 328 GDSVVLTCAAIGCDSPSFSWRTQ---TDSPLNGVVRNEGAKSTLVLSSVGFEDEHSYLC 383
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNwghVPDSARVSITSEGGYGTLTIRDVKESDQGAYTC 59

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

Pssm-ID: 409579 Cd Length: 94 Bit Score: 37.16 E-value: 3.68e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 170295823 407 PVIKMSGPLVHGRPVTVNCTVPNVYPFDHLEIELLkGETTLMKKYFLEEMGIKSLETKILETTFIPTIEDTGKSLVC 483
Cdd:cd20987    1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWL-GAALTPLPPVLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTC 76

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

Pssm-ID: 409473 Cd Length: 92 Bit Score: 37.06 E-value: 4.19e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170295823 233 STRLQEGGAVTMTCSSEGLPAPEIFWgrKLDNEVLQLL----------SGNATLTLIAMRMEDSGVYVCEGVNLIG 298
Cdd:cd05892    9 NKKVLEGDPVRLECQISAIPPPQIFW--KKNNEMLQYNtdrislyqdnCGRICLLIQNANKKDAGWYTVSAVNEAG 82

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 36.88 E-value: 5.49e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 598 VSPKDIQLTvfpSKSVKEGDTVIISCTCGN--VPE-TWiilkKKAKTGDMVL---KSVDG-----------SYTIRQAQL 660
Cdd:cd05870    1 VQPHIIQLK---NETTVENGAATLSCKAEGepIPEiTW----KRASDGHTFSegdKSPDGrievkgqhgesSLHIKDVKL 73

                         90       100
                 ....*....|....*....|....*
gi 170295823 661 QDAGIYECESKTEVGSQLRSLTLDV 685
Cdd:cd05870   74 SDSGRYDCEAASRIGGHQKSMYLDI 98

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

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 36.72 E-value: 5.53e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823 237 QEGGAVTMTC-SSEGLPAPEIFW-------GRKLDNEV-LQLLSGNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELV 307
Cdd:cd05750   12 QEGSKLVLKCeATSENPSPRYRWfkdgkelNRKRPKNIkIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNVT 91


                 .
gi 170295823 308 V 308
Cdd:cd05750   92 V 92

Immunoglobulin-like domain of Mucosal addressin cell-adhesion molecule (MAdCAM-1); member of the I-set of IgSF domains; The members here include the immunoglobulin-like domain of Mucosal addressin cell-adhesion molecule (MAdCAM-1). MadCAM-1 is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), L-selectin, and VLA-4 (alpha4beta1) on myeloid cells to direct leukocytes into mucosal and inflamed tissues. MadCAM-1 is expressed primarily on HEV of Peyer's patches and on venules in small intestinal lamina propria, on the marginal sinus of the spleen, and on HEV of embryonic lymph nodes. It is a member of the immunoglobulin superfamily (IgSF), which is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of MAdCAM-1 is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409535 Cd Length: 88 Bit Score: 36.64 E-value: 6.66e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  31 PEYKTIAQIGDSMALTCSTTGCE-SPLFSWRTqIDSPLNAkVRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIH 109
Cdd:cd20942    7 PEPVVAVALGASRQLTCRLACADrGASVQWRG-LDTSLGA-VQSDTGRSVLTVRNASLSAAGTRVCVGSCGGRTFQHTVQ 84


                 ....
gi 170295823 110 VDIY 113
Cdd:cd20942   85 LLVY 88

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

Pssm-ID: 409462 Cd Length: 125 Bit Score: 37.21 E-value: 6.72e-03

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 170295823 272 GNATLTLIAMRMEDSGVYVCEGVNLIGRDKAEVELVV 308
Cdd:cd05878   84 SDATLEVQSLRASDSGLYRCEVMHGIEDSQDTVELVV 120

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 36.73 E-value: 7.20e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170295823  40 GDSMALTCSTTGCESPLFSWRTQIDSPLNAK--------VRTEGSKSVLTMEPVSFENEHSYLCTATCGSGKLERSIHVD 111
Cdd:cd05732   16 LEQITLTCEAEGDPIPEITWRRATRGISFEEgdldgrivVRGHARVSSLTLKDVQLTDAGRYDCEASNRIGGDQQSMYLE 95


                 .
gi 170295823 112 I 112
Cdd:cd05732   96 V 96

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 35.85 E-value: 8.37e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170295823 527 GSPVNLTCSSDGIPAPKILWSRQlnNGELQPLSE-----NTTLTFMSTKRDDSGIYVCEGINEAGISR 589
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKL--GGELPKGRTkfenfNKTLKIENVSEADSGEYQCTASNTMGSAR 75