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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903   223 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 302
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823903   303 SV 304
Cdd:smart00410  84 TV 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 578823903   223 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 302
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823903   303 SV 304
Cdd:smart00410  84 TV 85

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 578823903 226 VTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVRE 297
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLTISNVTLE-DSGTYTCVASNSAGGSA 66

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578823903  38 ENVTLHCgNISGLRG--QVTWYRN--NSEPVFLLSSNSSLRP----AEPRF--SLVDAT--SLHIESLSLGDEGIYTCQ 104
Cdd:cd00099   14 ESVTLSC-EVSSSFSstYIYWYRQkpGQGPEFLIYLSSSKGKtkggVPGRFsgSRDGTSsfSLTISNLQPEDSGTYYCA 91

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903   223 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 302
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823903   303 SV 304
Cdd:smart00410  84 TV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903  210 PSLLSEPMKT-CFTGGNVTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICR 288
Cdd:pfam13927   2 PVITVSPSSVtVREGETVTLTCEATG-SPPPTITWYKN----GEPISSGSTRSRSLSGSNSTLTISNVTRS-DAGTYTCV 75

                  .
gi 578823903  289 A 289
Cdd:pfam13927  76 A 76

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 578823903 223 GGNVTLTCQVSGaYPPAKILWLRNLTQPEVIIQpssRHLITQDGQnsTLTIHNCsQDLDEGYYICRADSPV-GVREMEIW 301
Cdd:cd20970   17 GENATFMCRAEG-SPEPEISWTRNGNLIIEFNT---RYIVRENGT--TLTIRNI-RRSDMGIYLCIASNGVpGSVEKRIT 89

                 ...
gi 578823903 302 LSV 304
Cdd:cd20970   90 LQV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903    31 VVIGEVHENVTLHCGNISGLRGQVTWYRNNSEPVFllssnsslrpAEPRFSLV---DATSLHIESLSLGDEGIYTCQ-EI 106
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA----------ESGRFSVSrsgSTSTLTISNVTPEDSGTYTCAaTN 72

                           90
                   ....*....|...
gi 578823903   107 LNVTQWFQVWLQV 119
Cdd:smart00410  73 SSGSASSGTTLTV 85

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 578823903   29 EAVVIGEVHENVTLHC---GNISGLRGQVTWYR----NNSEPVFLLSSNSSLRPAEP-RFSLVDAT-----SLHIESLSL 95
Cdd:pfam07686   3 PREVTVALGGSVTLPCtysSSMSEASTSVYWYRqppgKGPTFLIAYYSNGSEEGVKKgRFSGRGDPsngdgSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*.
gi 578823903   96 GDEGIYTCQEILNVTQWFQ--VWLQV 119
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGkgTRLTV 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 218 KTCFTGGNVTLTCQVSGAyPPAKILWLRNLTQpeviIQPSSRH-LITQDGQNSTLTIHNCSQdLDEGYYICRADSPVGVR 296
Cdd:cd05744   10 LEVQEGRLCRFDCKVSGL-PTPDLFWQLNGKP----VRPDSAHkMLVRENGRHSLIIEPVTK-RDAGIYTCIARNRAGEN 83

                 ....*...
gi 578823903 297 EMEIWLSV 304
Cdd:cd05744   84 SFNAELVV 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 216 PMK--TCFTGGNVTLTCQVSGaYPPAKILWLRNLTQ-PEviiqpSSRHLITQDGqnsTLTIHNCSQDLDEGYYICRADSP 292
Cdd:cd20958    6 PMGnlTAVAGQTLRLHCPVAG-YPISSITWEKDGRRlPL-----NHRQRVFPNG---TLVIENVQRSSDEGEYTCTARNQ 76

                 ..
gi 578823903 293 VG 294
Cdd:cd20958   77 QG 78

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 578823903 216 PMKTCFT-----GGNVTLTCQVSGAYPPAKILWLRN---LTQPEVIIQPSSRHLITqdgQNSTLTIHnCSQDLDEGYYIC 287
Cdd:cd05761    7 PVITGFTspvveGDEITLTCTTSGSKPAADIRWFKNdkeLKGVKEVQESGAGKTFT---VTSTLRFR-VDRDDDGVAVIC 82

                 ....*
gi 578823903 288 RADSP 292
Cdd:cd05761   83 RVDHE 87

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 578823903 205 VQIRGpsllSEPMKTCFTGGNVTLTCQVSGaYPPAKILWLRNltqPEVIIQPSSRHLITQDGqnSTLTIHNCSQdLDEGY 284
Cdd:cd05730    4 IRARQ----SEVNATANLGQSVTLACDADG-FPEPTMTWTKD---GEPIESGEEKYSFNEDG--SEMTILDVDK-LDEAE 72

                         90       100
                 ....*....|....*....|
gi 578823903 285 YICRADSPVGVREMEIWLSV 304
Cdd:cd05730   73 YTCIAENKAGEQEAEIHLKV 92

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 215 EPMKTCFTGGNVTLTC--QVSGAYPPAKILWLR------------NLTQPEVIIQPSSRHLI----TQDGQNSTLTIHNC 276
Cdd:cd05718    6 PTEVTGFLGGSVTLPCslTSPGTTKITQVTWMKigagssqnvavfHPQYGPSVPNPYAERVEflaaRLGLRNATLRIRNL 85

                         90       100
                 ....*....|....*....|....*....
gi 578823903 277 SQDlDEGYYICR-ADSPVGVREMEIWLSV 304
Cdd:cd05718   86 RVE-DEGNYICEfATFPQGNRQGTTWLRV 113

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 210 PSLLSEPM-KTCFTGGNVTLTCQVSGaYPPAKILWLRNLTQPE-VIIQPSSRH---LITQDGQnstLTIHNcSQDLDEGY 284
Cdd:cd05765    1 PALVNSPThQTVKVGETASFHCDVTG-RPQPEITWEKQVPGKEnLIMRPNHVRgnvVVTNIGQ---LVIYN-AQPQDAGL 75

                         90       100
                 ....*....|....*....|
gi 578823903 285 YICRADSPVGVREMEIWLSV 304
Cdd:cd05765   76 YTCTARNSGGLLRANFPLSV 95

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 578823903  40 VTLHCGNISGLRGQVTWYRNNSEPvfllssnsSLRPAEPRFSLVDATSLHIESLSLGDEGIYTCQ 104
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPL--------PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 578823903 211 SLLSEPMK-TCFTGGNVTLTCQVSGAyPPAKILWLRNlTQPeviIQPSSRHLITQDGQNSTLTIhNCSQDLDEGYYICRA 289
Cdd:cd05747    5 TILTKPRSlTVSEGESARFSCDVDGE-PAPTVTWMRE-GQI---IVSSQRHQITSTEYKSTFEI-SKVQMSDEGNYTVVV 78

                         90
                 ....*....|....
gi 578823903 290 DSPVGVREMEIWLS 303
Cdd:cd05747   79 ENSEGKQEAQFTLT 92

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 226 VTLTCQVSGAyPPAKILW---LRNLTQPEVIIqpSSRHLITQDGQNSTLTIHNCsQDLDEGYYICRADSPVGVREMEIWL 302
Cdd:cd05869   20 ITLTCEASGD-PIPSITWrtsTRNISSEEKTL--DGHIVVRSHARVSSLTLKYI-QYTDAGEYLCTASNTIGQDSQSMYL 95

                 ..
gi 578823903 303 SV 304
Cdd:cd05869   96 EV 97

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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 578823903 223 GGNVTLTCQVSGAYPPAKilWLRNLTQpeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRA 289
Cdd:cd20967   12 GHKIRLTVELADPDAEVK--WYKDGQE----LQSSSKVIFESIGAKRTLTVQQASLA-DAGEYQCVA 71

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 228 LTCQVSGAYPPAKILWLRNLTQPEVIIqpSSRHLItQDGQN----STLTIHncSQDLDEG-YYICRADS---PVGvREME 299
Cdd:cd05759   20 LTCRARGAKPAAEIIWFRDGEQLEGAV--YSKELL-KDGKRettvSTLLIT--PSDLDTGrTFTCRARNeaiPNG-KETS 93

                 ....*
gi 578823903 300 IWLSV 304
Cdd:cd05759   94 ITLDV 98

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 210 PSLLSEPMKTCFTGGN-VTLTCQVSGaYPPAKILWLRNL-TQPEVIIQPSSRHLITQDGqNSTLTIHNCSQDlDEGYYIC 287
Cdd:cd20954    2 PRWIVEPVDANVAAGQdVMLHCQADG-FPTPTVTWKKATgSTPGEYKDLLYDPNVRILP-NGTLVFGHVQKE-NEGHYLC 78

                 ....*..
gi 578823903 288 RADSPVG 294
Cdd:cd20954   79 EAKNGIG 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 211 SLLSEPMKT-CFTGGNVTLTCQVSGAyPPAKILWLR-----NLTQPEVIIQPSSRHLITQDGQNSTltiHNCSqdlDEGY 284
Cdd:cd05722    3 YFLSEPSDIvAMRGGPVVLNCSAESD-PPPKIEWKKdgvllNLVSDERRQQLPNGSLLITSVVHSK---HNKP---DEGF 75

                 ....*
gi 578823903 285 YICRA 289
Cdd:cd05722   76 YQCVA 80

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 213 LSEPMKTCFTGGNVTLTCQVSGAYPP-AKILWLRNLT-QPEVIIQPSSRHliTQDG---QNSTLTIhnCSQDLDEGY-YI 286
Cdd:cd00098    4 LLPPSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVpLTSGVSTSSPVE--PNDGtysVTSSLTV--PPSDWDEGAtYT 79

                 ....
gi 578823903 287 CRAD 290
Cdd:cd00098   80 CVVT 83

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903 210 PSLLSEPMKTCFTGGN-VTLTCQVSGAyPPAKILWLRNlTQPEVI--IQPSSRHLITQDGQNSTLTI-HNCSQDLDEGYY 285
Cdd:cd07693    1 PRIVEHPSDLIVSKGDpATLNCKAEGR-PTPTIQWLKN-GQPLETdkDDPRSHRIVLPSGSLFFLRVvHGRKGRSDEGVY 78

                         90
                 ....*....|
gi 578823903 286 ICRADSPVGV 295
Cdd:cd07693   79 VCVAHNSLGE 88

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903   225 NVTLTCQVSG-AYPPAKILWLR--NLTQPEVI----------IQPSSRHLITQDGQNS----TLTIHNCSQDlDEGYYIC 287
Cdd:smart00406   1 SVTLSCKFSGsTFSSYYVSWVRqpPGKGLEWLgyigsngssyYQESYKGRFTISKDTSkndvSLTISNLRVE-DTGTYYC 79

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823903    39 NVTLHCG--NISGLRGQVTWYR--NNSEPVFLLSSNSSLRPAEP-----RFSLVDATS-----LHIESLSLGDEGIYTCQ 104
Cdd:smart00406   1 SVTLSCKfsGSTFSSYYVSWVRqpPGKGLEWLGYIGSNGSSYYQesykgRFTISKDTSkndvsLTISNLRVEDTGTYYCA 80

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578823903 223 GGNVTLTCQVSGAyPPAKILWLRNLTQpeviiQPSSRHLITQDgqnSTLTIHNCsQDLDEGYYICRADSPVG 294
Cdd:cd05725   12 DDSAEFQCEVGGD-PVPTVRWRKEDGE-----LPKGRYEILDD---HSLKIRKV-TAGDMGSYTCVAENMVG 73

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). 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. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.

                         10        20
                 ....*....|....*....|...
gi 578823903 269 STLTIHNCSQDlDEGYYICRADS 291
Cdd:cd05862   66 STLTIDNVTLS-DKGLYTCAASS 87

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 578823903 218 KTCFTGGNVTLTCQV-SGAYPpaKILWLR----NLTQ------PEVIIQPSSrhLITQDGQNSTLTIHNCSQDlDEGYYI 286
Cdd:cd04974   11 QTVVLGSDVEFHCKVySDAQP--HIQWLKhvevNGSKygpdglPYVTVLKVA--GVNTTGEENTLTISNVTFD-DAGEYI 85

                         90
                 ....*....|....*..
gi 578823903 287 CRADSPVGVREMEIWLS 303
Cdd:cd04974   86 CLAGNSIGLSFHSAWLT 102

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578823903  38 ENVTLHC-GNISGLRGQVTWYRNNSepvfLLSSNSSlrpaeprfslvdatSLHIESLSLGDEGIYTCQ 104
Cdd:cd05752   16 EKVTLTCqGFYSPEQNSTQWYHNGT----LISSTSS--------------SYRIVAATVNDSGEYRCQ 65