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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106    280 WVREGDTVQLLCRGDGSPSPEYTLFR------LQDEQEEVLNVNLEGNLTLEGVTRGQSGTYGCRVEDydaaDDVQLSKT 353
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATN----SSGSASSG 80

                   ....*
gi 31543106    354 LELRV 358
Cdd:smart00410  81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106   464 REGDEVTLICSARGHPDPKLSWSQLGGSPAEPIPGRQGWVSSSLTLKVTSALSRD-GI-SCEASN 526
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDaGTyTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106    280 WVREGDTVQLLCRGDGSPSPEYTLFR------LQDEQEEVLNVNLEGNLTLEGVTRGQSGTYGCRVEDydaaDDVQLSKT 353
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATN----SSGSASSG 80

                   ....*
gi 31543106    354 LELRV 358
Cdd:smart00410  81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106   464 REGDEVTLICSARGHPDPKLSWSQLGGSPAEPIPGRQGWVSSSLTLKVTSALSRD-GI-SCEASN 526
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDaGTyTCVASN 78

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31543106 469 VTLICSARGHPDPKLSWSQLGGSPAEPIPGRQGWVSSSLTLKVTSALSRDG--ISCEASNPHGNKRH 533
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSgtYTCVASNSAGGSAS 67

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31543106 380 AVVNCSVHGLPTPALRWTKDSTPLGDGPM-----------LSLSSITFDSNGTYVCEAS 427
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrrselgngtLTISNVTLEDSGTYTCVAS 59

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106    370 KVLSLPLNSSAVVNCSVHGLPTPALRWTKDS------------TPLGDGPMLSLSSITFDSNGTYVCEASLPTVpvlSRT 437
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgkllaesgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSG---SAS 78

                   ....*..
gi 31543106    438 QNFTLLV 444
Cdd:smart00410  79 SGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106     38 PPLVEVMRGKSVILDCTPTGTHDHYMlEWFltdRSGARPRLASAEMQGSElqvtmhdtrgrsppyqLDSQGRLVLAEAQV 117
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEV-TWY---KQGGKLLAESGRFSVSR----------------SGSTSTLTISNVTP 60

                           90
                   ....*....|.
gi 31543106    118 GDERDYVCVVR 128
Cdd:smart00410  61 EDSGTYTCAAT 71

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106    280 WVREGDTVQLLCRGDGSPSPEYTLFR------LQDEQEEVLNVNLEGNLTLEGVTRGQSGTYGCRVEDydaaDDVQLSKT 353
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATN----SSGSASSG 80

                   ....*
gi 31543106    354 LELRV 358
Cdd:smart00410  81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106   464 REGDEVTLICSARGHPDPKLSWSQLGGSPAEPIPGRQGWVSSSLTLKVTSALSRD-GI-SCEASN 526
Cdd:pfam13927  14 REGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDaGTyTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106   271 VGSPSTPAgwVREGDTVQLLCRGDGSPSPEYTLFRLQDEQEEV-----LNVNLEGNLTLEGVTRGQSGTYGCRVE 340
Cdd:pfam13927   5 TVSPSSVT--VREGETVTLTCEATGSPPPTITWYKNGEPISSGstrsrSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106    460 DGSWREGDEVTLICSARGHPDPKLSWSQLGGSPAEPIPGRQG-WVSSSLTLKVTSALSRD-GI-SCEASNPHGNK 531
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVsRSGSTSTLTISNVTPEDsGTyTCAATNSSGSA 77

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31543106 380 AVVNCSVHGLPTPALRWTKDSTPLGDGPM-----------LSLSSITFDSNGTYVCEAS 427
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrrselgngtLTISNVTLEDSGTYTCVAS 59

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31543106 466 GDEVTLICSARGHPDPKLSWSQLGGspaEPIPGRQGWVSSSLTLKVTSALSRDG--ISCEASNPHGNKRHVFH 536
Cdd:cd05731  10 GGVLLLECIAEGLPTPDIRWIKLGG---ELPKGRTKFENFNKTLKIENVSEADSgeYQCTASNTMGSARHTIS 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31543106   281 VREGDTVQLLCRGDGSPSPEYTLFRlqdeQEEVLNVNleGNLTLEGVTRGQSGTYGCRvedYDAADDVQLSKTLELRV 358
Cdd:pfam13895  11 VTEGEPVTLTCSAPGNPPPSYTWYK----DGSAISSS--PNFFTLSVSAEDSGTYTCV---ARNGRGGKVSNPVELTV 79

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31543106 465 EGDEVTLICSARGHPDPKLSW-------SQLGGSPAEPIPGRQGWVSSSLTLKVTSALSRDGISCEASNPHG 529
Cdd:cd05732  15 ELEQITLTCEAEGDPIPEITWrratrgiSFEEGDLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEASNRIG 86

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106 465 EGDEVTLICSARGHPDPKLSWSQlGGSPAEpiPGRQGWVSSSLTLKVTS-ALSRDG-ISCEASNPHGNKRHVFHF 537
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTK-GGSQLS--VDRRHLVLSSGTLRISRvALHDQGqYECQAVNIVGSQRTVAQL 72

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106 466 GDEVTLICSARGHPDPKLSWSQLggspAEPIPGRQGWVSSSLTLKVTSALSRD-GI-SCEASNPHGNKRH 533
Cdd:cd05851  16 GQNVTLECFALGNPVPVIRWRKI----LEPMPATAEISMSGAVLKIFNIQPEDeGTyECEAENIKGKDKH 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106    370 KVLSLPLNSSAVVNCSVHGLPTPALRWTKDS------------TPLGDGPMLSLSSITFDSNGTYVCEASLPTVpvlSRT 437
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgkllaesgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSG---SAS 78

                   ....*..
gi 31543106    438 QNFTLLV 444
Cdd:smart00410  79 SGTTLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106   464 REGDEVTLICSARGHPDPKLSWSQlggsPAEPIPGRQgwvsSSLTLKVTSALSrdGI-SCEASNPHGNKR 532
Cdd:pfam13895  12 TEGEPVTLTCSAPGNPPPSYTWYK----DGSAISSSP----NFFTLSVSAEDS--GTyTCVARNGRGGKV 71

First immunoglobulin (Ig)-like domain in neogenin, 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 in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31543106 379 SAVVNCSVHGLPTPALRWTKDST-----------PLGDGPML--SLSSITFDS--NGTYVCEASLPTV-PVLSRT 437
Cdd:cd05722  18 PVVLNCSAESDPPPKIEWKKDGVllnlvsderrqQLPNGSLLitSVVHSKHNKpdEGFYQCVAQNESLgSIVSRT 92

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106 379 SAVVNCSVHGLPTPALRWTK---DSTP--------LGDGPMLSLSSITFDSNGTYVCEAS 427
Cdd:cd05736  17 EASLRCHAEGIPLPRVQWLKngmDINPklskqltlIANGSELHISNVRYEDTGAYTCIAK 76

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 31543106 376 LNSSAVVNCSVHGLPTPALRWTKD--STPLG-----DGPMLSLSSITFDSNGTYVCEA 426
Cdd:cd05725  11 VDDSAEFQCEVGGDPVPTVRWRKEdgELPKGryeilDDHSLKIRKVTAGDMGSYTCVA 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31543106 281 VREGDTVQLLCRGDGSPSPEYTLF----RLQDEQEevlNVNLE-GNLTLEGVTRGQSGTYGCRVEDY 342
Cdd:cd20978  13 VKGGQDVTLPCQVTGVPQPKITWLhngkPLQGPME---RATVEdGTLTIINVQPEDTGYYGCVATNE 76

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31543106   361 LDPLELSEGKVLSLplnssavvNCSVHGLPTPALRWTKDSTPL-----------GDGPMLSLSSITFDSNGTYVCEAS 427
Cdd:pfam07679   7 PKDVEVQEGESARF--------TCTVTGTPDPEVSWFKDGQPLrssdrfkvtyeGGTYTLTISNVQPDDSGKYTCVAT 76

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543106 152 VSPNKGTLSVMEDSAQE----IATCNSRNGNPAPKITWYRNGQRLEVPVEMNPEGYMTSRTVreasgllslTSTLYLRLR 227
Cdd:cd05761   2 GVPEKPVITGFTSPVVEgdeiTLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTV---------TSTLRFRVD 72

                        90
                ....*....|....*...
gi 31543106 228 KDDRDASFHCAA-HYSLP 244
Cdd:cd05761  73 RDDDGVAVICRVdHESLT 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.

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gi 31543106 466 GDEVTLICSARGHPDPKLSWSqLGGSPAEPIPG-RQG-WVSSSLT----LKVTSALSRDG--ISCEASNPHGNKRH 533
Cdd:cd20956  16 GPSVSLKCVASGNPLPQITWT-LDGFPIPESPRfRVGdYVTSDGDvvsyVNISSVRVEDGgeYTCTATNDVGSVSH 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.

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gi 31543106 378 SSAVVNCSVHGLPTPALRWTKDSTPL----------GDGPMLSLSSITFDSNGTYVCEAS 427
Cdd:cd20970  18 ENATFMCRAEGSPEPEISWTRNGNLIiefntryivrENGTTLTIRNIRRSDMGIYLCIAS 77