HLA class II histocompatibility antigen, DQ alpha 2 chain

Details

Name
HLA class II histocompatibility antigen, DQ alpha 2 chain
Synonyms
  • DX alpha chain
  • HLA class II histocompatibility antigen, DQ(6) alpha chain
  • HLA-DQA1
  • HLA-DXA
  • MHC class II DQA2
Gene Name
HLA-DQA2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011537|HLA class II histocompatibility antigen, DQ alpha 2 chain
MILNKALLLGALALTAVMSPCGGEDIVADHVASYGVNFYQSHGPSGQYTHEFDGDEEFYV
DLETKETVWQLPMFSKFISFDPQSALRNMAVGKHTLEFMMRQSNSTAATNEVPEVTVFSK
FPVTLGQPNTLICLVDNIFPPVVNITWLSNGHSVTEGVSETSFLSKSDHSFFKISYLTFL
PSADEIYDCKVEHWGLDEPLLKHWEPEIPAPMSELTETLVCALGLSVGLMGIVVGTVFII
QGLRSVGASRHQGLL
Number of residues
255
Molecular Weight
28032.82
Theoretical pI
4.53
GO Classification
Functions
MHC class II receptor activity
Processes
antigen processing and presentation of exogenous peptide antigen via MHC class II / cytokine-mediated signaling pathway / immune response / interferon-gamma-mediated signaling pathway / T cell costimulation / T cell receptor signaling pathway
Components
clathrin-coated endocytic vesicle membrane / endocytic vesicle membrane / endosome membrane / ER to Golgi transport vesicle membrane / Golgi membrane / integral component of lumenal side of endoplasmic reticulum membrane / integral component of plasma membrane / lysosomal membrane / MHC class II protein complex / plasma membrane / trans-Golgi network membrane / transport vesicle membrane
General Function
Mhc class ii receptor activity
Specific Function
Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
Pfam Domain Function
Transmembrane Regions
218-240
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0011538|HLA class II histocompatibility antigen, DQ alpha 2 chain (HLA-DQA2)
ATGATCCTAAACAAAGCTCTGCTGCTGGGGGCCCTCGCCCTGACTGCCGTGATGAGCCCC
TGTGGAGGTGAAGACATTGTGGCTGACCATGTTGCCTCCTATGGTGTGAACTTCTACCAG
TCTCACGGTCCCTCTGGCCAGTACACCCATGAATTTGATGGAGACGAGGAGTTCTATGTG
GACCTGGAGACGAAAGAGACTGTCTGGCAGTTGCCTATGTTTAGCAAATTTATAAGTTTT
GACCCGCAGAGTGCACTGAGAAATATGGCTGTGGGAAAACACACCTTGGAATTCATGATG
AGACAGTCCAACTCTACCGCTGCCACCAATGAGGTTCCTGAGGTCACAGTGTTTTCCAAG
TTTCCTGTGACGCTGGGTCAGCCCAACACCCTCATCTGTCTTGTGGACAACATCTTTCCT
CCTGTGGTCAACATCACCTGGCTGAGCAATGGGCACTCAGTCACAGAAGGTGTTTCTGAG
ACCAGCTTCCTCTCCAAGAGTGATCATTCCTTCTTCAAGATCAGTTACCTCACCTTCCTC
CCTTCTGCTGATGAGATTTATGACTGCAAGGTGGAGCACTGGGGCCTGGACGAGCCTCTT
CTGAAACACTGGGAGCCTGAGATTCCAGCCCCTATGTCAGAGCTCACAGAGACTTTGGTC
TGCGCCCTGGGGTTGTCTGTGGGCCTCATGGGCATTGTGGTGGGCACTGTCTTCATCATC
CAAGGCCTGCGTTCAGTTGGTGCTTCCAGACACCAAGGGCTCTTATGA
Chromosome Location
6
Locus
6p21.3
External Identifiers
ResourceLink
UniProtKB IDP01906
UniProtKB Entry NameDQA2_HUMAN
GenBank Protein ID493166
GenBank Gene IDM29615
GenAtlas IDHLA-DQA2
HGNC IDHGNC:4943
General References
  1. Jonsson AK, Hyldig-Nielsen JJ, Servenius B, Larhammar D, Andersson G, Jorgensen F, Peterson PA, Rask L: Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes. J Biol Chem. 1987 Jun 25;262(18):8767-77. [PubMed:3036828]
  2. Auffray C, Lillie JW, Arnot D, Grossberger D, Kappes D, Strominger JL: Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes. Nature. 1984 Mar 22-28;308(5957):327-33. [PubMed:6584734]
  3. Auffray C, Lillie JW, Korman AJ, Boss JM, Frechin N, Guillemot F, Cooper J, Mulligan RC, Strominger JL: Structure and expression of HLA-DQ alpha and -DX alpha genes: interallelic alternate splicing of the HLA-DQ alpha gene and functional splicing of the HLA-DQ alpha gene using a retroviral vector. Immunogenetics. 1987;26(1-2):63-73. [PubMed:3610256]
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  5. Rudy G, Lew AM: Limited polymorphism of the HLA-DQA2 promoter and identification of a variant octamer. Hum Immunol. 1994 Mar;39(3):225-9. [PubMed:8026991]
  6. Gyllensten UB, Erlich HA: Ancient roots for polymorphism at the HLA-DQ alpha locus in primates. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9986-90. [PubMed:2513578]
  7. Rudy GB, Lew AM: The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of B lymphoblastoid cells. J Immunol. 1997 Mar 1;158(5):2116-25. [PubMed:9036956]
  8. Cresswell P: Invariant chain structure and MHC class II function. Cell. 1996 Feb 23;84(4):505-7. [PubMed:8598037]
  9. Villadangos JA: Presentation of antigens by MHC class II molecules: getting the most out of them. Mol Immunol. 2001 Sep;38(5):329-46. [PubMed:11684289]
  10. Rocha N, Neefjes J: MHC class II molecules on the move for successful antigen presentation. EMBO J. 2008 Jan 9;27(1):1-5. Epub 2007 Nov 29. [PubMed:18046453]
  11. Menendez-Benito V, Neefjes J: Autophagy in MHC class II presentation: sampling from within. Immunity. 2007 Jan;26(1):1-3. [PubMed:17241953]
  12. Berger AC, Roche PA: MHC class II transport at a glance. J Cell Sci. 2009 Jan 1;122(Pt 1):1-4. doi: 10.1242/jcs.035089. [PubMed:19092054]
  13. Beswick EJ, Reyes VE: CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. World J Gastroenterol. 2009 Jun 21;15(23):2855-61. [PubMed:19533806]
  14. Lenormand C, Bausinger H, Gross F, Signorino-Gelo F, Koch S, Peressin M, Fricker D, Cazenave JP, Bieber T, Hanau D, de la Salle H, Tourne S: HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells and encode a new HLA class II molecule. J Immunol. 2012 Apr 15;188(8):3903-11. doi: 10.4049/jimmunol.1103048. Epub 2012 Mar 9. [PubMed:22407913]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00071Insulin PorkapprovedunknownDetails