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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 665410190   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 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 665410190   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 665410190   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 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 665410190    80 PRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILtvgsytytSDQRFQATHhqDTEDWTLQIKWAQKRDAGMYECQI 159
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*.
gi 665410190   160 STqPVRSYFVRLNVVV 175
Cdd:smart00410  71 TN-SSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190   73 PYFDpSTPRNVTALMGKSAYLSCRVRNLANKTVSWiRHRDIHIltvgsytyTSDQRFQAthHQDTEDWTLQIKWAQKRDA 152
Cdd:pfam07679   1 PKFT-QKPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPL--------RSSDRFKV--TYEGGTYTLTISNVQPDDS 68

                  ....*.
gi 665410190  153 GMYECQ 158
Cdd:pfam07679  69 GKYTCV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 665410190   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 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 665410190    80 PRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILtvgsytytSDQRFQATHhqDTEDWTLQIKWAQKRDAGMYECQI 159
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*.
gi 665410190   160 STqPVRSYFVRLNVVV 175
Cdd:smart00410  71 TN-SSGSASSGTTLTV 85

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  79 TPRNVTALMGKSAYLSCRVRNLANKT-VSWIRHRD----IHILTVGS----YTYTSDQRFQATHhQDTEDWTLQIKWAQK 149
Cdd:cd00099    4 SPRSLSVQEGESVTLSCEVSSSFSSTyIYWYRQKPgqgpEFLIYLSSskgkTKGGVPGRFSGSR-DGTSSFSLTISNLQP 82

                         90
                 ....*....|....
gi 665410190 150 RDAGMYECQISTQP 163
Cdd:cd00099   83 EDSGTYYCAVSESG 96

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190   79 TPRNVTALMGKSAYLSCRVRNLANKT---VSWIRHRDIHILTVGSYTYTSDQ-------RFQATHHQDTEDWTLQIKWAQ 148
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKGPTFLIAYYSNGSeegvkkgRFSGRGDPSNGDGSLTIQNLT 81

                          90       100
                  ....*....|....*....|....*...
gi 665410190  149 KRDAGMYECQISTQPVRSYF--VRLNVV 174
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEGVFGkgTRLTVL 109

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665410190 194 INLTCTVKFSPEPpaYIFWYHHEEVINYDSSRGGVSVitekgdVTTSFLLIQNADLADSGKYSCAPSNADVASVRVHV 271
Cdd:cd00096    1 VTLTCSASGNPPP--TITWYKNGKPLPPSSRDSRRSE------LGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  73 PYFDPSTPRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILTVGSYTYTSDQRFQATHHQDTEDW-TLQIKWAQKRD 151
Cdd:cd04974    1 PILQAGLPANQTVVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKYGPDGLPYVTVLKVAGVNTTGEEnTLTISNVTFDD 80

                 ....*.
gi 665410190 152 AGMYEC 157
Cdd:cd04974   81 AGEYIC 86

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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, Necl-2, and Necl-3 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 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  81 RNVTALMGKSAYLSCRVRNLANKTVSWIRHRDiHILTVGSYTYTSDQRFQATHHQDTE------DWTLQikwaqkrDAGM 154
Cdd:cd05717    4 QDVTVVEGETLTLKCQVSLRDDSSLQWLNPNG-QTIYFNDKRALRDSRYQLLNHSASElsisvsNVTLS-------DEGV 75

                         90
                 ....*....|....*....
gi 665410190 155 YECQISTQPVRSYFVRLNV 173
Cdd:cd05717   76 YTCLHYTDPVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190   78 STPRNVTALMGKSAYLSCRVRNLANKTVSWIRHrdihiltvGSYTYTSDQRFQATHHQDTedwTLQIKWAQKRDAGMYEC 157
Cdd:pfam13927   6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKN--------GEPISSGSTRSRSLSGSNS---TLTISNVTRSDAGTYTC 74

                  ...
gi 665410190  158 QIS 160
Cdd:pfam13927  75 VAS 77

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665410190  191 GSTINLTCTVKFSpEPPAYIFWYHheeviNYDSSRGGVSVITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:pfam00047  11 GDSATLTCSASTG-SPGPDVTWSK-----EGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPG 77

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665410190 188 VDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSsrggvsvitEKGDVTTSFLLIQNADLADSGKYSCAPSN 261
Cdd:cd20978   13 VKGGQDVTLPCQVTGVPQP--KITWLHNGKPLQGPM---------ERATVEDGTLTIINVQPEDTGYYGCVATN 75

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  76 DPSTPRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILTVGSYTYTSDQRfqathhqdtedwTLQIKWAQKRDAGMY 155
Cdd:cd20970    5 TPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT------------TLTIRNIRRSDMGIY 72

                 ....*
gi 665410190 156 ECQIS 160
Cdd:cd20970   73 LCIAS 77

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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 has 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  82 NVTALMGKSAYLSCRVRNLANKTVSWiRHRDIHILTVGSYTYTSDQRFQATHHQDTEdWTLQIKWAQKRDAGMYECQIST 161
Cdd:cd05882    6 DETVAVGGTVTLKCGVKEHDNSSLQW-SNTAQQTLYFGEKRALRDNRIQLVKSTPTE-LIISISNVQLSDEGEYTCSIFT 83

                 ....*
gi 665410190 162 QPVRS 166
Cdd:cd05882   84 MPVRT 88

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190 178 ATILGG-PDL-HVDKGSTINLTCTVkfSPEPPAYIFWYHHEEVINYdSSRGGVSVitEKGdvTTSFLLIQNADLADSGKY 255
Cdd:cd05737    1 ARVLGGlPDVvTIMEGKTLNLTCNV--WGDPPPEVSWLKNDQALAF-LDHCNLKV--EAG--RTVYFTINGVSSEDSGKY 73

                 .
gi 665410190 256 S 256
Cdd:cd05737   74 G 74

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  79 TPRNVTALMGKSAYLSCRVRNLANKT--VSWIRHRD-------IHILTVGSYTYTSDQ---RFQATHHQDTEDWTLQIKW 146
Cdd:cd04982    4 PQLSITREESKSVTISCKVSGIDFSTtyIHWYRQKPgqalerlLYVSSTSAVRKDSGKtknKFEARKDVGKSTSTLTITN 83

                         90
                 ....*....|.
gi 665410190 147 AQKRDAGMYEC 157
Cdd:cd04982   84 LEKEDSATYYC 94

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190 180 ILGG-PDL-HVDKGSTINLTCTVKFSPEPPayIFWYHHEEVINYDSSrggVSVITEKGDVTTsfLLIQNADLADSGKYSC 257
Cdd:cd05891    3 VIGGlPDVvTIMEGKTLNLTCTVFGNPDPE--VIWFKNDQDIELSEH---YSVKLEQGKYAS--LTIKGVTSEDSGKYSI 75

                 ....
gi 665410190 258 APSN 261
Cdd:cd05891   76 NVKN 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  73 PYFDPSTPRNVTALMGKSAYLSCRVRNLANKTVSWIrHRDIHIltvgsytytSDQRFQATHHQDtedwTLQIKWAQKRDA 152
Cdd:cd20978    1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWL-HNGKPL---------QGPMERATVEDG----TLTIINVQPEDT 66

                 ....*
gi 665410190 153 GMYEC 157
Cdd:cd20978   67 GYYGC 71

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665410190  78 STPRNVTALMGKSAYLSCRVRNLANKTVSWIRhrDIHILTVgsytytSDQRFQAThhqdtEDWTLQIKWAQKRDAGMYEC 157
Cdd:cd20952    4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLK--DGVPLLG------KDERITTL-----ENGSLQIKGAEKSDTGEYTC 70

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.

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gi 665410190  78 STPRNVTALMGKSAYLSCRVRNLANKTVSWirHRDIHILTVGSYtytsdqrfqathhQDTEDWTLQIKWAQKRDAGMYEC 157
Cdd:cd05725    2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRW--RKEDGELPKGRY-------------EILDDHSLKIRKVTAGDMGSYTC 66

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gi 665410190 158 Q 158
Cdd:cd05725   67 V 67

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.

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gi 665410190 188 VDKGSTINLTCTVKFSPePPAyIFWYHHEEVINYDSSRGGVSVITEkGDVTTSFLLIQnadlaDSGKYSCAPSNA---DV 264
Cdd:cd20969   14 VDEGHTVQFVCRADGDP-PPA-ILWLSPRKHLVSAKSNGRLTVFPD-GTLEVRYAQVQ-----DNGTYLCIAANAggnDS 85

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gi 665410190 265 ASVRVHV 271
Cdd:cd20969   86 MPAHLHV 92

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

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gi 665410190  77 PSTPRNVTALMGKSAYLSCRVRN-LANKTVSW-IRHRDIhiltvgSYTYTSDQRFQATHHQDTE--DWTLQIKWAQKRDA 152
Cdd:cd20946    3 PSSQQVVTVVENQEVILSCKTPKkTSSPRVEWkKLQRDV------TFVVFQNNKIQGDYKGRAEilGTNITIKNVTRSDS 76

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gi 665410190 153 GMYECQIS 160
Cdd:cd20946   77 GKYRCEVS 84