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 1624525587 115 PSVTLFPPSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYS 194
Cdd:cd07699     2 PSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVYT 81

                          90
                  ....*....|....*...
gi 1624525587 195 CQVMHEG--STVEKTVAP 210
Cdd:cd07699    82 CEVTHEGlsSTITKSFNR 99

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 1624525587 115 PSVTLFPPSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYS 194
Cdd:cd07699     2 PSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVYT 81

                          90
                  ....*....|....*...
gi 1624525587 195 CQVMHEG--STVEKTVAP 210
Cdd:cd07699    82 CEVTHEGlsSTITKSFNR 99

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1624525587  131 KATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYSCQVMHEGSTVE 205
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKEP 75

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 1624525587 115 PSVTLFPPSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYS 194
Cdd:cd07699     2 PSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVYT 81

                          90
                  ....*....|....*...
gi 1624525587 195 CQVMHEG--STVEKTVAP 210
Cdd:cd07699    82 CEVTHEGlsSTITKSFNR 99

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1624525587  131 KATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYSCQVMHEGSTVE 205
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKEP 75

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 1624525587 115 PSVTLFPPSSEELQANK-ATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNK--YAASSYLSLTPEQWRSRR 191
Cdd:cd16093     2 PTVSLHAPSREEFLGNRtATFVCLATGFSPKTISFKWLRNGKEVTSSTGAVVEEPKEDGKtlYSATSFLTITESEWKSQT 81

                          90
                  ....*....|....*..
gi 1624525587 192 SYSCQVMHEGSTVEKTV 208
Cdd:cd16093    82 EFTCEFKHKGEIVEKNA 98

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 1624525587 115 PSVTLFPPSSEEL-QANKATLVCLMNDFYPGILTVTWKADGTPI-TQGVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRS 192
Cdd:cd05768     1 PSVYLLPPPEEELsLNETVTLTCLVKGFYPEDIFVSWLQNGEPLpSADYKTTAPVPESDGSFFVYSKLNVSTADWNSGDV 80

                          90
                  ....*....|....*....
gi 1624525587 193 YSCQVMHEGS---TVEKTV 208
Cdd:cd05768    81 FSCVVGHEALplqFTQKSI 99

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy mu 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 mu chains. It belongs to a family 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 118 TLFP-PSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEmTTPSKQSNNKYAASSYLSLTPEQWRSRRSYSCQ 196
Cdd:cd21819     3 TLFPlVSCGSSTSDPVTVGCLATDFLPDSITFSWTDDNNSLTTGVK-TYPSVLTGGTYTASSQLQVPESEWKSKENFYCK 81

                          90
                  ....*....|....
gi 1624525587 197 VMHEGSTVEKTVAP 210
Cdd:cd21819    82 VEHPGGNKEVPVPK 95

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 115 PSVTLFPPSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSK-QSNNKYAASSYLSLTPEQWRSRRSY 193
Cdd:cd04985     2 PTVFPLQSATKSQSNGPVALGCLISDYFPESITVSWQKNTNSITSGFTRTFPVVlRSGGDYSCSSQLTVPLQEWNSGEVY 81

                  ....*....
gi 1624525587 194 SCQVMHEGS 202
Cdd:cd04985    82 KCQVQHSAS 90

HLA class II histocompatibility antigen DO alpha; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the nonclassical MHC class II (MHCII) protein, HLA-DO, which binds HLA-DM and influences the repertoire of peptides presented by MHCII proteins. In complex with HLA-DM, HLA-DO adopts a classical MHCII structure, with alterations near the a subunit's 310 helix. HLA-DO binds to HLA-DM at the same sites implicated in MHCII interaction, and kinetic analysis showed that HLA-DO acts as a competitive inhibitor by acting as a substrate mimic. Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells indicate that it may be of physiological importance and has inspired further research. 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 1624525587 115 PSVTLFPPSSEEL-QANkaTLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPeqwRSRRSY 193
Cdd:cd21004     3 PRVTVLPKSRVELgQPN--ILICIVDNIFPPVINITWLRNGQTVTEGVAQTSFYSQPDHLFRKFHYLPFVP---SAEDVY 77

                  ....*...
gi 1624525587 194 SCQVMHEG 201
Cdd:cd21004    78 DCKVEHWG 85

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 1624525587 115 PSVTLFPPSSEELQaNKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPeqwRSRRSYS 194
Cdd:cd05766     4 PSVKVSPTKTGPLE-HPNLLVCSVTGFYPAEIEVKWFRNGQEETAGVVSTELIPNGDWTFQILVMLETTP---RRGDVYT 79

                  ....*
gi 1624525587 195 CQVMH 199
Cdd:cd05766    80 CQVEH 84

T cell receptor (TCR) gamma chain constant immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) constant (C) 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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 115 PSVTLFPPSSEELQANKA-TLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKqSNNKYAASSYLSLTPEQwrSRRSY 193
Cdd:cd07697     2 PKPTIFLPSIAETEKQKAgTYLCLLENFFPDVIKIHWREKKSDTILESQEGNTEK-TKDTYMKFSWLTVPKKS--LGKEH 78

                          90
                  ....*....|....
gi 1624525587 194 SCQVMHEG-STVEK 206
Cdd:cd07697    79 RCIYKHENnKNGVK 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 116 SVTLFPPSS-EELQANKATLVCLMNDFYPGILTVTWKADGTPITqgVEMTTPSKQSNNKYAASSYLSLTPEQWRSRRSYS 194
Cdd:cd21818     1 SPTVFPLSLcPSLSSDPVVIGCLVQGFFPEPVNVTWNYSGKGGT--ARNFPAMLASGGRYTQSSQLTLPADQCPEGEAYK 78

                          90
                  ....*....|....
gi 1624525587 195 CQVMHEGSTVEKTV 208
Cdd:cd21818    79 CSVQHYSPSQDLNV 92

Class II major histocompatibility complex (MHC) beta 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 Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) I-E. 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). I-A and I-E molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. 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 1624525587 112 KATPSVTLFPPSSEELQANKaTLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEqwrSRR 191
Cdd:cd20998     4 RVEPTVTVYPTKTQPLEHHN-LLVCSVSDFYPGNIEVRWFRNGKEEKTGIVSTGLVRNGDWTFQTLVMLETVPQ---SGE 79

                          90
                  ....*....|....*..
gi 1624525587 192 SYSCQVMHEGSTVEKTV 208
Cdd:cd20998    80 VYTCQVEHPSLTDPVTV 96

Class I major histocompatibility complex (MHC) beta-2-microglobulin; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in beta-2-microglobulin (beta2m). Beta2m is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). Beta2m is structured as a beta-sandwich domain composed of two facing beta-sheets (four stranded and three stranded), that is typical of the C-type immunoglobulin superfamily. This structure is stabilized by an intramolecular disulfide bridge connecting two Cys residues in the facing beta-sheets. In vivo, MHC-I continuously exposes beta2m on the cell surface, where it may be released to plasmatic fluids, transported to the kidneys, degraded, and finally excreted.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 114 TPSV---TLFPPssEELQANkaTLVCLMNDFYPGILTVTWKADGTPITqGVEMTTPSKQSNNKYAASSYLSLTPEqwrSR 190
Cdd:cd05770     2 TPKVqvySRFPA--ENGKPN--VLNCYVSGFHPPDIEIRLLKNGVKIE-DVEQSDLSFSKDWTFYLLKYTEFTPT---KG 73

                          90
                  ....*....|....*...
gi 1624525587 191 RSYSCQVMHEGSTVEKTV 208
Cdd:cd05770    74 DEYACRVRHNTLSEPKIY 91

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld; 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 human leukocyte antigen (HLA) H2Db and H2Ld. H-2Ld complexed with peptide QL9 (or p2Ca) and complexed with influenza virus peptide NP366-374 (ASNEN-METM), respectively are high-affinity alloantigens for the 2C T cell receptor (TCR). The a1-a2 super domains of H-2Ld, H-2Db, and H-2Kb closely superimpose. 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 1624525587 111 PKAtpSVTLFPPSSEELqankaTLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwr 188
Cdd:cd21018     6 PKA--HVTHHPRSKGEV-----TLRCWALGFYPADITLTWQLNGEELTQDMELveTRPAGDGTFQKWASVVVPLGKEQ-- 76

                          90
                  ....*....|...
gi 1624525587 189 srrSYSCQVMHEG 201
Cdd:cd21018    77 ---NYTCRVYHEG 86

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 115 PSVTLFPPSSEELqANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEqwrSRRSYS 194
Cdd:cd21005     3 PEVTVLSRSPVNL-GEPNILICFIDKFSPPVVNVTWLRNGRPVTEGVSETVFLPRDDHLFRKFHYLTFLPS---TDDFYD 78

                  ....*..
gi 1624525587 195 CQVMHEG 201
Cdd:cd21005    79 CEVDHWG 85

CH2 domain (second 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 second immunoglobulin constant-1 set domain (IgC) of alpha 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. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 114 TPSVTLFPPSSEELQANK-ATLVCLMNDFY-PGILTVTWKADG--TPITQgvemtTPSKQSNNKYAASSYLSLTPEQWRS 189
Cdd:cd04986     1 QPRLSLQRPALEDLLLGSnASLTCTLSGLKdPEGATFTWEPSGgkEAIQG-----PPERDSCGCYSVSSVLPGCAEPWNS 75

                          90
                  ....*....|....*....
gi 1624525587 190 RRSYSCQVMHEGSTVEKTV 208
Cdd:cd04986    76 GDTFSCTVTHPESKGTLTA 94

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-A; 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-A. 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). I-A and I-E molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E a gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 115 PSVTLFPpSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEqwrSRRSYS 194
Cdd:cd21006     3 PQATVFP-KSPVLLGQPNTLICFVDNIFPPVINITWLRNSKSVTDGVYETSFLVNRDHSFHKLSYLTFIPS---DDDIYD 78

                  ....*..
gi 1624525587 195 CQVMHEG 201
Cdd:cd21006    79 CKVEHWG 85

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A; 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 human leukocyte antigen (HLA) A. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-A gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. HLA-A2 is associated with spontaneous abortions, HIV, and Hodgkin lymphoma. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1624525587 130 NKATLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21027    18 HEATLRCWALSFYPAEITLTWQRDGEDQTQDTELveTRPAGDGTFQKWAAVVVPSGQEQ-----RYTCHVQHEG 86

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; 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 human histocompatibility antigen (HLA) DQ and mouse I-A. 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). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP 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. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. 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 response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. 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, and 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 1624525587 115 PSVTLFPPSSEELQANKaTLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLSLTPEQwrsRRSYS 194
Cdd:cd21001     4 PTVTISPSRTEALNHHN-LLVCSVTDFYPGQIKVRWFRNDQEETAGVVSTPLIRNGDWTFQILVMLEMTPQR---GDVYT 79

                  ....*
gi 1624525587 195 CQVMH 199
Cdd:cd21001    80 CHVEH 84

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624525587 133 TLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21016    21 TLRCWALGFYPADITLTWQKDGEELTQDMEFveTRPAGDGTFQKWAAVVVPLGKEQ-----SYTCHVYHEG 86

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-2; 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 QA-2. Qa-2 is a nonclassical MHC Ib antigen, which has been implicated in both innate and adaptive immune responses, as well as embryonic development. Qa-2 has an unusual peptide binding specificity in that it requires two dominant C-terminal anchor residues and is capable of associating with a substantially more diverse array of peptide sequences than other nonclassical MHC. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624525587 133 TLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21014    20 TLRCWALGFYPADITLTWQLNGEELTQDMELveTRPAGDGTFQKWASVVVPLGKEQ-----NYTCHVNHEG 85

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; 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 alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1624525587 130 NKATLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21023    18 HEATLRCWALGFYPAEITLTWQRDGEEQTQDTELveTRPAGDGTFQKWAAVVVPPGEEQ-----RYTCHVQHEG 86

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G; 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 (HLA) G. HLA-G histocompatibility antigen (also known as human leukocyte antigen G ; HLA-G) is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogs. This class I molecule is a heterodimer consisting of a heavy chain and light chain, beta-2-microglobulin. The heavy chain is anchored in the membrane. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I and class II. 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. MHC class II molecules play a key role in the initiation of the antigen-specific immune repose. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1624525587 131 KATLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21022    18 EATLRCWALGFYPAEIILTWQRDGEDQTQDVELveTRPAGDGTFQKWAAVVVPSGEEQ-----RYTCHVQHEG 85

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd; 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 H2-Dd. Mouse MHC is composed of 11 subclasses. It includes the classical MHC class I (MHC-Ia) that comprises H-2D, H-2K and H-2L subclasses, the non-classical MHC class I (MHCIb) that comprises H-2Q, H-2M and H-2T subclasses, the classical MHC class II (MHC-IIa) that includes H-2A(I-A) and H-2E(I-E) subclasses, and the non-classical MHC class II (MHC-IIb) comprises H-2M and H-2O. H-2K, H-2D, and H-2L are 80 to 90% homologous at the amino acid level yet appear to be involved in different recognition reactions and are differentially expressed on lymphoid cells. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624525587 133 TLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21020    21 TLRCWALGFYPADITLTWQLNGEELTQEMELveTRPAGDGTFQKWASVVVPLGKEQ-----KYTCHVEHEG 86

H-2 class I histocompatibility complex TLA (thymus leukemia antigen); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the major histocompatibility complex (MHC) H-2 class I histocompatibility complex TLA (thymus leukemia antigen). The murine MHC class I histocompatibility TLA (Thymus leukemia antigen), which is encoded in the T region by T3 and T18 genes, is expressed mainly by intestinal epithelial cells and thymocytes. The murine TLAs are class I, beta-2-microglobulin-associated glycoproteins. The TLA function is not defined by antigen presentation, but rather by its relatively high affinity binding to CD8-alpha-alpha compared with CD8-alpha-beta. The existence of a human homolog for murine TLA remains unresolved. This group is a member of the C1-set Ig domains, which have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624525587 133 TLVCLMNDFYPGILTVTWKADGTPITQGVEM--TTPSKQSNNKYAASSYLSLTPEQwrsrrSYSCQVMHEG 201
Cdd:cd21012    21 TLRCWALGFYPAHITLTWQLNGEELIQDTELveTRPAGDGTFQKWAAVVVPSGEEQ-----KYTCHVYHEG 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624525587 120 FPPSSEELQA-----NKATLVCLMNDFYPGILTVTWKADGTpitqgVEMT-TPSKQSNNK---YAASSYLSLTPEQWRSR 190
Cdd:cd16085     1 VPPTLEVTQQptmvwNQVNVTCQVEKFYPQRLQLTWLENGN-----VSRTeTPSTLTVNKdgtYNWTSWLLVNVSAHRED 75

                          90
                  ....*....|.
gi 1624525587 191 RSYSCQVMHEG 201
Cdd:cd16085    76 VVLTCQVEHDG 86