HLAG_HUMAN
ID HLAG_HUMAN Reviewed; 338 AA.
AC P17693;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=HLA class I histocompatibility antigen, alpha chain G;
DE AltName: Full=HLA G antigen;
DE AltName: Full=MHC class I antigen G;
DE Contains:
DE RecName: Full=Soluble HLA class I histocompatibility antigen, alpha chain G;
DE Short=sHLA-G {ECO:0000303|PubMed:23737137};
DE Flags: Precursor;
GN Name=HLA-G {ECO:0000303|PubMed:1570318, ECO:0000312|HGNC:HGNC:4964};
GN Synonyms=HLA-6.0, HLAG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RC TISSUE=Fetal eye;
RX PubMed=2336406; DOI=10.1093/nar/18.8.2189;
RA Shukla H., Swaroop A., Srivastava R., Weissman S.M.;
RT "The mRNA of a human class I gene HLA G/HLA 6.0 exhibits a restricted
RT pattern of expression.";
RL Nucleic Acids Res. 18:2189-2189(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3480534; DOI=10.1073/pnas.84.24.9145;
RA Geraghty D.E., Koller B.H., Orr H.T.;
RT "A human major histocompatibility complex class I gene that encodes a
RT protein with a shortened cytoplasmic segment.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:9145-9149(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Ishitani A., Geraghty D.E.;
RL Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10727083; DOI=10.3109/10425179909033955;
RA Hampe A., Coriton O., Andrieux N., Carn G., Lepourcelet M., Mottier S.,
RA Dreano S., Gatius M.T., Hitte C., Soriano N., Galibert F.;
RT "A 356-Kb sequence of the subtelomeric part of the MHC class I region.";
RL DNA Seq. 10:263-299(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RX PubMed=1570318; DOI=10.1073/pnas.89.9.3947;
RA Ishitani A., Geraghty D.E.;
RT "Alternative splicing of HLA-G transcripts yields proteins with primary
RT structures resembling both class I and class II antigens.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:3947-3951(1992).
RN [7]
RP ALTERNATIVE SPLICING (ISOFORM 4), AND TISSUE SPECIFICITY (ISOFORM 4).
RX PubMed=7589701;
RA Moreau P., Teyssier M., Kirszenbaum M., Gluckman E., Gourand L.,
RA Carosella E., Dausset J.;
RT "HLA-G mRNA forms in human trophoblasts and peripheral blood lymphocytes:
RT potential use in prenatal diagnosis.";
RL Folia Biol. (Praha) 40:431-438(1994).
RN [8]
RP ALTERNATIVE SPLICING (ISOFORMS 5 AND 6).
RX PubMed=7989753;
RA Fujii T., Ishitani A., Geraghty D.E.;
RT "A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic
RT acid containing intron 4.";
RL J. Immunol. 153:5516-5524(1994).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM 4).
RX PubMed=8183892; DOI=10.1073/pnas.91.10.4209;
RA Kirszenbaum M., Moreau P., Gluckman E., Dausset J., Carosella E.;
RT "An alternatively spliced form of HLA-G mRNA in human trophoblasts and
RT evidence for the presence of HLA-G transcript in adult lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:4209-4213(1994).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 5), AND SUBCELLULAR LOCATION (ISOFORM 5).
RX PubMed=7558941; DOI=10.1016/0198-8859(95)00009-s;
RA Moreau P., Carosella E., Teyssier M., Prost S., Gluckman E., Dausset J.,
RA Kirszenbaum M.;
RT "Soluble HLA-G molecule. An alternatively spliced HLA-G mRNA form candidate
RT to encode it in peripheral blood mononuclear cells and human
RT trophoblasts.";
RL Hum. Immunol. 43:231-236(1995).
RN [11]
RP ALTERNATIVE SPLICING (ISOFORM 7), SUBCELLULAR LOCATION (ISOFORM 5), TISSUE
RP SPECIFICITY (ISOFORMS 5 AND 7), AND DEVELOPMENTAL STAGE (ISOFORM 7).
RX PubMed=11137219; DOI=10.1016/s0198-8859(00)00197-x;
RA Paul P., Cabestre F.A., Ibrahim E.C., Lefebvre S., Khalil-Daher I.,
RA Vazeux G., Quiles R.M., Bermond F., Dausset J., Carosella E.D.;
RT "Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and
RT expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected
RT cells.";
RL Hum. Immunol. 61:1138-1149(2000).
RN [12]
RP FUNCTION (ISOFORMS 1 AND 5), SUBUNIT (ISOFORMS 1 AND 5), INTERACTION WITH
RP SELF-PEPTIDE (ISOFORMS 1 AND 5), AND SUBCELLULAR LOCATION (ISOFORMS 1 AND
RP 5).
RX PubMed=7584149; DOI=10.1016/1074-7613(95)90130-2;
RA Lee N., Malacko A.R., Ishitani A., Chen M.C., Bajorath J., Marquardt H.,
RA Geraghty D.E.;
RT "The membrane-bound and soluble forms of HLA-G bind identical sets of
RT endogenous peptides but differ with respect to TAP association.";
RL Immunity 3:591-600(1995).
RN [13]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH SELF-PEPTIDE.
RX PubMed=8805247; DOI=10.1016/s0960-9822(02)00481-5;
RA Diehl M., Muenz C., Keilholz W., Stevanovic S., Holmes N., Loke Y.W.,
RA Rammensee H.G.;
RT "Nonclassical HLA-G molecules are classical peptide presenters.";
RL Curr. Biol. 6:305-314(1996).
RN [14]
RP SUBUNIT, AND INTERACTION WITH CALR.
RX PubMed=9640257; DOI=10.1046/j.1365-2567.1998.00439.x;
RA Wainwright S.D., Simpson K.L., Holmes C.H.;
RT "Calreticulin associates with non-HLA-A,-B class I proteins in the human
RT choriocarcinoma cell lines JEG-3 and BeWo.";
RL Immunology 93:437-445(1998).
RN [15]
RP FUNCTION (ISOFORM 1), SUBUNIT (ISOFORM 1), AND INTERACTION WITH KIR2DL4.
RX PubMed=10190900; DOI=10.1084/jem.189.7.1093;
RA Rajagopalan S., Long E.O.;
RT "A human histocompatibility leukocyte antigen (HLA)-G-specific receptor
RT expressed on all natural killer cells.";
RL J. Exp. Med. 189:1093-1100(1999).
RN [16]
RP MUTAGENESIS OF 334-LYS-LYS-335, SUBUNIT, INTERACTION WITH COPB1, AND MOTIF.
RX PubMed=11520457; DOI=10.1016/s1074-7613(01)00179-0;
RA Park B., Lee S., Kim E., Chang S., Jin M., Ahn K.;
RT "The truncated cytoplasmic tail of HLA-G serves a quality-control function
RT in post-ER compartments.";
RL Immunity 15:213-224(2001).
RN [17]
RP FUNCTION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=11290782; DOI=10.4049/jimmunol.166.8.5018;
RA Riteau B., Rouas-Freiss N., Menier C., Paul P., Dausset J., Carosella E.D.;
RT "HLA-G2, -G3, and -G4 isoforms expressed as nonmature cell surface
RT glycoproteins inhibit NK and antigen-specific CTL cytolysis.";
RL J. Immunol. 166:5018-5026(2001).
RN [18]
RP SUBUNIT, MUTAGENESIS OF CYS-66, AND DISULFIDE BOND AT CYS-66.
RX PubMed=12454284; DOI=10.1073/pnas.212643199;
RA Boyson J.E., Erskine R., Whitman M.C., Chiu M., Lau J.M., Koopman L.A.,
RA Valter M.M., Angelisova P., Horejsi V., Strominger J.L.;
RT "Disulfide bond-mediated dimerization of HLA-G on the cell surface.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16180-16185(2002).
RN [19]
RP SUBUNIT, INTERACTION WITH COPB1, AND MUTAGENESIS OF GLU-138.
RX PubMed=12582157; DOI=10.1074/jbc.m212882200;
RA Park B., Ahn K.;
RT "An essential function of tapasin in quality control of HLA-G molecules.";
RL J. Biol. Chem. 278:14337-14345(2003).
RN [20]
RP DISULFIDE BOND, MUTAGENESIS OF CYS-66 AND CYS-171, SUBUNIT, AND INTERACTION
RP WITH LILRB1.
RX PubMed=12874224; DOI=10.4049/jimmunol.171.3.1343;
RA Gonen-Gross T., Achdout H., Gazit R., Hanna J., Mizrahi S., Markel G.,
RA Goldman-Wohl D., Yagel S., Horejsi V., Levy O., Baniyash M., Mandelboim O.;
RT "Complexes of HLA-G protein on the cell surface are important for leukocyte
RT Ig-like receptor-1 function.";
RL J. Immunol. 171:1343-1351(2003).
RN [21]
RP SUBUNIT, INTERACTION WITH LILRB1 AND LILRB2, AND INTERACTION WITH CD8A.
RX PubMed=12853576; DOI=10.1073/pnas.1431057100;
RA Shiroishi M., Tsumoto K., Amano K., Shirakihara Y., Colonna M., Braud V.M.,
RA Allan D.S.J., Makadzange A., Rowland-Jones S., Willcox B.E., Jones E.Y.,
RA van der Merwe P.A., Kumagai I., Maenaka K.;
RT "Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete
RT with CD8 for MHC class I binding and bind preferentially to HLA-G.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8856-8861(2003).
RN [22]
RP FUNCTION (ISOFORM 1), SUBUNIT, AND INTERACTION WITH CD160.
RX PubMed=16809620; DOI=10.1182/blood-2005-12-019919;
RA Fons P., Chabot S., Cartwright J.E., Lenfant F., L'Faqihi F.,
RA Giustiniani J., Herault J.P., Gueguen G., Bono F., Savi P.,
RA Aguerre-Girr M., Fournel S., Malecaze F., Bensussan A., Plouet J.,
RA Le Bouteiller P.;
RT "Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by
RT direct binding to CD160 receptor expressed by endothelial cells.";
RL Blood 108:2608-2615(2006).
RN [23]
RP TISSUE SPECIFICITY, AND INDUCTION BY PROGESTERONE.
RX PubMed=16210391; DOI=10.1093/humrep/dei305;
RA Yie S.M., Li L.H., Li G.M., Xiao R., Librach C.L.;
RT "Progesterone enhances HLA-G gene expression in JEG-3 choriocarcinoma cells
RT and human cytotrophoblasts in vitro.";
RL Hum. Reprod. 21:46-51(2006).
RN [24]
RP FUNCTION (ISOFORMS 1 AND 5), SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION
RP WITH KIR2DL4.
RX PubMed=16366734; DOI=10.1371/journal.pbio.0040009;
RA Rajagopalan S., Bryceson Y.T., Kuppusamy S.P., Geraghty D.E.,
RA van der Meer A., Joosten I., Long E.O.;
RT "Activation of NK cells by an endocytosed receptor for soluble HLA-G.";
RL PLoS Biol. 4:E9-E9(2006).
RN [25]
RP FUNCTION (ISOFORMS 1 AND 5).
RX PubMed=19304799; DOI=10.1073/pnas.0901173106;
RA Li C., Houser B.L., Nicotra M.L., Strominger J.L.;
RT "HLA-G homodimer-induced cytokine secretion through HLA-G receptors on
RT human decidual macrophages and natural killer cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5767-5772(2009).
RN [26]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION BY IL10.
RX PubMed=20448110; DOI=10.1182/blood-2009-07-234872;
RA Gregori S., Tomasoni D., Pacciani V., Scirpoli M., Battaglia M.,
RA Magnani C.F., Hauben E., Roncarolo M.G.;
RT "Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10
RT requires the IL-10-dependent ILT4/HLA-G pathway.";
RL Blood 116:935-944(2010).
RN [27]
RP FUNCTION.
RX PubMed=20179272; DOI=10.1126/scisignal.2000467;
RA Rajagopalan S., Moyle M.W., Joosten I., Long E.O.;
RT "DNA-PKcs controls an endosomal signaling pathway for a proinflammatory
RT response by natural killer cells.";
RL Sci. Signal. 3:RA14-RA14(2010).
RN [28]
RP FUNCTION.
RX PubMed=23184984; DOI=10.1073/pnas.1208248109;
RA Rajagopalan S., Long E.O.;
RT "Cellular senescence induced by CD158d reprograms natural killer cells to
RT promote vascular remodeling.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:20596-20601(2012).
RN [29]
RP PROTEOLYTIC PROCESSING (ISOFORM 1), AND SUBCELLULAR LOCATION (ISOFORM 1).
RX PubMed=23737137; DOI=10.1007/s11010-013-1708-5;
RA Rizzo R., Trentini A., Bortolotti D., Manfrinato M.C., Rotola A.,
RA Castellazzi M., Melchiorri L., Di Luca D., Dallocchio F., Fainardi E.,
RA Bellini T.;
RT "Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell
RT surface proteolytic shedding.";
RL Mol. Cell. Biochem. 381:243-255(2013).
RN [30]
RP FUNCTION (ISOFORMS 1 AND 5), AND TISSUE SPECIFICITY.
RX PubMed=24453251; DOI=10.4049/jimmunol.1300438;
RA Naji A., Menier C., Morandi F., Agaugue S., Maki G., Ferretti E., Bruel S.,
RA Pistoia V., Carosella E.D., Rouas-Freiss N.;
RT "Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses
RT B cell responses.";
RL J. Immunol. 192:1536-1546(2014).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=26460007; DOI=10.1073/pnas.1517724112;
RA Tilburgs T., Evans J.H., Crespo A.C., Strominger J.L.;
RT "The HLA-G cycle provides for both NK tolerance and immunity at the
RT maternal-fetal interface.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:13312-13317(2015).
RN [32]
RP FUNCTION (ISOFORM 1).
RX PubMed=27859042; DOI=10.1002/eji.201646564;
RA Koestlin N., Ostermeir A.L., Spring B., Schwarz J., Marme A., Walter C.B.,
RA Poets C.F., Gille C.;
RT "HLA-G promotes myeloid-derived suppressor cell accumulation and
RT suppressive activity during human pregnancy through engagement of the
RT receptor ILT4.";
RL Eur. J. Immunol. 47:374-384(2017).
RN [33]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=29262349; DOI=10.1016/j.immuni.2017.11.018;
RA Fu B., Zhou Y., Ni X., Tong X., Xu X., Dong Z., Sun R., Tian Z., Wei H.;
RT "Natural Killer Cells Promote Fetal Development through the Secretion of
RT Growth-Promoting Factors.";
RL Immunity 47:1100-1113(2017).
RN [34]
RP SUBUNIT (ISOFORM 2), INTERACTION WITH LILRB2 (ISOFORM 2), AND MUTAGENESIS
RP OF CYS-66.
RX PubMed=28348268; DOI=10.4049/jimmunol.1601296;
RA Kuroki K., Mio K., Takahashi A., Matsubara H., Kasai Y., Manaka S.,
RA Kikkawa M., Hamada D., Sato C., Maenaka K.;
RT "Class II-like structural features and strong receptor binding of the
RT nonclassical HLA-G2 isoform homodimer.";
RL J. Immunol. 198:3399-3403(2017).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 26-300 IN COMPLEX WITH
RP SELF-PEPTIDE, AND DISULFIDE BOND.
RX PubMed=15718280; DOI=10.1073/pnas.0409676102;
RA Clements C.S., Kjer-Nielsen L., Kostenko L., Hoare H.L., Dunstone M.A.,
RA Moses E., Freed K., Brooks A.G., Rossjohn J., McCluskey J.;
RT "Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed
RT at the fetal-maternal interface.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:3360-3365(2005).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 25-300 IN COMPLEX WITH
RP SELF-PEPTIDE, DISULFIDE BOND, AND INTERACTION WITH LILRB1 AND LILRB2.
RX PubMed=16455647; DOI=10.1074/jbc.m512305200;
RA Shiroishi M., Kuroki K., Ose T., Rasubala L., Shiratori I., Arase H.,
RA Tsumoto K., Kumagai I., Kohda D., Maenaka K.;
RT "Efficient leukocyte Ig-like receptor signaling and crystal structure of
RT disulfide-linked HLA-G dimer.";
RL J. Biol. Chem. 281:10439-10447(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 25-300 IN COMPLEX WITH
RP SELF-PEPTIDE, DISULFIDE BOND, AND INTERACTION WITH LILRB1 AND LILRB2.
RX PubMed=17056715; DOI=10.1073/pnas.0605228103;
RA Shiroishi M., Kuroki K., Rasubala L., Tsumoto K., Kumagai I., Kurimoto E.,
RA Kato K., Kohda D., Maenaka K.;
RT "Structural basis for recognition of the nonclassical MHC molecule HLA-G by
RT the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d).";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16412-16417(2006).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 26-298 IN COMPLEX WITH
RP SELF-PEPTIDE, DISULFIDE BOND, AND SUBUNIT.
RX PubMed=20122941; DOI=10.1016/j.jmb.2010.01.052;
RA Walpole N.G., Kjer-Nielsen L., Kostenko L., McCluskey J., Brooks A.G.,
RA Rossjohn J., Clements C.S.;
RT "The structure and stability of the monomorphic HLA-G are influenced by the
RT nature of the bound peptide.";
RL J. Mol. Biol. 397:467-480(2010).
CC -!- FUNCTION: [Isoform 1]: Non-classical major histocompatibility class Ib
CC molecule involved in immune regulatory processes at the maternal-fetal
CC interface (PubMed:23184984, PubMed:29262349, PubMed:19304799). In
CC complex with B2M/beta-2 microglobulin binds a limited repertoire of
CC nonamer self-peptides derived from intracellular proteins including
CC histones and ribosomal proteins (PubMed:7584149, PubMed:8805247).
CC Peptide-bound HLA-G-B2M complex acts as a ligand for
CC inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine
CC immune cells to promote fetal development while maintaining maternal-
CC fetal tolerance (PubMed:23184984, PubMed:29262349, PubMed:16366734,
CC PubMed:19304799, PubMed:20448110, PubMed:27859042). Upon interaction
CC with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK
CC cell senescence-associated secretory phenotype as a molecular switch to
CC promote vascular remodeling and fetal growth in early pregnancy
CC (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799).
CC Through interaction with KIR2DL4 receptor on decidual macrophages
CC induces pro-inflammatory cytokine production mainly associated with
CC tissue remodeling (PubMed:19304799). Through interaction with LILRB2
CC receptor triggers differentiation of type 1 regulatory T cells and
CC myeloid-derived suppressor cells, both of which actively maintain
CC maternal-fetal tolerance (PubMed:20448110, PubMed:27859042). May play a
CC role in balancing tolerance and antiviral-immunity at maternal-fetal
CC interface by keeping in check the effector functions of NK, CD8+ T
CC cells and B cells (PubMed:10190900, PubMed:11290782, PubMed:24453251).
CC Reprograms B cells toward an immune suppressive phenotype via LILRB1
CC (PubMed:24453251). May induce immune activation/suppression via
CC intercellular membrane transfer (trogocytosis), likely enabling
CC interaction with KIR2DL4, which resides mostly in endosomes
CC (PubMed:20179272, PubMed:26460007). Through interaction with the
CC inhibitory receptor CD160 on endothelial cells may control angiogenesis
CC in immune privileged sites (PubMed:16809620).
CC {ECO:0000269|PubMed:10190900, ECO:0000269|PubMed:11290782,
CC ECO:0000269|PubMed:16366734, ECO:0000269|PubMed:16809620,
CC ECO:0000269|PubMed:19304799, ECO:0000269|PubMed:20179272,
CC ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:23184984,
CC ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:26460007,
CC ECO:0000269|PubMed:27859042, ECO:0000269|PubMed:29262349,
CC ECO:0000269|PubMed:7584149, ECO:0000269|PubMed:8805247}.
CC -!- FUNCTION: [Isoform 2]: Likely does not bind B2M and presents peptides.
CC Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity
CC (PubMed:11290782). {ECO:0000269|PubMed:11290782, ECO:0000305}.
CC -!- FUNCTION: [Isoform 3]: Likely does not bind B2M and presents peptides.
CC Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity
CC (PubMed:11290782). {ECO:0000269|PubMed:11290782, ECO:0000305}.
CC -!- FUNCTION: [Isoform 4]: Likely does not bind B2M and presents peptides.
CC Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity
CC (PubMed:11290782). {ECO:0000269|PubMed:11290782, ECO:0000305}.
CC -!- FUNCTION: [Isoform 5]: Non-classical major histocompatibility class Ib
CC molecule involved in immune regulatory processes at the maternal-fetal
CC interface (PubMed:23184984, PubMed:29262349, PubMed:19304799). In
CC complex with B2M/beta-2 microglobulin binds a limited repertoire of
CC nonamer self-peptides derived from intracellular proteins including
CC histones and ribosomal proteins (PubMed:7584149, PubMed:8805247).
CC Peptide-bound HLA-G-B2M complex acts as a ligand for
CC inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine
CC immune cells to promote fetal development while maintaining maternal-
CC fetal tolerance (PubMed:23184984, PubMed:29262349, PubMed:16366734,
CC PubMed:19304799, PubMed:20448110). Upon interaction with KIR2DL4 and
CC LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-
CC associated secretory phenotype as a molecular switch to promote
CC vascular remodeling and fetal growth in early pregnancy
CC (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799).
CC Through interaction with KIR2DL4 receptor on decidual macrophages
CC induces pro-inflammatory cytokine production mainly associated with
CC tissue remodeling (PubMed:19304799). Through interaction with LILRB2
CC receptor triggers differentiation of type 1 regulatory T cells and
CC myeloid-derived suppressor cells, both of which actively maintain
CC maternal-fetal tolerance (PubMed:20448110). Reprograms B cells toward
CC an immune suppressive phenotype via LILRB1 (PubMed:24453251).
CC {ECO:0000269|PubMed:16366734, ECO:0000269|PubMed:19304799,
CC ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:23184984,
CC ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:29262349,
CC ECO:0000269|PubMed:7584149, ECO:0000269|PubMed:8805247}.
CC -!- FUNCTION: [Isoform 6]: Likely does not bind B2M and presents peptides.
CC {ECO:0000305}.
CC -!- FUNCTION: [Isoform 7]: Likely does not bind B2M and presents peptides.
CC {ECO:0000305}.
CC -!- SUBUNIT: Forms a heterotrimer with B2M and a self-peptide (peptide-
CC bound HLA-G-B2M) (PubMed:7584149, PubMed:8805247). HLA-G-B2M complex
CC interacts with components of the antigen processing machinery TAPBP and
CC TAP1-TAP2 complex; this interaction is required for loading of high
CC affinity peptides and heterotrimer translocation to the cell surface
CC (PubMed:7584149). Interacts with CALCR; this interaction is required
CC for appropriate folding (PubMed:9640257). Interacts with COPB1; this
CC interaction mediates the endoplasmic reticulum (ER) retrieval of HLA-G-
CC B2M complexes that bind low affinity peptides (PubMed:11520457,
CC PubMed:12582157). On the cell surface, peptide-bound HLA-G-B2M
CC molecules (referred to as monomers) can form disulfide-linked
CC homomultimers, homodimers and homotrimers (PubMed:12454284,
CC PubMed:12874224, PubMed:16455647). Interacts with KIR2DL4; this
CC interaction is direct (PubMed:10190900, PubMed:16366734). Interacts
CC with LILRB1 and LILRB2 receptors; this interaction is direct
CC (PubMed:16455647, PubMed:16366734, PubMed:17056715, PubMed:12853576).
CC Interacts with CD160; this interactions is direct (PubMed:16809620).
CC Interacts with CD8A homodimer; this interaction is direct and might
CC down-regulate T cell receptor signaling (PubMed:12853576). Isoform 2:
CC Forms a non-disulfide-linked homodimer and interacts with LILRB2
CC (PubMed:28348268). {ECO:0000269|PubMed:10190900,
CC ECO:0000269|PubMed:11520457, ECO:0000269|PubMed:12454284,
CC ECO:0000269|PubMed:12582157, ECO:0000269|PubMed:12853576,
CC ECO:0000269|PubMed:12874224, ECO:0000269|PubMed:16366734,
CC ECO:0000269|PubMed:16455647, ECO:0000269|PubMed:16809620,
CC ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:28348268,
CC ECO:0000269|PubMed:7584149, ECO:0000269|PubMed:8805247,
CC ECO:0000269|PubMed:9640257}.
CC -!- INTERACTION:
CC P17693; P17693: HLA-G; NbExp=5; IntAct=EBI-1043063, EBI-1043063;
CC P17693; Q8NHL6: LILRB1; NbExp=5; IntAct=EBI-1043063, EBI-2805262;
CC P17693; Q8N423: LILRB2; NbExp=7; IntAct=EBI-1043063, EBI-2816428;
CC P17693-2; P17693-2: HLA-G; NbExp=3; IntAct=EBI-16586375, EBI-16586375;
CC P17693-2; Q8N423: LILRB2; NbExp=4; IntAct=EBI-16586375, EBI-2816428;
CC P17693-5; Q8N423: LILRB2; NbExp=2; IntAct=EBI-16586455, EBI-2816428;
CC P17693-6; Q8N423: LILRB2; NbExp=3; IntAct=EBI-16586550, EBI-2816428;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:7584149}; Single-pass
CC type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11520457}. Early endosome membrane
CC {ECO:0000269|PubMed:16366734}.
CC -!- SUBCELLULAR LOCATION: [Soluble HLA class I histocompatibility antigen,
CC alpha chain G]: Secreted {ECO:0000269|PubMed:23737137}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane
CC {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane
CC {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted
CC {ECO:0000269|PubMed:11137219, ECO:0000269|PubMed:7558941,
CC ECO:0000269|PubMed:7584149, ECO:0000269|PubMed:7989753}. Early endosome
CC {ECO:0000269|PubMed:16366734}.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Secreted
CC {ECO:0000269|PubMed:7989753}.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Secreted
CC {ECO:0000269|PubMed:11137219}.
CC -!- SUBCELLULAR LOCATION: Cell projection, filopodium membrane
CC {ECO:0000269|PubMed:26460007}. Note=HLA-G trogocytosis from
CC extravillous trophoblast's filopodia occurs in the majority of decidual
CC NK cells. {ECO:0000269|PubMed:26460007}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=HLA-G1 {ECO:0000303|PubMed:1570318};
CC IsoId=P17693-1; Sequence=Displayed;
CC Name=2; Synonyms=HLA-G2 {ECO:0000303|PubMed:1570318};
CC IsoId=P17693-2; Sequence=VSP_059192, VSP_059195;
CC Name=3; Synonyms=HLA-G3 {ECO:0000303|PubMed:1570318};
CC IsoId=P17693-3; Sequence=VSP_059191;
CC Name=4; Synonyms=HLA-G.3-5 {ECO:0000303|PubMed:8183892}, HLA-G4
CC {ECO:0000303|PubMed:7589701};
CC IsoId=P17693-4; Sequence=VSP_059196;
CC Name=5; Synonyms=HLA-G1sol {ECO:0000303|PubMed:7989753}, HLA-G5
CC {ECO:0000303|PubMed:7558941};
CC IsoId=P17693-5; Sequence=VSP_059197;
CC Name=6; Synonyms=HLA-G2sol {ECO:0000303|PubMed:7989753}, HLA-G6
CC {ECO:0000303|PubMed:11137219};
CC IsoId=P17693-6; Sequence=VSP_059192, VSP_059195, VSP_059197;
CC Name=7; Synonyms=HLA-G7 {ECO:0000303|PubMed:11137219};
CC IsoId=P17693-7; Sequence=VSP_059193, VSP_059194;
CC -!- TISSUE SPECIFICITY: Expressed in adult eye (PubMed:1570318). Expressed
CC in immune cell subsets including monocytes, myeloid and plasmacytoid
CC dendritic cells and regulatory T cells (Tr1)(at protein level)
CC (PubMed:20448110). Secreted by follicular dendritic cell and follicular
CC helper T cells (PubMed:24453251). Isoform 5: Detected in physiological
CC fluids including amniotic fluid and serum (PubMed:11137219). Isoform 7:
CC Expressed in placenta, amniotic membrane, skin cord blood and
CC peripheral blood mononuclear cells (PubMed:11137219).
CC {ECO:0000269|PubMed:11137219, ECO:0000269|PubMed:1570318,
CC ECO:0000269|PubMed:16210391, ECO:0000269|PubMed:20448110,
CC ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:26460007,
CC ECO:0000269|PubMed:7589701}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the morula stage (at protein level)
CC (PubMed:29262349). Expressed in extravillous trophoblast and
CC cytotrophoblast (PubMed:26460007, PubMed:16210391, PubMed:7589701).
CC Expressed in fetal eye and thymus (PubMed:2336406). Isoform 7:
CC Expressed in fetal liver (PubMed:11137219).
CC {ECO:0000269|PubMed:11137219, ECO:0000269|PubMed:2336406,
CC ECO:0000269|PubMed:29262349}.
CC -!- INDUCTION: Up-regulated by immunosuppressive cytokine IL10 on dendritic
CC cells and CD4+ T cells (PubMed:20448110). Up-regulated by progesterone
CC in cytotrophoblasts (PubMed:16210391). {ECO:0000269|PubMed:16210391,
CC ECO:0000269|PubMed:20448110}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11290782}.
CC -!- PTM: [Soluble HLA class I histocompatibility antigen, alpha chain G]:
CC Produced by proteolytic cleavage at the cell surface (shedding) by
CC matrix metalloproteinase MMP2. {ECO:0000269|PubMed:23737137}.
CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HLAGID43744ch6p22.html";
CC ---------------------------------------------------------------------------
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DR EMBL; X17273; CAA35174.1; -; mRNA.
DR EMBL; J03027; AAA98745.1; -; Genomic_DNA.
DR EMBL; M90683; AAA52673.1; -; mRNA.
DR EMBL; AF055066; AAC24826.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63336.1; -; Genomic_DNA.
DR CCDS; CCDS4668.1; -. [P17693-1]
DR PIR; A39953; A39953.
DR RefSeq; NP_002118.1; NM_002127.5. [P17693-1]
DR PDB; 1YDP; X-ray; 1.90 A; A=26-300.
DR PDB; 2D31; X-ray; 3.20 A; A/D=25-300.
DR PDB; 2DYP; X-ray; 2.50 A; A=25-300.
DR PDB; 3BZE; X-ray; 2.50 A; P/Q/R/S=3-11.
DR PDB; 3CDG; X-ray; 3.40 A; P/Q=3-11.
DR PDB; 3CII; X-ray; 4.41 A; C/F=3-11.
DR PDB; 3KYN; X-ray; 2.40 A; A=26-299.
DR PDB; 3KYO; X-ray; 1.70 A; A/C=26-298.
DR PDB; 6AEE; X-ray; 3.30 A; A/D=25-300.
DR PDB; 6K60; X-ray; 3.15 A; A/E=25-300.
DR PDBsum; 1YDP; -.
DR PDBsum; 2D31; -.
DR PDBsum; 2DYP; -.
DR PDBsum; 3BZE; -.
DR PDBsum; 3CDG; -.
DR PDBsum; 3CII; -.
DR PDBsum; 3KYN; -.
DR PDBsum; 3KYO; -.
DR PDBsum; 6AEE; -.
DR PDBsum; 6K60; -.
DR AlphaFoldDB; P17693; -.
DR SMR; P17693; -.
DR BioGRID; 109380; 130.
DR DIP; DIP-46121N; -.
DR IntAct; P17693; 15.
DR MINT; P17693; -.
DR STRING; 9606.ENSP00000412927; -.
DR GlyGen; P17693; 1 site.
DR iPTMnet; P17693; -.
DR PhosphoSitePlus; P17693; -.
DR SwissPalm; P17693; -.
DR BioMuta; HLA-G; -.
DR DMDM; 122132; -.
DR EPD; P17693; -.
DR jPOST; P17693; -.
DR MassIVE; P17693; -.
DR PaxDb; P17693; -.
DR PeptideAtlas; P17693; -.
DR PRIDE; P17693; -.
DR ProteomicsDB; 53506; -.
DR ABCD; P17693; 49 sequenced antibodies.
DR Antibodypedia; 4253; 1476 antibodies from 40 providers.
DR DNASU; 3135; -.
DR Ensembl; ENST00000360323.11; ENSP00000353472.6; ENSG00000204632.13. [P17693-1]
DR Ensembl; ENST00000376815.3; ENSP00000366011.3; ENSG00000204632.13. [P17693-3]
DR Ensembl; ENST00000383621.8; ENSP00000373116.4; ENSG00000206506.10. [P17693-1]
DR Ensembl; ENST00000383622.8; ENSP00000373117.4; ENSG00000206506.10. [P17693-3]
DR Ensembl; ENST00000415687.6; ENSP00000389969.2; ENSG00000237216.8. [P17693-3]
DR Ensembl; ENST00000423011.6; ENSP00000389522.2; ENSG00000233095.8. [P17693-1]
DR Ensembl; ENST00000423373.6; ENSP00000405238.2; ENSG00000235346.9. [P17693-1]
DR Ensembl; ENST00000428952.6; ENSP00000388176.2; ENSG00000235680.8. [P17693-1]
DR Ensembl; ENST00000429890.6; ENSP00000401326.2; ENSG00000235680.8. [P17693-3]
DR Ensembl; ENST00000444098.6; ENSP00000398200.2; ENSG00000230413.9. [P17693-1]
DR Ensembl; ENST00000445373.6; ENSP00000416408.2; ENSG00000230413.9. [P17693-3]
DR Ensembl; ENST00000448306.6; ENSP00000413926.2; ENSG00000233095.8. [P17693-3]
DR Ensembl; ENST00000449127.6; ENSP00000408773.2; ENSG00000237216.8. [P17693-1]
DR Ensembl; ENST00000457132.6; ENSP00000410247.2; ENSG00000235346.9. [P17693-3]
DR Ensembl; ENST00000546545.2; ENSP00000447762.1; ENSG00000230413.9. [P17693-1]
DR Ensembl; ENST00000546634.1; ENSP00000447780.1; ENSG00000235346.9. [P17693-1]
DR Ensembl; ENST00000547241.2; ENSP00000448085.1; ENSG00000233095.8. [P17693-1]
DR Ensembl; ENST00000547931.1; ENSP00000448363.1; ENSG00000237216.8. [P17693-1]
DR Ensembl; ENST00000550897.1; ENSP00000449903.1; ENSG00000235680.8. [P17693-1]
DR Ensembl; ENST00000553052.2; ENSP00000449291.1; ENSG00000206506.10. [P17693-1]
DR Ensembl; ENST00000622601.4; ENSP00000479399.1; ENSG00000276051.4. [P17693-3]
DR GeneID; 3135; -.
DR KEGG; hsa:3135; -.
DR MANE-Select; ENST00000360323.11; ENSP00000353472.6; NM_001384290.1; NP_001371219.1.
DR CTD; 3135; -.
DR DisGeNET; 3135; -.
DR GeneCards; HLA-G; -.
DR HGNC; HGNC:4964; HLA-G.
DR HPA; ENSG00000204632; Group enriched (pituitary gland, placenta).
DR MalaCards; HLA-G; -.
DR MIM; 142871; gene.
DR neXtProt; NX_P17693; -.
DR OpenTargets; ENSG00000204632; -.
DR PharmGKB; PA35083; -.
DR VEuPathDB; HostDB:ENSG00000204632; -.
DR eggNOG; ENOG502RQEK; Eukaryota.
DR GeneTree; ENSGT00980000198488; -.
DR HOGENOM; CLU_047501_1_1_1; -.
DR InParanoid; P17693; -.
DR OMA; HILQGMF; -.
DR PhylomeDB; P17693; -.
DR TreeFam; TF336617; -.
DR PathwayCommons; P17693; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; P17693; -.
DR SIGNOR; P17693; -.
DR BioGRID-ORCS; 3135; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; HLA-G; human.
DR EvolutionaryTrace; P17693; -.
DR GeneWiki; HLA-G; -.
DR GenomeRNAi; 3135; -.
DR Pharos; P17693; Tbio.
DR PRO; PR:P17693; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P17693; protein.
DR Bgee; ENSG00000204632; Expressed in placenta and 92 other tissues.
DR ExpressionAtlas; P17693; baseline and differential.
DR Genevisible; P17693; HS.
DR GO; GO:0033106; C:cis-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; TAS:Reactome.
DR GO; GO:0042610; F:CD8 receptor binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042605; F:peptide antigen binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IDA:UniProtKB.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR GO; GO:0002767; P:immune response-inhibiting cell surface receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:2001199; P:negative regulation of dendritic cell differentiation; IDA:BHF-UCL.
DR GO; GO:0070317; P:negative regulation of G0 to G1 transition; IDA:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; IC:UniProtKB.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0002451; P:peripheral B cell tolerance induction; IDA:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:UniProtKB.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IDA:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:BHF-UCL.
DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; IMP:BHF-UCL.
DR GO; GO:0002645; P:positive regulation of tolerance induction; IMP:UniProtKB.
DR GO; GO:0042270; P:protection from natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR001039; MHC_I_a_a1/a2.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00129; MHC_I; 1.
DR PRINTS; PR01638; MHCCLASSI.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Immunity;
KW Membrane; MHC I; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..24
FT CHAIN 25..338
FT /note="HLA class I histocompatibility antigen, alpha chain
FT G"
FT /id="PRO_0000018886"
FT CHAIN ?..338
FT /note="Soluble HLA class I histocompatibility antigen,
FT alpha chain G"
FT /evidence="ECO:0000269|PubMed:23737137"
FT /id="PRO_0000445908"
FT TOPO_DOM 25..308
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 209..299
FT /note="Ig-like C1-type"
FT REGION 25..114
FT /note="Alpha-1"
FT REGION 115..206
FT /note="Alpha-2"
FT REGION 207..298
FT /note="Alpha-3"
FT REGION 299..308
FT /note="Connecting peptide"
FT MOTIF 334..336
FT /note="ER-retrieval signal"
FT /evidence="ECO:0000269|PubMed:11520457"
FT BINDING 31
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:20122941"
FT BINDING 94
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280"
FT BINDING 101
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:16455647"
FT BINDING 108
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:16455647, ECO:0000269|PubMed:20122941"
FT BINDING 167
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:20122941"
FT BINDING 170
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:20122941"
FT BINDING 179
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:20122941"
FT BINDING 180
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:17056715"
FT BINDING 183
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:20122941"
FT BINDING 195
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:15718280,
FT ECO:0000269|PubMed:16455647, ECO:0000269|PubMed:17056715,
FT ECO:0000269|PubMed:20122941"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 66
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:12454284, ECO:0000269|PubMed:12874224"
FT DISULFID 125..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:15718280, ECO:0000269|PubMed:16455647,
FT ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:20122941"
FT DISULFID 171
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:12874224"
FT DISULFID 227..283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:15718280, ECO:0000269|PubMed:16455647,
FT ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:20122941"
FT VAR_SEQ 115..298
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000269|PubMed:1570318"
FT /id="VSP_059191"
FT VAR_SEQ 115..206
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000269|PubMed:1570318"
FT /id="VSP_059192"
FT VAR_SEQ 116
FT /note="S -> E (in isoform 7)"
FT /evidence="ECO:0000269|PubMed:11137219"
FT /id="VSP_059193"
FT VAR_SEQ 117..338
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000269|PubMed:11137219"
FT /id="VSP_059194"
FT VAR_SEQ 207..298
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000269|PubMed:7589701,
FT ECO:0000269|PubMed:8183892"
FT /id="VSP_059196"
FT VAR_SEQ 207
FT /note="D -> K (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000269|PubMed:1570318"
FT /id="VSP_059195"
FT VAR_SEQ 299..338
FT /note="KQSSLPTIPIMGIVAGLVVLAAVVTGAAVAAVLWRKKSSD -> SKEGDGGI
FT MSVRESRSLSEDL (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000269|PubMed:7989753"
FT /id="VSP_059197"
FT MUTAGEN 66
FT /note="C->S: Abolishes homodimerization and
FT homotrimerization. Decreases functional interaction with
FT LILRB1. Does not affect homodimerization of isoform 2 and
FT its binding to LILRB2."
FT /evidence="ECO:0000269|PubMed:12454284,
FT ECO:0000269|PubMed:12874224, ECO:0000269|PubMed:28348268"
FT MUTAGEN 138
FT /note="E->H: Enables TAPBP-independent transport to the
FT cell surface."
FT /evidence="ECO:0000269|PubMed:12582157"
FT MUTAGEN 138
FT /note="E->Q: Decreases TAPBP-dependent transport to the
FT cell surface."
FT /evidence="ECO:0000269|PubMed:12582157"
FT MUTAGEN 171
FT /note="C->S: Abolishes homodimerization. Decreases
FT functional interaction with LILRB1."
FT /evidence="ECO:0000269|PubMed:12874224"
FT MUTAGEN 334..335
FT /note="KK->AA: Abolishes binding to COPB1 and Golgi-to-ER
FT retrograde transport."
FT /evidence="ECO:0000269|PubMed:11520457"
FT STRAND 27..36
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:2D31"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 81..108
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2DYP"
FT STRAND 118..132
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 134..142
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 162..173
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 187..198
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 210..218
FT /evidence="ECO:0007829|PDB:3KYO"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 222..235
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 238..243
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:1YDP"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 265..274
FT /evidence="ECO:0007829|PDB:3KYO"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 281..286
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:3KYO"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3KYO"
SQ SEQUENCE 338 AA; 38224 MW; 0678E263BE8962FF CRC64;
MVVMAPRTLF LLLSGALTLT ETWAGSHSMR YFSAAVSRPG RGEPRFIAMG YVDDTQFVRF
DSDSACPRME PRAPWVEQEG PEYWEEETRN TKAHAQTDRM NLQTLRGYYN QSEASSHTLQ
WMIGCDLGSD GRLLRGYEQY AYDGKDYLAL NEDLRSWTAA DTAAQISKRK CEAANVAEQR
RAYLEGTCVE WLHRYLENGK EMLQRADPPK THVTHHPVFD YEATLRCWAL GFYPAEIILT
WQRDGEDQTQ DVELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLMLRWKQ
SSLPTIPIMG IVAGLVVLAA VVTGAAVAAV LWRKKSSD
