ID DQA2_HUMAN Reviewed; 255 AA. AC P01906; A2BF37; B0V0E7; O19789; Q5SQ94; Q5SR04; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 2. DT 13-FEB-2019, entry version 170. DE RecName: Full=HLA class II histocompatibility antigen, DQ alpha 2 chain; DE AltName: Full=DX alpha chain; DE AltName: Full=HLA class II histocompatibility antigen, DQ(6) alpha chain; DE AltName: Full=HLA-DQA1; DE AltName: Full=MHC class II DQA2; DE Flags: Precursor; GN Name=HLA-DQA2; Synonyms=HLA-DXA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3036828; RA Jonsson A.-K., Hyldig-Nielsen J.-J., Servenius B., Larhammar D., RA Andersson G., Joergensen F., Peterson P.A., Rask L.; RT "Class II genes of the human major histocompatibility complex. RT Comparisons of the DQ and DX alpha and beta genes."; RL J. Biol. Chem. 262:8767-8777(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CLONE LAMBDA DCH-10). RX PubMed=6584734; DOI=10.1038/308327a0; RA Auffray C., Lillie J.W., Arnot D., Grossberger D., Kappes D., RA Strominger J.L.; RT "Isotypic and allotypic variation of human class II histocompatibility RT antigen alpha-chain genes."; RL Nature 308:327-333(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3610256; DOI=10.1007/BF00345456; RA Auffray C., Lillie J.W., Korman A.J., Boss J.M., Frechin N., RA Guillemot F., Cooper J., Mulligan R.C., Strominger J.L.; RT "Structure and expression of HLA-DQ alpha and -DX alpha genes: RT interallelic alternate splicing of the HLA-DQ alpha gene and RT functional splicing of the HLA-DQ alpha gene using a retroviral RT vector."; RL Immunogenetics 26:63-73(1987). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ALA-227 RP AND ASP-247. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-13. RX PubMed=8026991; DOI=10.1016/0198-8859(94)90264-X; RA Rudy G., Lew A.M.; RT "Limited polymorphism of the HLA-DQA2 promoter and identification of a RT variant octamer."; RL Hum. Immunol. 39:225-229(1994). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-103. RX PubMed=2513578; DOI=10.1073/pnas.86.24.9986; RA Gyllensten U.B., Erlich H.A.; RT "Ancient roots for polymorphism at the HLA-DQ alpha locus in RT primates."; RL Proc. Natl. Acad. Sci. U.S.A. 86:9986-9990(1989). RN [7] RP TISSUE SPECIFICITY. RX PubMed=9036956; RA Rudy G.B., Lew A.M.; RT "The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on RT the surface of B lymphoblastoid cells."; RL J. Immunol. 158:2116-2125(1997). RN [8] RP REVIEW. RX PubMed=8598037; DOI=10.1016/S0092-8674(00)81025-9; RA Cresswell P.; RT "Invariant chain structure and MHC class II function."; RL Cell 84:505-507(1996). RN [9] RP REVIEW. RX PubMed=11684289; DOI=10.1016/S0161-5890(01)00069-4; RA Villadangos J.A.; RT "Presentation of antigens by MHC class II molecules: getting the most RT out of them."; RL Mol. Immunol. 38:329-346(2001). RN [10] RP REVIEW. RX PubMed=18046453; DOI=10.1038/sj.emboj.7601945; RA Rocha N., Neefjes J.; RT "MHC class II molecules on the move for successful antigen RT presentation."; RL EMBO J. 27:1-5(2008). RN [11] RP REVIEW. RX PubMed=17241953; DOI=10.1016/j.immuni.2007.01.005; RA Menendez-Benito V., Neefjes J.; RT "Autophagy in MHC class II presentation: sampling from within."; RL Immunity 26:1-3(2007). RN [12] RP REVIEW. RX PubMed=19092054; DOI=10.1242/jcs.035089; RA Berger A.C., Roche P.A.; RT "MHC class II transport at a glance."; RL J. Cell Sci. 122:1-4(2009). RN [13] RP REVIEW. RX PubMed=19533806; DOI=10.3748/wjg.15.2855; RA Beswick E.J., Reyes V.E.; RT "CD74 in antigen presentation, inflammation, and cancers of the RT gastrointestinal tract."; RL World J. Gastroenterol. 15:2855-2861(2009). RN [14] RP FUNCTION, INTERACTION WITH CD74; HLA-DMA; HLA-DQB1 AND HLA-DQB2, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=22407913; DOI=10.4049/jimmunol.1103048; RA Lenormand C., Bausinger H., Gross F., Signorino-Gelo F., Koch S., RA Peressin M., Fricker D., Cazenave J.P., Bieber T., Hanau D., RA de la Salle H., Tourne S.; RT "HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human RT Langerhans cells and encode a new HLA class II molecule."; RL J. Immunol. 188:3903-3911(2012). CC -!- FUNCTION: Binds peptides derived from antigens that access the CC endocytic route of antigen presenting cells (APC) and presents CC them on the cell surface for recognition by the CD4 T-cells. The CC peptide binding cleft accommodates peptides of 10-30 residues. The CC peptides presented by MHC class II molecules are generated mostly CC by degradation of proteins that access the endocytic route, where CC they are processed by lysosomal proteases and other hydrolases. CC Exogenous antigens that have been endocytosed by the APC are thus CC readily available for presentation via MHC II molecules, and for CC this reason this antigen presentation pathway is usually referred CC to as exogenous. As membrane proteins on their way to degradation CC in lysosomes as part of their normal turn-over are also contained CC in the endosomal/lysosomal compartments, exogenous antigens must CC compete with those derived from endogenous components. Autophagy CC is also a source of endogenous peptides, autophagosomes CC constitutively fuse with MHC class II loading compartments. In CC addition to APCs, other cells of the gastrointestinal tract, such CC as epithelial cells, express MHC class II molecules and CD74 and CC act as APCs, which is an unusual trait of the GI tract. To produce CC a MHC class II molecule that presents an antigen, three MHC class CC II molecules (heterodimers of an alpha and a beta chain) associate CC with a CD74 trimer in the ER to form a heterononamer. Soon after CC the entry of this complex into the endosomal/lysosomal system CC where antigen processing occurs, CD74 undergoes a sequential CC degradation by various proteases, including CTSS and CTSL, leaving CC a small fragment termed CLIP (class-II-associated invariant chain CC peptide). The removal of CLIP is facilitated by HLA-DM via direct CC binding to the alpha-beta-CLIP complex so that CLIP is released. CC HLA-DM stabilizes MHC class II molecules until primary high CC affinity antigenic peptides are bound. The MHC II molecule bound CC to a peptide is then transported to the cell membrane surface. In CC B-cells, the interaction between HLA-DM and MHC class II molecules CC is regulated by HLA-DO. Primary dendritic cells (DCs) also to CC express HLA-DO. Lysosomal microenvironment has been implicated in CC the regulation of antigen loading into MHC II molecules, increased CC acidification produces increased proteolysis and efficient peptide CC loading. {ECO:0000269|PubMed:22407913}. CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit; also referred CC as MHC class II molecule. Dimer formation with HLA-DQB2, but not CC with HLA-DQB1, is required for efficient exit from the endoplasmic CC reticulum (ER). In the ER, forms a heterononamer; 3 MHC class II CC molecules bind to a CD74 homotrimer (also known as invariant chain CC or HLA class II histocompatibility antigen gamma chain). In the CC endosomal/lysosomal system; CD74 undergoes sequential degradation CC by various proteases; leaving a small fragment termed CLIP on each CC MHC class II molecule. MHC class II molecule interacts with CC HLA_DM, and HLA_DO in B-cells, in order to release CLIP and CC facilitate the binding of antigenic peptides. Association with CC HLA-DMA also occurs in skin Langerhans cells, in post-Golgi CC compartments. {ECO:0000269|PubMed:22407913}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22407913}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:22407913}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:22407913}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:22407913}. CC Golgi apparatus, trans-Golgi network membrane CC {ECO:0000269|PubMed:22407913}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:22407913}. Endosome membrane CC {ECO:0000269|PubMed:22407913}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:22407913}. Lysosome membrane CC {ECO:0000269|PubMed:22407913}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:22407913}. Note=The MHC class II complex CC transits through a number of intracellular compartments in the CC endocytic pathway until it reaches the cell membrane for antigen CC presentation. CC -!- TISSUE SPECIFICITY: Restricted to skin Langerhans cells, although CC some expression at low levels may occur at the surface of B CC lymphoblastoid cells. {ECO:0000269|PubMed:22407913, CC ECO:0000269|PubMed:9036956}. CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; M29615; AAA59834.1; -; Genomic_DNA. DR EMBL; M29614; AAA59834.1; JOINED; Genomic_DNA. DR EMBL; X00453; CAA25142.1; -; Genomic_DNA. DR EMBL; X00454; CAA25142.1; JOINED; Genomic_DNA. DR EMBL; X00455; CAA25142.1; JOINED; Genomic_DNA. DR EMBL; X00456; CAA25142.1; JOINED; Genomic_DNA. DR EMBL; M17237; AAA59605.1; -; Genomic_DNA. DR EMBL; M17235; AAA59605.1; JOINED; Genomic_DNA. DR EMBL; CR759848; CAQ07531.1; -; Genomic_DNA. DR EMBL; AL773543; CAI18490.1; -; Genomic_DNA. DR EMBL; BX248406; CAM26195.1; -; Genomic_DNA. DR EMBL; BX927131; CAM26195.1; JOINED; Genomic_DNA. DR EMBL; BX927131; CAM26196.1; -; Genomic_DNA. DR EMBL; BX248406; CAM26196.1; JOINED; Genomic_DNA. DR EMBL; AL713890; CAI17623.1; -; Genomic_DNA. DR EMBL; AL672104; CAI18437.1; -; Genomic_DNA. DR EMBL; CR936921; CAQ07312.1; -; Genomic_DNA. DR EMBL; CR753846; CAQ09761.1; -; Genomic_DNA. DR EMBL; BX927160; CAQ10975.1; -; Genomic_DNA. DR EMBL; BX927168; CAQ10975.1; JOINED; Genomic_DNA. DR EMBL; BX927168; CAQ08754.1; -; Genomic_DNA. DR EMBL; BX927160; CAQ08754.1; JOINED; Genomic_DNA. DR EMBL; S71248; AAD14077.1; -; Genomic_DNA. DR CCDS; CCDS4753.1; -. DR PIR; A02210; HLHUDX. DR PIR; I54439; I54439. DR RefSeq; NP_064440.1; NM_020056.4. DR UniGene; Hs.591798; -. DR ProteinModelPortal; P01906; -. DR SMR; P01906; -. DR IntAct; P01906; 1. DR STRING; 9606.ENSP00000364076; -. DR DrugBank; DB00071; Insulin Pork. DR iPTMnet; P01906; -. DR PhosphoSitePlus; P01906; -. DR BioMuta; HLA-DQA2; -. DR DMDM; 122192; -. DR jPOST; P01906; -. DR PaxDb; P01906; -. DR PeptideAtlas; P01906; -. DR PRIDE; P01906; -. DR ProteomicsDB; 51509; -. DR Ensembl; ENST00000241802; ENSP00000241802; ENSG00000206301. DR Ensembl; ENST00000374940; ENSP00000364076; ENSG00000237541. DR Ensembl; ENST00000415898; ENSP00000400695; ENSG00000231526. DR Ensembl; ENST00000443184; ENSP00000405833; ENSG00000257473. DR Ensembl; ENST00000446482; ENSP00000390725; ENSG00000225103. DR Ensembl; ENST00000447735; ENSP00000393431; ENSG00000223793. DR Ensembl; ENST00000449560; ENSP00000401098; ENSG00000233192. DR Ensembl; ENST00000453672; ENSP00000387768; ENSG00000231823. DR Ensembl; ENST00000546801; ENSP00000447668; ENSG00000233192. DR Ensembl; ENST00000551533; ENSP00000448003; ENSG00000223793. DR GeneID; 3118; -. DR KEGG; hsa:3118; -. DR UCSC; uc003obx.4; human. DR CTD; 3118; -. DR DisGeNET; 3118; -. DR EuPathDB; HostDB:ENSG00000237541.3; -. DR GeneCards; HLA-DQA2; -. DR H-InvDB; HIX0058177; -. DR H-InvDB; HIX0166445; -. DR H-InvDB; HIX0166701; -. DR HGNC; HGNC:4943; HLA-DQA2. DR MIM; 613503; gene. DR neXtProt; NX_P01906; -. DR OpenTargets; ENSG00000237541; -. DR PharmGKB; PA35067; -. DR eggNOG; ENOG410IZMF; Eukaryota. DR eggNOG; ENOG410YHX9; LUCA. DR GeneTree; ENSGT00940000162892; -. DR HOGENOM; HOG000112076; -. DR InParanoid; P01906; -. DR KO; K06752; -. DR OMA; LKHWEPD; -. DR OrthoDB; 1132781at2759; -. DR PhylomeDB; P01906; -. DR TreeFam; TF333797; -. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains. DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse. DR Reactome; R-HSA-202433; Generation of second messenger molecules. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR Reactome; R-HSA-389948; PD-1 signaling. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR SIGNOR; P01906; -. DR GeneWiki; HLA-DQA2; -. DR GenomeRNAi; 3118; -. DR PRO; PR:P01906; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000237541; Expressed in 89 organ(s), highest expression level in lung. DR ExpressionAtlas; P01906; baseline and differential. DR Genevisible; P01906; HS. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome. 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:0005887; C:integral component of plasma membrane; NAS:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0042613; C:MHC class II protein complex; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome. DR GO; GO:0030658; C:transport vesicle membrane; TAS:Reactome. DR GO; GO:0032395; F:MHC class II receptor activity; NAS:UniProtKB. DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR Gene3D; 2.60.40.10; -; 1. DR Gene3D; 3.10.320.10; -; 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; IPR011162; MHC_I/II-like_Ag-recog. DR InterPro; IPR014745; MHC_II_a/b_N. DR InterPro; IPR001003; MHC_II_a_N. DR Pfam; PF07654; C1-set; 1. DR Pfam; PF00993; MHC_II_alpha; 1. DR SMART; SM00407; IGc1; 1. DR SMART; SM00920; MHC_II_alpha; 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 Cell membrane; Complete proteome; Disulfide bond; KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; KW Immunity; Lysosome; Membrane; MHC II; Polymorphism; KW Reference proteome; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 23 FT CHAIN 24 255 HLA class II histocompatibility antigen, FT DQ alpha 2 chain. FT /FTId=PRO_0000018973. FT TOPO_DOM 24 217 Extracellular. {ECO:0000255}. FT TRANSMEM 218 240 Helical. {ECO:0000255}. FT TOPO_DOM 241 255 Cytoplasmic. {ECO:0000255}. FT DOMAIN 113 205 Ig-like C1-type. FT REGION 24 110 Alpha-1. FT REGION 111 204 Alpha-2. FT REGION 205 217 Connecting peptide. FT CARBOHYD 104 104 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 144 144 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 133 189 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VARIANT 227 227 V -> A (in dbSNP:rs9276436). FT {ECO:0000269|PubMed:14574404}. FT /FTId=VAR_033431. FT VARIANT 247 247 G -> D (in dbSNP:rs2071800). FT {ECO:0000269|PubMed:14574404}. FT /FTId=VAR_050392. FT CONFLICT 84 84 S -> T (in Ref. 1; AAA59834). FT {ECO:0000305}. FT CONFLICT 101 101 R -> G (in Ref. 4; CAM26196/CAM26195). FT {ECO:0000305}. SQ SEQUENCE 255 AA; 28033 MW; 85B13D9FDF2905FE CRC64; MILNKALLLG ALALTAVMSP CGGEDIVADH VASYGVNFYQ SHGPSGQYTH EFDGDEEFYV DLETKETVWQ LPMFSKFISF DPQSALRNMA VGKHTLEFMM RQSNSTAATN EVPEVTVFSK FPVTLGQPNT LICLVDNIFP PVVNITWLSN GHSVTEGVSE TSFLSKSDHS FFKISYLTFL PSADEIYDCK VEHWGLDEPL LKHWEPEIPA PMSELTETLV CALGLSVGLM GIVVGTVFII QGLRSVGASR HQGLL //