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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 258547137  32 VQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 258547137 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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 258547137  32 VQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 258547137 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 258547137    38 SQTVSTGESIILSCSVPNTlPNGPVLWFKGTGpnRKLIYNfkqgnfPRVKEIGDttkpgNTDFSTRIREISLADAGTYYC 117
Cdd:smart00410   3 SVTVKEGESVTLSCEASGS-PPPEVTWYKQGG--KLLAES------GRFSVSRS-----GSTSTLTISNVTPEDSGTYTC 68

                   .
gi 258547137   118 V 118
Cdd:smart00410  69 A 69

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 258547137  32 VQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLAD 111
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPAD 81

                         90       100
                 ....*....|....*....|....*....
gi 258547137 112 AGTYYCVKFIKGRAIK-EYQSGRGTQVFV 139
Cdd:cd16097   82 AGTYYCVKFRKGSPDDvEFKSGAGTELSV 110

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 258547137   34 QTEMSQTVSTGESIILSCSVPNTLPNGP--VLWFKGTGPN--RKLIYNFKQGNFPRVKEIGDT--TKPGNTDFSTRIREI 107
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEAStsVYWYRQPPGKgpTFLIAYYSNGSEEGVKKGRFSgrGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 258547137  108 SLADAGTYYCVKFIKGraikEYQSGRGTQVFVT 140
Cdd:pfam07686  81 TLSDSGTYTCAVIPSG----EGVFGKGTRLTVL 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 258547137  32 VQQTEMSQTVSTGESIILSCSVPnTLPNGPVLWFKGTgPNRKLIYNFKQGNFPRVKEIGD---TTKPGNTDFSTRIREIS 108
Cdd:cd04983    1 VTQSPQSLSVQEGENVTLNCNYS-TSTFYYLFWYRQY-PGQGPQFLIYISSDSGNKKKGRfsaTLDKSRKSSSLHISAAQ 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 258547137 109 LADAGTYYCVKFIKGRAIKeYQSGRGTQVFVT 140
Cdd:cd04983   79 LSDSAVYFCALSESGGTGK-LTFGKGTRLTVE 109

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 258547137  32 VQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWF--KGTGPNRKLIY--NFKQGNFP-RVKEIGDttkpgNTDFSTRIRE 106
Cdd:cd04980    3 MTQSPASLSVSPGERVTISCKASQSISSNYLAWYqqKPGQAPKLLIYyaSTLHSGVPsRFSGSGS-----GTDFTLTISS 77

                         90
                 ....*....|...
gi 258547137 107 ISLADAGTYYCVK 119
Cdd:cd04980   78 VEPEDAAVYYCQQ 90

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 258547137  36 EM-SQTVSTGESIILSCSVPNTLPNGPVLWFKGTgpnrkliynfkqgnfprvKEIGDTTKPGNTDF-------STRIREI 107
Cdd:cd05895    5 EMkSQEVAAGSKLVLRCETSSEYPSLRFKWFKNG------------------KEINRKNKPENIKIqkkkkksELRINKA 66

                         90
                 ....*....|
gi 258547137 108 SLADAGTYYC 117
Cdd:cd05895   67 SLADSGEYMC 76

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) delta chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the delta 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 antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and 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 standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 258547137  32 VQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWFKGTgPNRKLIYNFKQGNFPRVKEIGDTT---KPGNTDFSTRIREIS 108
Cdd:cd07706    2 VTQAQPDVSVQVGEEVTLNCRYETSWTNYYLFWYKQL-PSGEMTFLIRQDSSEQNAKSGRYSvnfQKAQKSISLTISALQ 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 258547137 109 LADAGTYYCVkFIKGRAIKEYQSGRGTQVFV 139
Cdd:cd07706   81 LEDSAKYFCA-LSLPYDTDKLIFGKGTRLTV 110

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). 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. In addition nectins heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls), nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 258547137  33 QQTEMSQTVS--TGESIILSCSVPNTLPN---GPVLWFKGTGPNRK--LIYNFKQGN--FPRVKEIGDTTKPGNTDFSTR 103
Cdd:cd05886    1 QTVQVNDSMSgfIGTDVVLHCSFANPLPSvkiTQVTWQKSTNGSKQnvAIYNPSMGVsvLPPYRERVTFLNPSFTDGTIR 80

                         90
                 ....*....|....
gi 258547137 104 IREISLADAGTYYC 117
Cdd:cd05886   81 LSRLELEDEGVYIC 94

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 258547137   38 SQTVSTGESIILSCSVPNTLPNGPVLWFKGTGpnrkliynfkqgnfprVKEIGDTTKPGN---TDFSTRIREISLADAGT 114
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGG----------------TLIESLKVKHDNgrtTQSSLLISNVTKEDAGT 68

                  ....
gi 258547137  115 YYCV 118
Cdd:pfam00047  69 YTCV 72