HLA class II histocompatibility antigen, DR alpha chain

NameHLA class II histocompatibility antigen, DR alpha chain
SynonymsHLA-DRA1 MHC class II antigen DRA
Gene NameHLA-DRA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009228|HLA class II histocompatibility antigen, DR alpha chain
MAISGVPVLGFFIIAVLMSAQESWAIKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVD
MAKKETVWRLEEFGRFASFEAQGALANIAVDKANLEIMTKRSNYTPITNVPPEVTVLTNS
PVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLP
STEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIK
GVRKSNAAERRGPL
Number of residues254
Molecular Weight28606.685
Theoretical pINone
GO Classification
Functions
    MHC class II receptor activity
peptide antigen binding
MHC class II protein complex binding
Processes
    T cell receptor signaling pathway
viral process
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
peptide antigen assembly with MHC class II protein complex
interferon-gamma-mediated signaling pathway
polysaccharide assembly with MHC class II protein complex
antigen processing and presentation of exogenous peptide antigen via MHC class II
cognition
cytokine-mediated signaling pathway
immune response
T cell costimulation
Components
    trans-Golgi network membrane
cell surface
extracellular exosome
integral component of plasma membrane
Golgi membrane
transport vesicle membrane
ER to Golgi transport vesicle membrane
late endosome membrane
clathrin-coated endocytic vesicle membrane
endocytic vesicle membrane
integral component of lumenal side of endoplasmic reticulum membrane
plasma membrane
lysosomal membrane
MHC class II protein complex
lysosome
General FunctionPeptide antigen binding
Specific FunctionBinds 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.
Transmembrane Regions217-239
GenBank Protein ID
UniProtKB IDP01903
UniProtKB Entry NameDRA_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0013684|HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)
ATGGCCATAAGTGGAGTCCCTGTGCTAGGATTTTTCATCATAGCTGTGCTGATGAGCGCT
CAGGAATCATGGGCTATCAAAGAAGAACATGTGATCATCCAGGCCGAGTTCTATCTGAAT
CCTGACCAATCAGGCGAGTTTATGTTTGACTTTGATGGTGATGAGATTTTCCATGTGGAT
ATGGCAAAGAAGGAGACGGTCTGGCGGCTTGAAGAATTTGGACGATTTGCCAGCTTTGAG
GCTCAAGGTGCATTGGCCAACATAGCTGTGGACAAAGCCAACCTGGAAATCATGACAAAG
CGCTCCAACTATACTCCGATCACCAATGTACCTCCAGAGGTAACTGTGCTCACAAACAGC
CCTGTGGAACTGAGAGAGCCCAACGTCCTCATCTGTTTCATAGACAAGTTCACCCCACCA
GTGGTCAATGTCACGTGGCTTCGAAATGGAAAACCTGTCACCACAGGAGTGTCAGAGACA
GTCTTCCTGCCCAGGGAAGACCACCTTTTCCGCAAGTTCCACTATCTCCCCTTCCTGCCC
TCAACTGAGGACGTTTACGACTGCAGGGTGGAGCACTGGGGCTTGGATGAGCCTCTTCTC
AAGCACTGGGAGTTTGATGCTCCAAGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGT
GCCCTGGGCCTGACTGTGGGTCTGGTGGGCATCATTATTGGGACCATCTTCATCATCAAG
GGATTGCGCAAAAGCAATGCAGCAGAACGCAGGGGGCCTCTGTAA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:4947
Chromosome Location6
LocusNone
References
  1. Villadangos JA: Presentation of antigens by MHC class II molecules: getting the most out of them. Mol Immunol. 2001 Sep;38(5):329-46.[11684289 ]
  2. 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.[18046453 ]
  3. Menendez-Benito V, Neefjes J: Autophagy in MHC class II presentation: sampling from within. Immunity. 2007 Jan;26(1):1-3.[17241953 ]
  4. De Gassart A, Camosseto V, Thibodeau J, Ceppi M, Catalan N, Pierre P, Gatti E: MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3491-6. doi: 10.1073/pnas.0708874105. Epub 2008 Feb 27.[18305173 ]
  5. 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.[19092054 ]
  6. 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.[19533806 ]
  7. Lapaque N, Jahnke M, Trowsdale J, Kelly AP: The HLA-DRalpha chain is modified by polyubiquitination. J Biol Chem. 2009 Mar 13;284(11):7007-16. doi: 10.1074/jbc.M805736200. Epub 2008 Dec 31.[19117940 ]
  8. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012.[19159218 ]
  9. Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC: Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993 Jul 1;364(6432):33-9.[8316295 ]
  10. Lee JS, Trowsdale J, Travers PJ, Carey J, Grosveld F, Jenkins J, Bodmer WF: Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization of the corresponding gene. Nature. 1982 Oct 21;299(5885):750-2.[6811954 ]
  11. Kajimura Y, Toyoda H, Sato M, Miyakoshi S, Kaplan SA, Ike Y, Goyert SM, Silver J, Hawke D, Shively JE, et al.: Cloning the heavy chain of human HLA-DR antigen using synthetic oligodeoxyribonucleotides as hybridization probes. DNA. 1983;2(3):175-82.[6416803 ]
  12. Schamboeck A, Korman AJ, Kamb A, Strominger JL: Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. Nucleic Acids Res. 1983 Dec 20;11(24):8663-75.[6324094 ]
  13. Das HK, Lawrance SK, Weissman SM: Structure and nucleotide sequence of the heavy chain gene of HLA-DR. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3543-7.[6304715 ]
  14. Koppelman B, Cresswell P: Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. J Immunol. 1990 Oct 15;145(8):2730-6.[2212658 ]
  15. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7.[15489334 ]
  16. Yang C, Kratzin H, Gotz H, Thinnes FP, Kruse T, Egert G, Pauly E, Kolbel S, Wernet P, Hilschmann N: [Primary structure of class II human histocompatibility antigens. 2nd Communication. Amino acid sequence of the N-terminal 179 residues of the alpha-chain of an HLA-Dw2/DR2 alloantigen (author's transl)]. Hoppe Seylers Z Physiol Chem. 1982 Jun;363(6):671-6.[6955253 ]
  17. Walker LE, Hewick R, Hunkapiller MW, Hood LE, Dreyer WJ, Reisfeld RA: N-terminal amino acid sequences of the alpha and beta chains of HLA-DR1 and HLA-DR2 antigens. Biochemistry. 1983 Jan 4;22(1):185-8.[6600932 ]
  18. Larhammar D, Gustafsson K, Claesson L, Bill P, Wiman K, Schenning L, Sundelin J, Widmark E, Peterson PA, Rask L: Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins. Cell. 1982 Aug;30(1):153-61.[6812963 ]
  19. Korman AJ, Auffray C, Schamboeck A, Strominger JL: The amino acid sequence and gene organization of the heavy chain of the HLA-DR antigen: homology to immunoglobulins. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6013-7.[6821129 ]
  20. Kralovicova J, Marsh SG, Waller MJ, Hammarstrom L, Vorechovsky I: The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes. Tissue Antigens. 2002 Sep;60(3):266-7.[12445311 ]
  21. Thursz MR, Thomas HC, Greenwood BM, Hill AV: Heterozygote advantage for HLA class-II type in hepatitis B virus infection. Nat Genet. 1997 Sep;17(1):11-2.[9288086 ]
  22. Cresswell P: Invariant chain structure and MHC class II function. Cell. 1996 Feb 23;84(4):505-7.[8598037 ]
  23. Jardetzky TS, Brown JH, Gorga JC, Stern LJ, Urban RG, Chi YI, Stauffacher C, Strominger JL, Wiley DC: Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature. 1994 Apr 21;368(6473):711-8.[8152483 ]
  24. Ghosh P, Amaya M, Mellins E, Wiley DC: The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature. 1995 Nov 30;378(6556):457-62.[7477400 ]
  25. Dessen A, Lawrence CM, Cupo S, Zaller DM, Wiley DC: X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity. 1997 Oct;7(4):473-81.[9354468 ]
  26. Smith KJ, Pyrdol J, Gauthier L, Wiley DC, Wucherpfennig KW: Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J Exp Med. 1998 Oct 19;188(8):1511-20.[9782128 ]
  27. Li Y, Li H, Dimasi N, McCormick JK, Martin R, Schuck P, Schlievert PM, Mariuzza RA: Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity. 2001 Jan;14(1):93-104.[11163233 ]
  28. Mullen MM, Haan KM, Longnecker R, Jardetzky TS: Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1. Mol Cell. 2002 Feb;9(2):375-85.[11864610 ]
  29. Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, Jones EY, Fugger L: A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol. 2002 Oct;3(10):940-3. Epub 2002 Sep 3.[12244309 ]
  30. Li Y, Huang Y, Lue J, Quandt JA, Martin R, Mariuzza RA: Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J. 2005 Sep 7;24(17):2968-79. Epub 2005 Aug 4.[16079912 ]
  31. Parry CS, Gorski J, Stern LJ: Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity. J Mol Biol. 2007 Aug 10;371(2):435-46. Epub 2007 May 18.[17583734 ]
  32. Dai S, Crawford F, Marrack P, Kappler JW: The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11893-7. doi: 10.1073/pnas.0805810105. Epub 2008 Aug 12.[18697946 ]
  33. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11.[14574404 ]
  34. Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC: Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature. 1994 Mar 17;368(6468):215-21.[8145819 ]
  35. Li Y, Li H, Martin R, Mariuzza RA: Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins. J Mol Biol. 2000 Nov 24;304(2):177-88.[11080454 ]

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