NameHLA class II histocompatibility antigen, DP alpha 1 chain
Synonyms
  • DP(W3)
  • DP(W4)
  • HLA-DP1A
  • HLA-SB alpha chain
  • HLASB
  • MHC class II DP3-alpha
  • MHC class II DPA1
Gene NameHLA-DPA1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008837|HLA class II histocompatibility antigen, DP alpha 1 chain
MRPEDRMFHIRAVILRALSLAFLLSLRGAGAIKADHVSTYAAFVQTHRPTGEFMFEFDED
EMFYVDLDKKETVWHLEEFGQAFSFEAQGGLANIAILNNNLNTLIQRSNHTQATNDPPEV
TVFPKEPVELGQPNTLICHIDKFFPPVLNVTWLCNGELVTEGVAESLFLPRTDYSFHKFH
YLTFVPSAEDFYDCRVEHWGLDQPLLKHWEAQEPIQMPETTETVLCALGLVLGLVGIIVG
TVLIIKSLRSGHDPRAQGTL
Number of residues260
Molecular Weight29380.345
Theoretical pINot Available
GO Classification
Functions
  • peptide antigen binding
  • MHC class II receptor activity
Processes
  • T cell costimulation
  • T cell receptor signaling pathway
  • interferon-gamma-mediated signaling pathway
  • immune response
  • cellular response to interferon-gamma
  • positive regulation of T cell activation
  • antigen processing and presentation of exogenous peptide antigen via MHC class II
  • cytokine-mediated signaling pathway
  • positive regulation of T cell proliferation
  • positive regulation of interferon-gamma production
Components
  • endosome membrane
  • transport vesicle membrane
  • ER to Golgi transport vesicle membrane
  • plasma membrane
  • cell surface
  • integral component of plasma membrane
  • clathrin-coated endocytic vesicle membrane
  • Golgi membrane
  • integral component of lumenal side of endoplasmic reticulum membrane
  • MHC class II protein complex
  • endocytic vesicle membrane
  • trans-Golgi network membrane
  • lysosomal membrane
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.
Pfam Domain Function
Transmembrane Regions223-245
GenBank Protein IDNot Available
UniProtKB IDP20036
UniProtKB Entry NameDPA1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0013445|HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)
ATGCGCCCTGAAGACAGAATGTTCCATATCAGAGCTGTGATCTTGAGAGCCCTCTCCTTG
GCTTTCCTGCTGAGTCTCCGAGGAGCTGGGGCCATCAAGGCGGACCATGTGTCAACTTAT
GCCGCGTTTGTACAGACGCATAGACCAACAGGGGAGTTTATGTTTGAATTTGATGAAGAT
GAGATGTTCTATGTGGATCTGGACAAGAAGGAGACCGTCTGGCATCTGGAGGAGTTTGGC
CAAGCCTTTTCCTTTGAGGCTCAGGGCGGGCTGGCTAACATTGCTATATTGAACAACAAC
TTGAATACCTTGATCCAGCGTTCCAACCACACTCAGGCCACCAACGATCCCCCTGAGGTG
ACCGTGTTTCCCAAGGAGCCTGTGGAGCTGGGCCAGCCCAACACCCTCATCTGCCACATT
GACAAGTTCTTCCCACCAGTGCTCAACGTCACGTGGCTGTGCAACGGGGAGCTGGTCACT
GAGGGTGTCGCTGAGAGCCTCTTCCTGCCCAGAACAGATTACAGCTTCCACAAGTTCCAT
TACCTGACCTTTGTGCCCTCAGCAGAGGACTTCTATGACTGCAGGGTGGAGCACTGGGGC
TTGGACCAGCCGCTCCTCAAGCACTGGGAGGCCCAAGAGCCAATCCAGATGCCTGAGACA
ACGGAGACTGTGCTCTGTGCCCTGGGCCTGGTGCTGGGCCTAGTCGGCATCATCGTGGGC
ACCGTCCTCATCATAAAGTCTCTGCGTTCTGGCCATGACCCCCGGGCCCAGGGGACCCTG
TGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:4938
Chromosome Location6
LocusNot Available
References
  1. Lawrance SK, Das HK, Pan J, Weissman SM: The genomic organisation and nucleotide sequence of the HLA-SB(DP) alpha gene. Nucleic Acids Res. 1985 Oct 25;13(20):7515-28. 2997750
  2. Gustafsson K, Widmark E, Jonsson AK, Servenius B, Sachs DH, Larhammar D, Rask L, Peterson PA: Class II genes of the human major histocompatibility complex. Evolution of the DP region as deduced from nucleotide sequences of the four genes. J Biol Chem. 1987 Jun 25;262(18):8778-86. 3036829
  3. Young JA, Lindsay J, Bodmer JG, Trowsdale J: Epitope recognition by a DP alpha chain-specific monoclonal antibody (DP11.1) is influenced by the interaction between the DP alpha chain and its polymorphic DP beta chain partner. Hum Immunol. 1988 Sep;23(1):37-44. 2461352
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. 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
  6. 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. 6584734
  7. Muntau B, Thye T, Pirmez C, Horstmann RD: A novel DPA1 allele (DPA1*0203) composed of known epitopes. Tissue Antigens. 1997 Jun;49(6):668-9. 9234495
  8. Steiner LL, Cavalli A, Zimmerman PA, Boatin BA, Titanji VP, Bradley JE, Lucius R, Nutman TB, Begovich AB: Three new DP alleles identified in sub-Saharan Africa: DPB1*7401, DPA1*02013, and DPA1*0302. Tissue Antigens. 1998 Jun;51(6):653-7. 9694359
  9. Rozemuller EH, Bouwens AG, van Oort E, Versluis LF, Marsh SG, Bodmer JG, Tilanus MG: Sequencing-based typing reveals new insight in HLA-DPA1 polymorphism. Tissue Antigens. 1995 Jan;45(1):57-62. 7725312
  10. McDaniel DO, Nguyen C, McDaniel LS: A new HLA-DPA1 allele, DPA1*02016, identified in African-American population. Tissue Antigens. 2000 Aug;56(2):197-8. 11019928
  11. Luo M, Bamforth J, Gill K, Cohen C, Brunham RC, Plummer FA: High-resolution sequence-based DPA1 typing identified two novel DPA1 alleles, DPA1*010303 and DPA1*0303, from a Kenyan population. Tissue Antigens. 2005 Jan;65(1):120-2. 15663751
  12. Peterson TA, Luo M, Mao X, Brunham RC, Plummer FA: Identification of a novel DPA1 allele, DPA1*010602, in an East African population. Hum Immunol. 2008 Dec;69(12):885-6. doi: 10.1016/j.humimm.2008.09.001. Epub 2008 Oct 7. 18838095
  13. Lee KW: Description of two novel HLA-DPA1 alleles: DPA1*0110 and DPA1*010304. Tissue Antigens. 2008 Jun;71(6):575-7. doi: 10.1111/j.1399-0039.2008.01035.x. Epub 2008 Mar 29. 18380777
  14. Zhao H, Dai WJ, He YM, Zhu FM, Yan LX: A novel HLA-DPA1*0204 allele was identified in a Chinese individual. Tissue Antigens. 2008 Jun;71(6):577-8. doi: 10.1111/j.1399-0039.2008.01046.x. 18489436
  15. May J, Kretschmer C, Schnittger L, Striecker R, Kremsner PG, Meyer CG: DPA1*0105, a novel DPA1 variant in a negroid population. Tissue Antigens. 1996 Nov;48(5):593-4. 8988544
  16. Rozemuller EH, Versluis LF, Bouwens AG, Tilanus MG: Exon 2, 3, and 4 polymorphism of HLA-DPA1. Immunogenetics. 1995;41(1):53. 7806277
  17. Trowsdale J, Lee J, Carey J, Grosveld F, Bodmer J, Bodmer W: Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1972-6. 6300884
  18. Cresswell P: Invariant chain structure and MHC class II function. Cell. 1996 Feb 23;84(4):505-7. 8598037
  19. 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
  20. 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
  21. Menendez-Benito V, Neefjes J: Autophagy in MHC class II presentation: sampling from within. Immunity. 2007 Jan;26(1):1-3. 17241953
  22. 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
  23. 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
  24. 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
  25. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569