Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1358101711 235 PPTITESKSN-EATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAAN 311
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711  55 TDNITVRQGDTAILRCVVED-KNSKVAWLNRSG-IIFAGHDKWSLDPRVELEKRHALEYSLRIQKVDVYDEGSYTCSVQT 132
Cdd:cd05717     3 TQDVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYT 82

                          90
                  ....*....|...
gi 1358101711 133 QhEPKTSQVYLIV 145
Cdd:cd05717    83 D-PVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1358101711 235 PPTITESKSN-EATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAAN 311
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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 1358101711  241 SKSNEATTGRQASLKCEASAVPAPDFEWYRDDTR-INSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTNAS 319
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ...
gi 1358101711  320 LVL 322
Cdd:smart00410  81 TTL 83

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 1358101711  55 TDNITVRQGDTAILRCVVED-KNSKVAWLNRSG-IIFAGHDKWSLDPRVELEKRHALEYSLRIQKVDVYDEGSYTCSVQT 132
Cdd:cd05717     3 TQDVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYT 82

                          90
                  ....*....|...
gi 1358101711 133 QhEPKTSQVYLIV 145
Cdd:cd05717    83 D-PVSTKKVTVTV 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711  155 SSDVTVNEGSNVTLVCMANGRPEPVITWRH-----LTPLGREFEGEEEYLEIL---GITREQSGKYECKAANEVSSADvK 226
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqggklLAESGRFSVSRSGSTSTLtisNVTPEDSGTYTCAATNSSGSAS-S 79

                   ....*.
gi 1358101711  227 QVKVTV 232
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711  51 FNRGTDNITVRQGDTAILRCVVE-DKNSKVAWL-NRSGIifaghdkwSLDPRVELEKRHAlEYSLRIQKVDVYDEGSYTC 128
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFkDGQPL--------RSSDRFKVTYEGG-TYTLTISNVQPDDSGKYTC 73

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1358101711 235 PPTITESKSN-EATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAAN 311
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 252 ASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTNASLV 321
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711  241 SKSNEATTGRQASLKCEASAVPAPDFEWYRDDTR-INSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTNAS 319
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ...
gi 1358101711  320 LVL 322
Cdd:smart00410  81 TTL 83

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 1358101711  55 TDNITVRQGDTAILRCVVED-KNSKVAWLNRSG-IIFAGHDKWSLDPRVELEKRHALEYSLRIQKVDVYDEGSYTCSVQT 132
Cdd:cd05717     3 TQDVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYT 82

                          90
                  ....*....|...
gi 1358101711 133 QhEPKTSQVYLIV 145
Cdd:cd05717    83 D-PVSTKKVTVTV 94

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 149 PKISNISSDVTVNEGSNVTLVCMANGRPEPVITWRH----LTPLGREFEGEEEYLE---ILGITREQSGKYECKAANEVS 221
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKdgqpLRSSDRFKVTYEGGTYtltISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|.
gi 1358101711 222 SADVKqVKVTV 232
Cdd:pfam07679  81 EAEAS-AELTV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 144 IVQVPPKisniSSDVTVNEGSNVTLVCMANGRPEPVITWRH------LTPLGREFEGEEEYLEILGITREQSGKYECKAA 217
Cdd:cd20970     2 VISTPQP----SFTVTAREGENATFMCRAEGSPEPEISWTRngnliiEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIAS 77

                          90
                  ....*....|....*
gi 1358101711 218 NEVSSADVKQVKVTV 232
Cdd:cd20970    78 NGVPGSVEKRITLQV 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 236 PTITESKSNEATTGRQASLKCEASAVPAPDFEWYRDDTRINSANG-----LEIKSTEGQSSLTVTNVTEEHYGNYTCVAA 310
Cdd:cd05732     3 PKITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEGdldgrIVVRGHARVSSLTLKDVQLTDAGRYDCEAS 82

                          90
                  ....*....|..
gi 1358101711 311 NKLGVTNASLVL 322
Cdd:cd05732    83 NRIGGDQQSMYL 94

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 235 PPTIT--ESKSNE-ATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGlEIKSTEGQSSLTVTNVTEEHYGNYTCVAAN 311
Cdd:cd05730     1 PPTIRarQSEVNAtANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEE-KYSFNEDGSEMTILDVDKLDEAEYTCIAEN 79

                          90
                  ....*....|.
gi 1358101711 312 KLGVTNASLVL 322
Cdd:cd05730    80 KAGEQEAEIHL 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 236 PTITESKSNEATT---GRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQsSLTVTNVTEEHYGNYTCVAANK 312
Cdd:cd20970     1 PVISTPQPSFTVTareGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT-TLTIRNIRRSDMGIYLCIASNG 79

                  ..
gi 1358101711 313 LG 314
Cdd:cd20970    80 VP 81

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1358101711 249 GRQASLKCEASAVPAPDFEWYRDDTRINSANglEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTNAS 319
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPE--IGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINAT 87

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 236 PTITE-SKSNEATTGRQ-ASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTN---VTEEHYGNYTCVAA 310
Cdd:cd05733     1 PTITEqSPKDYIVDPRDnITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRRSGTLVIDNhngGPEDYQGEYQCYAS 80

                  ....
gi 1358101711 311 NKLG 314
Cdd:cd05733    81 NELG 84

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 236 PTITESKSNeATTGRQASLKCEASAVPAPDFEWYRDDTRINSangleikstegQSSLTVTNVTEEHYGNYTCVAANKLGV 315
Cdd:pfam13895   2 PVLTPSPTV-VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS-----------SPNFFTLSVSAEDSGTYTCVARNGRGG 69

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 148 PPKISNISSDVTVNEGSNVTLVCMANGRPEPVITWRHL---TPLGREFEGEEEYLEILGITREQSGKYECKAANeVSSAD 224
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKIlepMPATAEISMSGAVLKIFNIQPEDEGTYECEAEN-IKGKD 79

                  ....*...
gi 1358101711 225 VKQVKVTV 232
Cdd:cd05851    80 KHQARVYV 87

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1358101711 249 GRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTN--ASLVL 322
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEdiSSLFV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. 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 1358101711 245 EATTGRQA-SLKCEASAVPAPDFEWYRddtrinsaNGLEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKL 313
Cdd:cd05863    14 EATAGDELvKLPVKVAAYPPPEFQWYK--------DGKLISGKHSPHSLQIKDVTEASAGTYTLVLWNSA 75

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1358101711 148 PPKISNISSDVTVNEGSNVTLVCMANGRPEPVITW----RHLTPLGREFEGEEEYLEILGITREQSGKYECKAANE 219
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWlhngKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNE 76

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1358101711 254 LKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEGQS-SLTVTNVTEEHYGNYTCVAANKLGVTNAS 319
Cdd:cd05729    24 LECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYGSINHT 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 1358101711 235 PPTITESKSNEATT-GRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIK---STEGQ--SSLTVTNVTEEHYGNYTCV 308
Cdd:cd20956     1 APVLLETFSEQTLQpGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGdyvTSDGDvvSYVNISSVRVEDGGEYTCT 80

                  ....*.
gi 1358101711 309 AANKLG 314
Cdd:cd20956    81 ATNDVG 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1358101711 254 LKCEASAVPAPDFEWYRddtrinsANGLEIKSTEG----QSSLTVTNVTEEHYGNYTCVAANKLG 314
Cdd:cd05731    15 LECIAEGLPTPDIRWIK-------LGGELPKGRTKfenfNKTLKIENVSEADSGEYQCTASNTMG 72

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 156 SDVTVNEGSNVTLVCMANGRPEPVITWR------HLTPLGREFEGEEEYLEILGITREQSGKYECKAANE 219
Cdd:cd04978     7 PSLVLSPGETGELICEAEGNPQPTITWRlngvpiEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1358101711 242 KSNEATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKSTEgqssLTVTNVTEEHYGNYTCVAANKLGVTNAS 319
Cdd:cd05728     7 SDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD----LRITKLSLSDSGMYQCVAENKHGTIYAS 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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1358101711 254 LKCEASAVPAPDFEWYRDDTRINSANglEIKSTEGQSSLTVTNVTEEHYGNYTCVAANKLGVTNASLVL 322
Cdd:cd20952    19 LNCQATGEPVPTISWLKDGVPLLGKD--ERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 242 KSNEATTGRQASLKCEASAVPAPDFEWYRDDTRINSANGLEIKStegQSSLTVTNVTEEHYGNYTCVAANKLGVTNASLV 321
Cdd:cd04969    10 KKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP---DGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGS 86

                  .
gi 1358101711 322 L 322
Cdd:cd04969    87 L 87

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1358101711 155 SSDVTVNEGSNVTLVCMANGRPEPVITWRH-----LTPLGREFEGEEEYLEILGITREQSGKYECKAANEVSSADVKQV 228
Cdd:cd20952     6 PQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvplLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 149 PKI-SNISSDVTVNEGSNVTLVCMANGRPEPVITWRHL---TPLGREFEGEEEYLEILGITREQSGKYECKAANeVSSAD 224
Cdd:cd04968     1 PSIkVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVdgsPSSQWEITTSEPVLEIPNVQFEDEGTYECEAEN-SRGKD 79

                  ....*...
gi 1358101711 225 VKQVKVTV 232
Cdd:cd04968    80 TVQGRIIV 87

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1358101711 235 PPTITESksneatTGRQASLKCEASAVPAPDFEWyrddtRINsANGLEIKSTEGQ-----SSLTVTNVTEEHYGNYTCVA 309
Cdd:cd04978     6 PPSLVLS------PGETGELICEAEGNPQPTITW-----RLN-GVPIEPAPEDMRrtvdgRTLIFSNLQPNDTAVYQCNA 73

                          90
                  ....*....|...
gi 1358101711 310 ANKLG--VTNASL 320
Cdd:cd04978    74 SNVHGylLANAFL 86