Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 3 (C1 repeat 2). 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 that 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, but with much less affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEISQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNKDGTYNWISCLLVNISALEENMVVTC 180
Cdd:cd16085    1 VPPTLEVTQQPTMVWNQVNVTCQVEKFYPQRLQLTWLENGNVSRTETPSTLTVNKDGTYNWTSWLLVNVSAHREDVVLTC 80

                         90
                 ....*....|....*.
gi 568920629 181 QVEHDGQAEVIETHTV 196
Cdd:cd16085   81 QVEHDGQPAVTKNHTL 96

Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 3 (C1 repeat 2). 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 that 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, but with much less affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEISQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNKDGTYNWISCLLVNISALEENMVVTC 180
Cdd:cd16085    1 VPPTLEVTQQPTMVWNQVNVTCQVEKFYPQRLQLTWLENGNVSRTETPSTLTVNKDGTYNWTSWLLVNVSAHREDVVLTC 80

                         90
                 ....*....|....*.
gi 568920629 181 QVEHDGQAEVIETHTV 196
Cdd:cd16085   81 QVEHDGQPAVTKNHTL 96

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629   98 FIQVPPTLEISQQPTmvwnviiVTCQIQKFYPPRFQVTWLENG-NISRREVPFTLIVNKDGTYNWISCLLVNISALEENM 176
Cdd:pfam07654   2 YVFPPSPEELGKPNT-------LTCLVTGFYPPDITVTWLKNGqEVTEGVKTTPPSPNSDWTYQLSSYLTVTPSDWESGD 74

                          90
                  ....*....|
gi 568920629  177 VVTCQVEHDG 186
Cdd:pfam07654  75 EYTCRVEHEG 84

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629    5 PAARAVPKQTVTFTCRSHGFFPRNLTLKWFKNGNEI-SHLETSVEPEETSVSYRVSSTVQVVLEPRDVRSQIICEVDHVT 83
Cdd:pfam07654   5 PPSPEELGKPNTLTCLVTGFYPPDITVTWLKNGQEVtEGVKTTPPSPNSDWTYQLSSYLTVTPSDWESGDEYTCRVEHEG 84

                  .
gi 568920629   84 L 84
Cdd:pfam07654  85 L 85

Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 3 (C1 repeat 2). 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 that 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, but with much less affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEISQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNKDGTYNWISCLLVNISALEENMVVTC 180
Cdd:cd16085    1 VPPTLEVTQQPTMVWNQVNVTCQVEKFYPQRLQLTWLENGNVSRTETPSTLTVNKDGTYNWTSWLLVNVSAHREDVVLTC 80

                         90
                 ....*....|....*.
gi 568920629 181 QVEHDGQAEVIETHTV 196
Cdd:cd16085   81 QVEHDGQPAVTKNHTL 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629  98 FIQVPPTLEISQQPTMVwnviivTCQIQKFYPPRFQVTWLENGN-ISRREVPFTLIVNKDGTYNWISCLLVNISALEENM 176
Cdd:cd00098    3 TLLPPSPEEKGGGKVTL------VCLVSGFYPKDITVTWLKNGVpLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDEGA 76

                         90
                 ....*....|....*.
gi 568920629 177 VVTCQVEHDGQAEVIE 192
Cdd:cd00098   77 TYTCVVTHESLKSPLS 92

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629   98 FIQVPPTLEISQQPTmvwnviiVTCQIQKFYPPRFQVTWLENG-NISRREVPFTLIVNKDGTYNWISCLLVNISALEENM 176
Cdd:pfam07654   2 YVFPPSPEELGKPNT-------LTCLVTGFYPPDITVTWLKNGqEVTEGVKTTPPSPNSDWTYQLSSYLTVTPSDWESGD 74

                          90
                  ....*....|
gi 568920629  177 VVTCQVEHDG 186
Cdd:pfam07654  75 EYTCRVEHEG 84

Immunoglobulin C-Type;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568920629   120 VTCQIQKFYPPRFQVTWLENGNISRREV-PFTLIVNKDGTYNWISCLLVNISALEENMVVTCQVEHDG 186
Cdd:smart00407   4 LVCLVSGFYPPDITVTWLRNGQEVTEGVsTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTHEG 71

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 568920629   1 MVSGPAARAVPKQTVTFTCRSHGFFPRNlTLKWFKNGNEIsHLETSVEPEETSVSYRVSSTVQVVLEPRDVRSQIICEVD 80
Cdd:cd05761    8 VITGFTSPVVEGDEITLTCTTSGSKPAA-DIRWFKNDKEL-KGVKEVQESGAGKTFTVTSTLRFRVDRDDDGVAVICRVD 85

                         90
                 ....*....|
gi 568920629  81 HVTLDRAPLR 90
Cdd:cd05761   86 HESLTSTPKQ 95

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEISQQPTMVWNVII-VTCQIQKFYPPRFQVTWLENGNI-SRREVPFTLIVNKDGTYNWISCLLVNISALEenmVV 178
Cdd:cd05766    2 VQPSVKVSPTKTGPLEHPNlLVCSVTGFYPAEIEVKWFRNGQEeTAGVVSTELIPNGDWTFQILVMLETTPRRGD---VY 78

                 ....*.
gi 568920629 179 TCQVEH 184
Cdd:cd05766   79 TCQVEH 84

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). 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. 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. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629   2 VSGPAARAVPKQTVTFTCRSHGFFPRnLTLKWFKNGNEISHLETSVEPEETSVSYRVSSTVQVVLEPRDVRSQIICEVDH 81
Cdd:cd05884   10 ISGFTSPVMEGDHIQLTCKTSGSKPA-ADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSSLDFHVDRDDDGVAITCRVDH 88

                 ....*..
gi 568920629  82 VTLDRAP 88
Cdd:cd05884   89 ESLTATP 95

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629   6 AARAVPKQTVTFTCRSHGFFPRNLTLKWFKNGNEISHLETS--VEPEETSvSYRVSSTVQVVLEPRDVRSqiiCEVDHVT 83
Cdd:cd21029    9 SRPSPGDGHLQLSCHVTGFYPRPIEVTWLRDGQEQMDGTQSggILPNHDG-TYQLRKTLDIAPGEGAGYS---CRVDHSS 84

                 ...
gi 568920629  84 LDR 86
Cdd:cd21029   85 LKQ 87

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, delta, epsilon, gamma, and mu chains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. 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 is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568920629   5 PAARAVPKQTVTFTCRSHGFFPRNLTLKWFKNGNEISHLETSVEPEETSVSYRVSSTVQVVLEPRDVRSQ--IICEVDH 81
Cdd:cd04985    9 SATKSQSNGPVALGCLISDYFPESITVSWQKNTNSITSGFTRTFPVVLRSGGDYSCSSQLTVPLQEWNSGevYKCQVQH 87

Class I major histocompatibility complex (MHC) alpha chain, alpha3 immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEISQQPTMVwNVIIVTCQIQKFYPPRFQVTWLENG-----NISRREV-PftlivNKDGTYN-WIScllVNISALE 173
Cdd:cd07698    1 DPPKVHVTHHPRSD-GESTLRCWALGFYPAEITLTWQRDGedqtqDMELVETrP-----NGDGTFQkWAA---VVVPSGE 71

                         90
                 ....*....|....*....
gi 568920629 174 ENmVVTCQVEHDGQAEVIE 192
Cdd:cd07698   72 EQ-RYTCHVQHEGLPEPLT 89

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B. MIC-A and MIC-B are homologs that serve as stress-inducible antigens on epithelial and epithelially derived cells. Both serve as ligands for the widely expressed activating immunoreceptor NKG2D, a C-type lectin-like activating immunoreceptor. MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding and the IgC domain is involved in oligomerization and molecular interactions.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 568920629  10 VPKQTVTFTCRSHGFFPRNLTLKWFKNGNEISH 42
Cdd:cd21017   14 ASEGNITVTCRASGFYPWNITLSWRQDGVSLSH 46

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. 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. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568920629 120 VTCQIQKFYPPRFQVTWLENGN-ISRREVPFTLIVNKDGTYNWISCLLVNISALEENMVVTCQVEHDGQAEVIE 192
Cdd:cd07699   21 LVCLINKFYPGFATVTWKVDGStVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVYTCEVTHEGLSSTIT 94

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and related proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DQ. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. Two autoimmune diseases in which HLA-DQ is involved are celiac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 100 QVPPTLEISQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNK-DGTYNWISCLLVNISALEenmVV 178
Cdd:cd21008    1 EVPEVTVFPKSPVTLGQPNTLICLVDNIFPPVINITWLSNGHSVTEGVSETSFLSKsDHSFLKISYLTFLPSADD---IY 77

                         90
                 ....*....|....*.
gi 568920629 179 TCQVEHDGQAEVIETH 194
Cdd:cd21008   78 DCKVEHWGLDKPLLKH 93

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu heavy chains. This domain is found on the Fc fragment. 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 is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629  98 FIQVPPTLEISQQPTmvwnVIIVtCQIQKFYPPRFQVTWLENGNI---SRREVPFTLIVNKDGTYNWISCLLVNISALEE 174
Cdd:cd16093    5 SLHAPSREEFLGNRT----ATFV-CLATGFSPKTISFKWLRNGKEvtsSTGAVVEEPKEDGKTLYSATSFLTITESEWKS 79

                         90
                 ....*....|..
gi 568920629 175 NMVVTCQVEHDG 186
Cdd:cd16093   80 QTEFTCEFKHKG 91

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR. HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. HLA-DR is also involved in several autoimmune conditions, disease susceptibility, and disease resistance including seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, schizophrenia, Goodpasture syndrome, systemic lupus erythematosus, Alzheimers, tuberculoid leprosy, and Hashimoto's thyroiditis. HLA-DR molecules are upregulated in response to signaling. HLA-DR is an alphabeta heterodimer cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain, and a cytoplasmic tail. Both alpha and beta chains are anchored in the membrane. The DR beta chain is encoded by 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus, DRB1*. The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 100 QVPPTLEI---SQQPTMVWNVIIvtCQIQKFYPPRFQVTWLENGNISRREVPFT-LIVNKDGTYNwisCLLVNISALEEN 175
Cdd:cd21000    1 RVEPKVTVypaKTQPLQHHNLLV--CSVNGFYPGSIEVRWFRNGQEEKAGVVSTgLIQNGDWTFQ---TLVMLETVPRSG 75

                 ....*....
gi 568920629 176 MVVTCQVEH 184
Cdd:cd21000   76 EVYTCQVEH 84

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568920629 116 NVIIvtCQIQKFYPPRFQVTWLENG-NISRREVPFTLIVNKDGTYNWISCLlvNISALEENmVVTCQVEHDG 186
Cdd:cd05767   19 NTLI--CFVDNFFPPVINVTWLRNGqPVTDGVSETVFLPREDHSFRKFSYL--PFTPSEGD-IYDCRVEHWG 85

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. 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. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: 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 568920629   5 PAARAVPKQTVTFTCRSHGFFPRNLTLKWFKNGNEISH-LETSVEPEETSVSYRVSSTVQVVLEPRDVRSQIICEVDHVT 83
Cdd:cd07699    9 PSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSgVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVYTCEVTHEG 88

                 .
gi 568920629  84 L 84
Cdd:cd07699   89 L 89

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. 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 is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 118 IIVTCQIQKFYPPRFQVTWLENGN-ISRREVPFTLIVNkdGTYNWISCLLVNISALEENMVVTCQVEHDG 186
Cdd:cd21818   18 VVIGCLVQGFFPEPVNVTWNYSGKgGTARNFPAMLASG--GRYTQSSQLTLPADQCPEGEAYKCSVQHYS 85

T cell receptor (TCR) beta chain constant immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the T cell receptor (TCR) beta chain constant immunoglobulin domain. 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 includes the variable domain of the beta chain. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The antigen binding site is formed by the variable domains of the alpha and beta chains, located at the N-terminus of each chain. Alpha/beta TCRs recognize antigens differently from gamma/delta TCRs.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568920629  12 KQTVTFTCRSHGFFPRNLTLKWFKNGNEI-SHLET-SVEPEETSVSYRVSSTVQV-VLEPRDVRSQIICEVDH 81
Cdd:cd05769   18 KRKATLVCLATGFYPDHVSLSWKVNGKEVkDGVATdPQALRENTSTYSLSSRLRVsATEWFNPRNTFTCIVKF 90

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DR. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DR is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DRA1 and HLA-DRB1, that are adjacent to each other on chromosome band 6p21.31. Susceptibility to multiple sclerosis and rheumatoid arthritis are associated with the human histocompatibility leukocyte antigen HLA-DR2 and HLA-DR4, respectively. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 101 VPPTLEI-SQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNKDGTYNWISCLLVNISALEEnmVVT 179
Cdd:cd21007    1 VPPEVTVlTNSPVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLPSTED--VYD 78

                         90
                 ....*....|....*
gi 568920629 180 CQVEHDGQAEVIETH 194
Cdd:cd21007   79 CRVEHWGLDEPLLKH 93

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629  10 VPKQTVTFTCRSHGFFPRNLTLKWFKNGNEISHLEtsVEPEET----SVSYRVSSTVQVvlePRDVRSQIICEVDHVTLD 85
Cdd:cd21021   13 VTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKE--FEPKDVlpngDGTYQGWITLAV---PPGEEQRYTCQVEHPGLD 87

                 ....
gi 568920629  86 RaPL 89
Cdd:cd21021   88 Q-PL 90

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of T10, T22, and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of the murine H-2T-encoded T10, T22, and similar proteins. T10 and T22 are highly related nonclassical major histocompatibility complex (MHC) class Ib proteins that bind to certain gammadelta T cell receptors (TCRs) in the absence of other components. Classical MHC class I (class Ia) molecules participate in immune responses by presenting peptide antigens to cytolytic alpha beta T cells. Many nonclassical MHC class I (class Ib) molecules have distinct antigen-binding capabilities, suggesting that they have evolved for specific tasks that are distinct from those of MHC class Ia. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568920629  11 PKQTVTFTCRSHGFFPRNLTLKWFKNGNEISHLETSVEPEETSvsyrvSSTVQ---VVLEPRDVRSQIICEVDH 81
Cdd:cd21016   16 PEGDVTLRCWALGFYPADITLTWQKDGEELTQDMEFVETRPAG-----DGTFQkwaAVVVPLGKEQSYTCHVYH 84

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. 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 is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568920629 102 PPTLEISQQPTMvwnviIVTCQIQKFYPPRFQVTWLENGnisrREVPFTLIVN------KDGTYNWISCLLVNISALEEN 175
Cdd:cd05768    8 PPEEELSLNETV-----TLTCLVKGFYPEDIFVSWLQNG----EPLPSADYKTtapvpeSDGSFFVYSKLNVSTADWNSG 78

                         90
                 ....*....|.
gi 568920629 176 MVVTCQVEHDG 186
Cdd:cd05768   79 DVFSCVVGHEA 89

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-E; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) I-E. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568920629 102 PPTLEISQQPTMVWNVIIVTCQIQKFYPPRFQVTWLENGNISRREVPFTLIVNKD 156
Cdd:cd21005    3 PEVTVLSRSPVNLGEPNILICFIDKFSPPVVNVTWLRNGRPVTEGVSETVFLPRD 57