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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 442631518   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 442631518   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518    80 PRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILtvgsytytSDQRFQATHhqDTEDWTLQIKWAQKRDAGMYECQI 159
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*.
gi 442631518   160 STqPVRSYFVRLNVVV 175
Cdd:smart00410  71 TN-SSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   73 PYFDpSTPRNVTALMGKSAYLSCRVRNLANKTVSWiRHRDIHIltvgsytyTSDQRFQAthHQDTEDWTLQIKWAQKRDA 152
Cdd:pfam07679   1 PKFT-QKPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPL--------RSSDRFKV--TYEGGTYTLTISNVQPDDS 68

                  ....*.
gi 442631518  153 GMYECQ 158
Cdd:pfam07679  69 GKYTCV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   184 PDLHVDKGSTINLTCTVKFSPEPpaYIFWYHHEEVINYDSSRggvsvITEKGDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 442631518   264 V---ASVRVHV 271
Cdd:smart00410  75 GsasSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518    80 PRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILtvgsytytSDQRFQATHhqDTEDWTLQIKWAQKRDAGMYECQI 159
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*.
gi 442631518   160 STqPVRSYFVRLNVVV 175
Cdd:smart00410  71 TN-SSGSASSGTTLTV 85

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518  79 TPRNVTALMGKSAYLSCRVRNLANKT-VSWIRHRD----IHILTVGS----YTYTSDQRFQATHhQDTEDWTLQIKWAQK 149
Cdd:cd00099    4 SPRSLSVQEGESVTLSCEVSSSFSSTyIYWYRQKPgqgpEFLIYLSSskgkTKGGVPGRFSGSR-DGTSSFSLTISNLQP 82

                         90
                 ....*....|....
gi 442631518 150 RDAGMYECQISTQP 163
Cdd:cd00099   83 EDSGTYYCAVSESG 96

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   79 TPRNVTALMGKSAYLSCRVRNLANKT---VSWIRHRDIHILTVGSYTYTSDQ-------RFQATHHQDTEDWTLQIKWAQ 148
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKGPTFLIAYYSNGSeegvkkgRFSGRGDPSNGDGSLTIQNLT 81

                          90       100
                  ....*....|....*....|....*...
gi 442631518  149 KRDAGMYECQISTQPVRSYF--VRLNVV 174
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEGVFGkgTRLTVL 109

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 442631518 194 INLTCTVKFSPEPpaYIFWYHHEEVINYDSSRGGVSVitekgdVTTSFLLIQNADLADSGKYSCAPSNADVASVRVHV 271
Cdd:cd00096    1 VTLTCSASGNPPP--TITWYKNGKPLPPSSRDSRRSE------LGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518 184 PDLHVDKGSTINLTCTvkFSPEPPAYIFWYHH------EEVINYDS-----SRGGVSVITEKgDVTTSFLLIQNADLADS 252
Cdd:cd04983    6 QSLSVQEGENVTLNCN--YSTSTFYYLFWYRQypgqgpQFLIYISSdsgnkKKGRFSATLDK-SRKSSSLHISAAQLSDS 82

                 ....*.
gi 442631518 253 GKYSCA 258
Cdd:cd04983   83 AVYFCA 88

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 442631518  73 PYFDPSTPRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILTVGSYTYTSDQRFQATHHQDTEDW-TLQIKWAQKRD 151
Cdd:cd04974    1 PILQAGLPANQTVVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKYGPDGLPYVTVLKVAGVNTTGEEnTLTISNVTFDD 80

                 ....*.
gi 442631518 152 AGMYEC 157
Cdd:cd04974   81 AGEYIC 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518   78 STPRNVTALMGKSAYLSCRVRNLANKTVSWIRHrdihiltvGSYTYTSDQRFQATHHQDTedwTLQIKWAQKRDAGMYEC 157
Cdd:pfam13927   6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKN--------GEPISSGSTRSRSLSGSNS---TLTISNVTRSDAGTYTC 74

                  ...
gi 442631518  158 QIS 160
Cdd:pfam13927  75 VAS 77

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule 2; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-2, Necl-2 (also known as cell adhesion molecule 1 (CADM1), SynCAM1, IGSF4A, Tslc1, sgIGSF, and RA175). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518  81 RNVTALMGKSAYLSCRVRN-------LANKTVSWIRHRDIHILtvgsytytSDQRFQATHHQDTEdWTLQIKWAQKRDAG 153
Cdd:cd05881    4 EDVTVVEGEVATISCRVKNsddsviqLLNPNRQTIYFRDFRPL--------KDSRFQLVNFSSSE-LRVSLTNVSISDEG 74

                         90       100
                 ....*....|....*....|
gi 442631518 154 MYECQISTQPVRSYFVRLNV 173
Cdd:cd05881   75 RYFCQLYTDPPQEAYTTITV 94

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442631518 190 KGSTINLTCTVKfsPEPPAYIFWYHHEEVIN-YDSSRGGVSViTEKGDVTTSFLLIQNADLADSGKYSCAPSNA 262
Cdd:cd05735   17 KGQKKEMSCTAH--GEKPIIVRWEKEDTIINpSEMSRYLVTT-KEVGDEVISTLQILPTVREDSGFFSCHAINS 87

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 442631518  76 DPSTPRNVTALMGKSAYLSCRVRNLANKTVSWIRHRDIHILTVGSYTYTSDQRfqathhqdtedwTLQIKWAQKRDAGMY 155
Cdd:cd20970    5 TPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT------------TLTIRNIRRSDMGIY 72

                 ....*
gi 442631518 156 ECQIS 160
Cdd:cd20970   73 LCIAS 77

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 442631518 180 ILGGPDLHVDKGSTINLTCtVKFSPEPPAYIFWYHHEEVINydssrGGVSVIT----EKGDVTTSFLLIQNADLADSGKY 255
Cdd:cd05759    4 IEGGPVISLQAGVPYNLTC-RARGAKPAAEIIWFRDGEQLE-----GAVYSKEllkdGKRETTVSTLLITPSDLDTGRTF 77

                 ....*.
gi 442631518 256 SCAPSN 261
Cdd:cd05759   78 TCRARN 83

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442631518 187 HVDKGSTINLTCTVKFSPEPPAyIFWYHHEEVINydssrggvsvitekgdVTTSFLLIQNADLADSGKYSC 257
Cdd:cd05752   11 TVFQGEKVTLTCQGFYSPEQNS-TQWYHNGTLIS----------------STSSSYRIVAATVNDSGEYRC 64

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 442631518 178 ATILGG-PDL-HVDKGSTINLTCTVkfSPEPPAYIFWYHHEEVINYdSSRGGVSVitEKGdvTTSFLLIQNADLADSGKY 255
Cdd:cd05737    1 ARVLGGlPDVvTIMEGKTLNLTCNV--WGDPPPEVSWLKNDQALAF-LDHCNLKV--EAG--RTVYFTINGVSSEDSGKY 73

                 .
gi 442631518 256 S 256
Cdd:cd05737   74 G 74

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442631518  79 TPRNVTALMGKSAYLSCRVRNLANKT--VSWIRHRD-------IHILTVGSYTYTSDQ---RFQATHHQDTEDWTLQIKW 146
Cdd:cd04982    4 PQLSITREESKSVTISCKVSGIDFSTtyIHWYRQKPgqalerlLYVSSTSAVRKDSGKtknKFEARKDVGKSTSTLTITN 83

                         90
                 ....*....|.
gi 442631518 147 AQKRDAGMYEC 157
Cdd:cd04982   84 LEKEDSATYYC 94

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 442631518 184 PDLHVDKGSTINLTCTVKFSPEPPayIFWYHHEEVINYDSSRGGVsvitekgDVTTSFLLIQNADLADSGKYSCAPSNAD 263
Cdd:cd20976    9 KDLEAVEGQDFVAQCSARGKPVPR--ITWIRNAQPLQYAADRSTC-------EAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|.
gi 442631518 264 ---VASVRVHV 271
Cdd:cd20976   80 gqvSCSAWVTV 90

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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 442631518 188 VDKGSTINLTCTVkfSPEPPAYIFWYHHEEVINYDSSRggVSVITEK-GDVTtsfLLIQNADLADSGKYSCAPSN-ADVA 265
Cdd:cd05892   12 VLEGDPVRLECQI--SAIPPPQIFWKKNNEMLQYNTDR--ISLYQDNcGRIC---LLIQNANKKDAGWYTVSAVNeAGVV 84

                 .
gi 442631518 266 S 266
Cdd:cd05892   85 S 85

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 442631518 184 PDLHVDKGSTINLTCTVKFSPEPPAYIFWYHHEE------VINYDSSRGgvSVITEK----GDVTTSFLLIQNADLADSG 253
Cdd:cd04984    6 SSLSVSPGETVTITCTGSSGNISGNYVNWYQQKPgsapryLIYEDKHRP--SGIPDRfsgsKSGNTASLTISGAQTEDEA 83

                 ....*
gi 442631518 254 KYSCA 258
Cdd:cd04984   84 DYYCQ 88

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

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gi 442631518  78 STPRNVTALMGKSAYLSCRVRNLANKTVSWirHRDIHILTVGSYtytsdqrfqathhQDTEDWTLQIKWAQKRDAGMYEC 157
Cdd:cd05725    2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRW--RKEDGELPKGRY-------------EILDDHSLKIRKVTAGDMGSYTC 66

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gi 442631518 158 Q 158
Cdd:cd05725   67 V 67

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

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gi 442631518 188 VDKGSTINLTCTVKFSPePPAyIFWYHHEEVINYDSSRGGVSVITEkGDVTTSFLLIQnadlaDSGKYSCAPSNA---DV 264
Cdd:cd20969   14 VDEGHTVQFVCRADGDP-PPA-ILWLSPRKHLVSAKSNGRLTVFPD-GTLEVRYAQVQ-----DNGTYLCIAANAggnDS 85

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gi 442631518 265 ASVRVHV 271
Cdd:cd20969   86 MPAHLHV 92

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; 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. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

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gi 442631518 186 LHVDKGSTINLTctVKFSPEPPAYIFWYHhEEVINYDSSRggvsVITEKGDVTTSfLLIQNADLADSGKYS-CA--PSNA 262
Cdd:cd05748    2 IVVRAGESLRLD--IPIKGRPTPTVTWSK-DGQPLKETGR----VQIETTASSTS-LVIKNAKRSDSGKYTlTLknSAGE 73

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gi 442631518 263 DVASVRVHV 271
Cdd:cd05748   74 KSATINVKV 82