Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512  344 TCLVGGDVTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNCSQDqDGGFYFCRAENPVGVRAA 423
Cdd:pfam07679  11 EVQEGESARFTCTVTG-TPDPEVSWFKD----GQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEA 84

                  ....*.
gi 404501512  424 DIWLSV 429
Cdd:pfam07679  85 SAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512    60 GEVHENVTLRCGSLSGSRGLVTWYRNDSEPaflvssnsslPPAAPRFSLE---DAGALRIEALRLEDDGNYTCR-EVLNE 135
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKL----------LAESGRFSVSrsgSTSTLTISNVTPEDSGTYTCAaTNSSG 75

                           90
                   ....*....|
gi 404501512   136 THWFPVQLRV 145
Cdd:smart00410  76 SASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512  344 TCLVGGDVTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNCSQDqDGGFYFCRAENPVGVRAA 423
Cdd:pfam07679  11 EVQEGESARFTCTVTG-TPDPEVSWFKD----GQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEA 84

                  ....*.
gi 404501512  424 DIWLSV 429
Cdd:pfam07679  85 SAELTV 90

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 404501512 351 VTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNcSQDQDGGFYFCRAENPVGVRAA 423
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLTISN-VTLEDSGTYTCVASNSAGGSAS 67

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512    60 GEVHENVTLRCGSLSGSRGLVTWYRNDSEPaflvssnsslPPAAPRFSLE---DAGALRIEALRLEDDGNYTCR-EVLNE 135
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKL----------LAESGRFSVSrsgSTSTLTISNVTPEDSGTYTCAaTNSSG 75

                           90
                   ....*....|
gi 404501512   136 THWFPVQLRV 145
Cdd:smart00410  76 SASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 404501512  161 TLPNGTLYAARGSQVDFSCCSAAQPPPEVEWW---IQTHSSVSESLGKNLSANSFTLMLMSKNLQGNYTCSATN 231
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYkngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 404501512 172 GSQVDFSCCSAAQPPPEVEWwiqTHSsvseslGKNLSANSFTLM-----LMSKNLQ----GNYTCSATNVLSRRQRKVTT 242
Cdd:cd20978   16 GQDVTLPCQVTGVPQPKITW---LHN------GKPLQGPMERATvedgtLTIINVQpedtGYYGCVATNEIGDIYTETLL 86

                 .
gi 404501512 243 E 243
Cdd:cd20978   87 H 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512  344 TCLVGGDVTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNCSQDqDGGFYFCRAENPVGVRAA 423
Cdd:pfam07679  11 EVQEGESARFTCTVTG-TPDPEVSWFKD----GQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEA 84

                  ....*.
gi 404501512  424 DIWLSV 429
Cdd:pfam07679  85 SAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 404501512  344 TCLVGGDVTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNcSQDQDGGFYFCRAEN 416
Cdd:pfam13927  12 TVREGETVTLTCEATG-SPPPTITWYKN----GEPISSGSTRSRSLSGSNSTLTISN-VTRSDAGTYTCVASN 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 404501512 343 KTCLVGGDVTLTCQVEGANPPArIQWLRNLTQPETAIQpssRYVITQQGQSssLTIHNCSQDqDGGFYFCRAENPVG 419
Cdd:cd20970   12 VTAREGENATFMCRAEGSPEPE-ISWTRNGNLIIEFNT---RYIVRENGTT--LTIRNIRRS-DMGIYLCIASNGVP 81

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 404501512 349 GDVTLTCQVEgANPPARIQWLRNLTqpETAIQPSSRYVITqqgqSSSLTIHNCSQDQDGGFYFCRAENPVG 419
Cdd:cd04967   20 KKVALNCRAR-ANPVPSYRWLMNGT--EIDLESDYRYSLV----DGTLVISNPSKAKDAGHYQCLATNTVG 83

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 404501512 329 VVQISSPLLASrpmktclVGGDVTLTCQVEGANPPARIQWLR-------------NLTQPETAIQPSSRYVITQQGQSS- 394
Cdd:cd00099    1 VTQSPRSLSVQ-------EGESVTLSCEVSSSFSSTYIYWYRqkpgqgpefliylSSSKGKTKGGVPGRFSGSRDGTSSf 73

                         90
                 ....*....|....*...
gi 404501512 395 SLTIHNcSQDQDGGFYFC 412
Cdd:cd00099   74 SLTISN-LQPEDSGTYYC 90

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 404501512 348 GGDVTLTCQVEGANPPARIQWLRN---LTQPETAIQPSSRYVITqqgQSSSLTIHnCSQDQDGGFYFCRAENPvGVRAAD 424
Cdd:cd05761   19 GDEITLTCTTSGSKPAADIRWFKNdkeLKGVKEVQESGAGKTFT---VTSTLRFR-VDRDDDGVAVICRVDHE-SLTSTP 93

                         90
                 ....*....|.
gi 404501512 425 iwLSVKEPLNV 435
Cdd:cd05761   94 --KQTQQVLEV 102

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 404501512 343 KTCLVGGDVTLTCQVEGaNPPARIQW---LRNLTQPETaiQPSSRYVITQQGQSSSLTIHNCsQDQDGGFYFCRAENPVG 419
Cdd:cd05732   11 QTAVELEQITLTCEAEG-DPIPEITWrraTRGISFEEG--DLDGRIVVRGHARVSSLTLKDV-QLTDAGRYDCEASNRIG 86

                         90
                 ....*....|
gi 404501512 420 VRAADIWLSV 429
Cdd:cd05732   87 GDQQSMYLEV 96

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 404501512 349 GDVTLTCQVEgANPPARIQWLRNLTqpETAIQPSSRYVITqqgqSSSLTIHNCSQDQDGGFYFCRAENPVG 419
Cdd:cd05850   21 EKVTLACRAR-ASPPATYRWKMNGT--ELKMEPDSRYRLV----AGNLVISNPVKAKDAGSYQCLASNRRG 84

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 351 VTLTCQVEGaNPPARIQWLRNLTqpETAIQPSSRYVITQqgqsSSLTIHNCSQDQDGGFYFCRAENPVGV 420
Cdd:cd05848   22 VILNCEARG-NPVPTYRWLRNGT--EIDTESDYRYSLID----GNLIISNPSEVKDSGRYQCLATNSIGS 84

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 335 PLLASRPMKTCLVGGD-VTLTCQVEGaNPPARIQWLRNLTQPET-AIQPSSRYVITQQGQSSSLTI-HNCSQDQDGGFYF 411
Cdd:cd07693    1 PRIVEHPSDLIVSKGDpATLNCKAEG-RPTPTIQWLKNGQPLETdKDDPRSHRIVLPSGSLFFLRVvHGRKGRSDEGVYV 79

                 ....*....
gi 404501512 412 CRAENPVGV 420
Cdd:cd07693   80 CVAHNSLGE 88

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 404501512   60 GEVHENVTLRC---GSLSGSRGLVTWYR----NDSEPAFLVSSNSSLPPAAP-RFSLEDA-----GALRIEALRLEDDGN 126
Cdd:pfam07686   8 VALGGSVTLPCtysSSMSEASTSVYWYRqppgKGPTFLIAYYSNGSEEGVKKgRFSGRGDpsngdGSLTIQNLTLSDSGT 87

                          90       100
                  ....*....|....*....|..
gi 404501512  127 YTCREVLNETHWF--PVQLRVT 146
Cdd:pfam07686  88 YTCAVIPSGEGVFgkGTRLTVL 109

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 404501512 343 KTCLVGGDVTLTCQVEgANPPARIQWLRNLTQPETAIQPSS--------RYVITQQGQSSSLTIHNCSQDqDGGFYFCRA 414
Cdd:cd04974   11 QTVVLGSDVEFHCKVY-SDAQPHIQWLKHVEVNGSKYGPDGlpyvtvlkVAGVNTTGEENTLTISNVTFD-DAGEYICLA 88

                         90
                 ....*....|....
gi 404501512 415 ENPVGVRAADIWLS 428
Cdd:cd04974   89 GNSIGLSFHSAWLT 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 404501512  161 TLPNGTLYAARGSQVDFSCCSAAQPPPEVEWW---IQTHSSVSESLGKNLSANSFTLMLMSKNLQGNYTCSATN 231
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYkngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 404501512 343 KTCLVGGDVTLTCQVEGaNPPARIQWLRNLTQpetaIQPSSRYVITQQ-GQSSSLTIHNCSQdQDGGFYFCRAENPVGVR 421
Cdd:cd05744   10 LEVQEGRLCRFDCKVSG-LPTPDLFWQLNGKP----VRPDSAHKMLVReNGRHSLIIEPVTK-RDAGIYTCIARNRAGEN 83

                 ....*...
gi 404501512 422 AADIWLSV 429
Cdd:cd05744   84 SFNAELVV 91

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 404501512  64 ENVTLRCgSLSGSRGL--VTWYRND--SEPAFLVSSNSSLPP----AAPRFSLEDAGA----LRIEALRLEDDGNYTC 129
Cdd:cd00099   14 ESVTLSC-EVSSSFSStyIYWYRQKpgQGPEFLIYLSSSKGKtkggVPGRFSGSRDGTssfsLTISNLQPEDSGTYYC 90

Immunoglobulin (Ig) lambda light chain variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, lambda type, variable (V) domain. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512  54 SEAVAIGEvheNVTLRCGSLSGSRG--LVTWY--RNDSEPAFLVSSNSSLPPAAP-RFS---LEDAGALRIEALRLEDDG 125
Cdd:cd04984    7 SLSVSPGE---TVTITCTGSSGNISgnYVNWYqqKPGSAPRYLIYEDKHRPSGIPdRFSgskSGNTASLTISGAQTEDEA 83

                 ....
gi 404501512 126 NYTC 129
Cdd:cd04984   84 DYYC 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 329 VVQISSPLLASRPmktclvGGDVTLTCQVEGAnPPARIQWLRNltqpETAIQPSSRYVITQQGQSSSLTIHNCSQdQDGG 408
Cdd:cd05736    2 VIRVYPEFQAKEP------GVEASLRCHAEGI-PLPRVQWLKN----GMDINPKLSKQLTLIANGSELHISNVRY-EDTG 69

                         90
                 ....*....|..
gi 404501512 409 FYFCRAENPVGV 420
Cdd:cd05736   70 AYTCIAKNEGGV 81

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 404501512 344 TCLVGGDVTLTCQVEGaNPPARIQWLRNltqpETAIQPSSRY-VITQQGQSSSLTIHNCSQdQDGGFYFCRAENPVGVRA 422
Cdd:cd05737   12 TIMEGKTLNLTCNVWG-DPPPEVSWLKN----DQALAFLDHCnLKVEAGRTVYFTINGVSS-EDSGKYGLVVKNKYGSET 85

                 ....*..
gi 404501512 423 ADIWLSV 429
Cdd:cd05737   86 SDVTVSV 92

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512  60 GEVHENVTLRCGSLSGSRGL----VTWYRNDSE-----------PAFLVSSNSSLPPAAPRFSLEDAgALRIEALRLEDD 124
Cdd:cd20989   11 GFLGGSVTLPCHLLPPNMVThvsqVTWQRHDEHgsvavfhpkqgPSFPESERLSFVAARLGAELRNA-SLAMFGLRVEDE 89

                 ....*
gi 404501512 125 GNYTC 129
Cdd:cd20989   90 GNYTC 94

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 404501512 348 GGDVTLTCQVEGaNPPARIQWLRNLTQpetaIQPSSRYVITQQGQSSSLTIHNCSQDqDGGFYFCRAENPVG 419
Cdd:cd20972   16 GSKVRLECRVTG-NPTPVVRWFCEGKE----LQNSPDIQIHQEGDLHSLIIAEAFEE-DTGRYSCLATNSVG 81

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 404501512 340 RPMK--TCLVGGDVTLTCQVEGaNPPARIQWLRNLTQ-PEtaiqpSSRYVITQQGqssSLTIHNCSQDQDGGFYFCRAEN 416
Cdd:cd20958    5 RPMGnlTAVAGQTLRLHCPVAG-YPISSITWEKDGRRlPL-----NHRQRVFPNG---TLVIENVQRSSDEGEYTCTARN 75

                 ....*.
gi 404501512 417 PVGVRA 422
Cdd:cd20958   76 QQGQSA 81

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 348 GGDVTLTCQVEGANPP-ARIQWLRNLTQpetaiqpssryviTQQGQSSSLTIHNCSQDQDGGfYFCRAENPVGV-RAADI 425
Cdd:cd20937   17 GDSVTMTCEVSSSNPEyTTVSWLKDGTS-------------LKKQNTFTLNLREVTKDQSGK-YCCQVSNDVGPgRSEEV 82

                 ....*
gi 404501512 426 WLSVK 430
Cdd:cd20937   83 FLQVQ 87

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 404501512 353 LTCQVEGANPPARIQWLRNLTQPETAIqpSSRYVI---TQQGQSSSLTIHNCSQDqDGGFYFCRAEN---PVGvRAADIW 426
Cdd:cd05759   20 LTCRARGAKPAAEIIWFRDGEQLEGAV--YSKELLkdgKRETTVSTLLITPSDLD-TGRTFTCRARNeaiPNG-KETSIT 95

                 ...
gi 404501512 427 LSV 429
Cdd:cd05759   96 LDV 98

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, 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 hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 348 GGDVTLTCQVEGANPPArIQWLRNLTQPETAIQPSSRYVITQQGqsssLTIHNCSQDqDGGFYFCRAENPVGVRAADIWL 427
Cdd:cd20949   14 GQSATILCEVKGEPQPN-VTWHFNGQPISASVADMSKYRILADG----LLINKVTQD-DTGEYTCRAYQVNSIASDMQER 87

                 ..
gi 404501512 428 SV 429
Cdd:cd20949   88 TV 89

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404501512 348 GGDVTLTCQVEGaNPPARIQWLRNLTQPETAIQPSSRYVitqqgqSSSLTIHNCSQDQDGGFYFCRAENPVGVRAADIWL 427
Cdd:cd05868   14 GEDGTLICRANG-NPKPSISWLTNGVPIEIAPTDPSRKV------DGDTIIFSKVQERSSAVYQCNASNEYGYLLANAFV 86

                 ..
gi 404501512 428 SV 429
Cdd:cd05868   87 NV 88

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 404501512  64 ENVTLRCGSLSGSRG---LVTWYRNDSE-------------PAFLVSSNSSLPPAAPRFSLEDAgALRIEALRLEDDGNY 127
Cdd:cd05718   15 GSVTLPCSLTSPGTTkitQVTWMKIGAGssqnvavfhpqygPSVPNPYAERVEFLAARLGLRNA-TLRIRNLRVEDEGNY 93

                 ..
gi 404501512 128 TC 129
Cdd:cd05718   94 IC 95