Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  33 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 112
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1060604609 113 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 143
Cdd:cd16097    81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  33 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 112
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1060604609 113 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 143
Cdd:cd16097    81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609   39 KSVSVAAGESATLRCAmTSLIPVGPIMWFRGAGagRELIYNQKeghfprvTTVSeltkRNNLDFSISISNITPADAGTYY 118
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVTWYKQGG--KLLAESGR-------FSVS----RSGSTSTLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|....
gi 1060604609  119 CVkfrkGSPDDVEFKSgaGTELSV 142
Cdd:smart00410  68 CA----ATNSSGSASS--GTTLTV 85

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  33 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 112
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1060604609 113 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 143
Cdd:cd16097    81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

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 1060604609  36 QPEKSVSVAAGESATLRCAMTSLI--PVGPIMWFRG-AGAGRE---LIYNQKEGHFPRVTTVSELTKRNNLDFSISISNI 109
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseASTSVYWYRQpPGKGPTfliAYYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1060604609 110 TPADAGTYYCVKFrkgspDDVEFKSGAGTELSVR 143
Cdd:pfam07686  81 TLSDSGTYTCAVI-----PSGEGVFGKGTRLTVL 109

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 1060604609  34 VIQPEKSVSVAAGESATLRCAMTSlIPVGPIMWFRG-AGAGRELIYNQ--KEGHFPRVTTVSELTKRNNlDFSISISNIT 110
Cdd:cd04983     1 VTQSPQSLSVQEGENVTLNCNYST-STFYYLFWYRQyPGQGPQFLIYIssDSGNKKKGRFSATLDKSRK-SSSLHISAAQ 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1060604609 111 PADAGTYYCVKFRKGSPDDVEFksGAGTELSVR 143
Cdd:cd04983    79 LSDSAVYFCALSESGGTGKLTF--GKGTRLTVE 109

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  36 QPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRgagAGRELIYNQKEGHFPRVTTVSELTkrnnldfsisISNITPADAG 115
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSK---EGGTLIESLKVKHDNGRTTQSSLL----------ISNVTKEDAG 67

                          90
                  ....*....|....*....
gi 1060604609 116 TYYCVKFRKGSPDDVEFKS 134
Cdd:pfam00047  68 TYTCVVNNPGGSATLSTSL 86

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 1060604609  33 QVIQPEKSVSVAAGESATLRCAMTSLIP--VGPIMWFRGAGAGRELI--YNQKEG-HFP-----RVTTVSELTKRNNLdf 102
Cdd:cd05718     1 QRVQVPTEVTGFLGGSVTLPCSLTSPGTtkITQVTWMKIGAGSSQNVavFHPQYGpSVPnpyaeRVEFLAARLGLRNA-- 78

                          90       100
                  ....*....|....*....|....*.
gi 1060604609 103 SISISNITPADAGTYYC--VKFRKGS 126
Cdd:cd05718    79 TLRIRNLRVEDEGNYICefATFPQGN 104

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  35 IQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRgagagreliYNQ---KEGHF-------PRVTTV--SELTKRNNLDF 102
Cdd:cd07700     2 LQTPGSLLVQTNQTVKMSCEAKTSPKNTRIYWLR---------QRQapsKDSHFeflaswdPSKGIVygEGVDQEKLIIL 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1060604609 103 S--------ISISNITPADAGTYYCVKFrkGSPddvEFKSGAGTELSV 142
Cdd:cd07700    73 SdsdssryiLSLMSVKPEDSGTYFCMTV--GSP---ELIFGTGTKLSV 115

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609   48 SATLRC-AMTSLIPVGPIMWFR-GAGAGRE-LIYNQKEGHF-------PRVTTVSELTKRnnlDFSISISNITPADAGTY 117
Cdd:smart00406   1 SVTLSCkFSGSTFSSYYVSWVRqPPGKGLEwLGYIGSNGSSyyqesykGRFTISKDTSKN---DVSLTISNLRVEDTGTY 77

                   ..
gi 1060604609  118 YC 119
Cdd:smart00406  78 YC 79

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 1060604609  36 QPEKSVSVAAGESATLRCAMTSL-IPVGPIMWFRG-AGAGRE-LIY------NQKEGHFPRVTTVSELTKRNNLdFSISI 106
Cdd:cd04982     3 QPQLSITREESKSVTISCKVSGIdFSTTYIHWYRQkPGQALErLLYvsstsaVRKDSGKTKNKFEARKDVGKST-STLTI 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1060604609 107 SNITPADAGTYYCVKFRKGSPDDVE-FksGAGTELSV 142
Cdd:cd04982    82 TNLEKEDSATYYCAYWESGSGYYIKvF--GSGTKLIV 116

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 1060604609  34 VIQPEkSVSVAAGESATLRCAMTSL-IPVGPIMWfrgagagreliYNQKEGHFPRvtTVSELTKR-------------NN 99
Cdd:cd04984     2 LTQPS-SLSVSPGETVTITCTGSSGnISGNYVNW-----------YQQKPGSAPR--YLIYEDKHrpsgipdrfsgskSG 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1060604609 100 LDFSISISNITPADAGTYYCvkfrkGSPDDVEFKSGAGTELSV 142
Cdd:cd04984    68 NTASLTISGAQTEDEADYYC-----QVWDSNSYVFGGGTKLTV 105

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  39 KSVSVAAGESATLRCAMTSLIPVGPIMWFRGagaGRELIYNQKEGH--FPRVTTVSELtkrnnldfsiSISNITPADAGT 116
Cdd:cd05895     7 KSQEVAAGSKLVLRCETSSEYPSLRFKWFKN---GKEINRKNKPENikIQKKKKKSEL----------RINKASLADSGE 73

                  ...
gi 1060604609 117 YYC 119
Cdd:cd05895    74 YMC 76

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  35 IQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNldFSISISNITPADA 114
Cdd:cd05716     1 SVGPEVVTGVEGGSVTIQCPYPPKYASSRKYWCKWGSEGCQTLVSSEGVVPGGRISLTDDPDNGV--FTVTLNQLRKEDA 78

                  ....*.
gi 1060604609 115 GTYYCV 120
Cdd:cd05716    79 GWYWCG 84

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 1060604609  34 VIQPEKSVSVAAGESATLRCamtsliPVG--PI---MWFRGagaGRELIYNQKEGHFPRVTTVseltkrnnldfsisISN 108
Cdd:cd20958     3 FIRPMGNLTAVAGQTLRLHC------PVAgyPIssiTWEKD---GRRLPLNHRQRVFPNGTLV--------------IEN 59

                          90
                  ....*....|...
gi 1060604609 109 ITPA-DAGTYYCV 120
Cdd:cd20958    60 VQRSsDEGEYTCT 72

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 1060604609  49 ATLRCAMTSlIPVGPIMWFRGagagRELIYNQKEGHFPRVTTVSELTkrnnldfsisISNITPADAGTYYCV 120
Cdd:cd00096     1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLT----------ISNVTLEDSGTYTCV 57

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  39 KSVSVAAGESATLRC--AMTSLIPVGPIMWFR-GAGAGRE--LIYNQKEGH--FPRVT-TVSELTKRNNLDFSISISNIT 110
Cdd:cd05888     1 DVVTVVLGQDAKLPCfyRGDSGEQVGQVAWARvDAGEGAQeiALLHSKYGLhvFPAYEgRVEQPPPPRPADGSVLLRNAV 80

                  ....*....
gi 1060604609 111 PADAGTYYC 119
Cdd:cd05888    81 QADEGEYEC 89

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604609  32 LQVIQPEKSVSVAAGESATLRCAMT-SLIPVGP--IMWFRGAGAGRE---------LIYNQ-KEGHFPRVTTVSELTKRn 98
Cdd:cd20960     1 LLITSAQTEIKKVAGENVTLPCHHQlGLEDQGTldIEWLLLPSDKVEkvvitysgdRVYNHyYPALKGRVAFTSNDLSG- 79

                          90       100
                  ....*....|....*....|....*..
gi 1060604609  99 nlDFSISISNITPADAGTYYCvKFRKG 125
Cdd:cd20960    80 --DASLNISNLKLSDTGTYQC-KVKKA 103