HLA-DRA

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene.[5] HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms (2 alleles of DRB1 and two alleles from DRB3, DRB4 or DRB5).

HLA-DRA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A6A, 1AQD, 1BX2, 1D5M, 1D5X, 1D5Z, 1D6E, 1DLH, 1FV1, 1FYT, 1H15, 1HXY, 1J8H, 1JWM, 1JWS, 1JWU, 1KG0, 1KLG, 1KLU, 1LO5, 1PYW, 1R5I, 1SEB, 1SJE, 1SJH, 1T5W, 1T5X, 1YMM, 1ZGL, 2FSE, 2G9H, 2IAM, 2IAN, 2ICW, 2IPK, 2OJE, 2Q6W, 2WBJ, 2XN9, 3C5J, 3L6F, 3O6F, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 3S4S, 3S5L, 3T0E, 4AEN, 4AH2, 4E41, 4FQX, 4GBX, 4H1L, 4C56, 4H25, 4H26, 4I5B, 4IS6, 4MCY, 4MCZ, 4MD0, 4MD4, 4MD5, 4MDI, 4MDJ, 4OV5, 4Y19, 4Y1A, 4X5X, 4X5W
Identifiers
Aliases	HLA-DRA, HLA-DRA1, MLRW, major histocompatibility complex, class II, DR alpha
External IDs	OMIM: 142860 MGI: 95900 HomoloGene: 7751 GeneCards: HLA-DRA
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.32 Start 32,439,878 bp[1] End 32,445,046 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B1|17 17.98 cM Start 34,341,959 bp[2] End 34,344,645 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptide antigen binding • MHC class II receptor activity • MHC class II protein complex binding • GO:0001948 protein binding Cellular component • integral component of membrane • endocytic vesicle membrane • clathrin-coated endocytic vesicle membrane • endosome • Golgi apparatus • trans-Golgi network membrane • endoplasmic reticulum membrane • membrane • late endosome membrane • Golgi membrane • cell membrane • transport vesicle membrane • integral component of plasma membrane • cell surface • lysosomal membrane • endoplasmic reticulum • ER to Golgi transport vesicle membrane • lysosome • integral component of lumenal side of endoplasmic reticulum membrane • endosome membrane • extracellular exosome • MHC class II protein complex Biological process • antigen processing and presentation • antigen processing and presentation of exogenous peptide antigen via MHC class II • cognition • interferon-gamma-mediated signaling pathway • immune system process • T cell costimulation • antigen processing and presentation of peptide or polysaccharide antigen via MHC class II • immune response • peptide antigen assembly with MHC class II protein complex • GO:0022415 viral process • T cell receptor signaling pathway • adaptive immune response Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3122	100504404
Ensembl	ENSG00000206308 ENSG00000228987 ENSG00000230726 ENSG00000204287 ENSG00000227993 ENSG00000226260 ENSG00000234794	ENSMUSG00000036322
UniProt	P01903	P04224 P01904
RefSeq (mRNA)	NM_019111	NM_010381
RefSeq (protein)	NP_061984	NP_034511
Location (UCSC)	Chr 6: 32.44 – 32.45 Mb	Chr 17: 34.34 – 34.34 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The polypeptide subunit encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages).[5]

Gene structure and polymorphisms

The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5.[5]

Alleles

There are two different HLA-DRA chains in the human population coded by three different DRA alleles:

DRA*01:01 DRA*01:02:01 DRA*01:02:02

See also

• HLA-DR

References

1. ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794 GRCh38: Ensembl release 89: ENSG00000206308, ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036322 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: HLA-DRA major histocompatibility complex, class II, DR alpha".

Further reading

• Bénichou S, Benmerah A (2003). "[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]". Med Sci (Paris). 19 (1): 100–6. doi:10.1051/medsci/2003191100. PMID 12836198.
• Tolstrup M, Ostergaard L, Laursen AL, et al. (2004). "HIV/SIV escape from immune surveillance: focus on Nef". Curr. HIV Res. 2 (2): 141–51. doi:10.2174/1570162043484924. PMID 15078178.
• Anderson JL, Hope TJ (2005). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS Reports. 1 (1): 47–53. doi:10.1007/s11904-004-0007-x. PMID 16091223.
• Li L, Li HS, Pauza CD, et al. (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. doi:10.1038/sj.cr.7290370. PMID 16354571.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Matsushima GK, Itoh-Lindstrom Y, Ting JP (1992). "Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements". Mol. Cell. Biol. 12 (12): 5610–9. doi:10.1128/MCB.12.12.5610. PMC 360500. PMID 1448091.
• Schaiff WT, Hruska KA, McCourt DW, et al. (1992). "HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells". J. Exp. Med. 176 (3): 657–66. doi:10.1084/jem.176.3.657. PMC 2119345. PMID 1512535.
• Piatier-Tonneau D, Gastinel LN, Amblard F, et al. (1991). "Interaction of CD4 with HLA class II antigens and HIV gp120". Immunogenetics. 34 (2): 121–8. doi:10.1007/BF00211424. PMID 1869305.
• Nong Y, Kandil O, Tobin EH, et al. (1991). "The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1". Cell. Immunol. 132 (1): 10–6. doi:10.1016/0008-8749(91)90002-S. PMID 1905983.
• Rosenstein Y, Burakoff SJ, Herrmann SH (1990). "HIV-gp120 can block CD4-class II MHC-mediated adhesion". J. Immunol. 144 (2): 526–31. PMID 1967269.
• Callahan KM, Fort MM, Obah EA, et al. (1990). "Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor". J. Immunol. 144 (9): 3341–6. PMID 1970352.
• Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ (1991). "Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules". Proc. Natl. Acad. Sci. U.S.A. 87 (22): 9052–6. doi:10.1073/pnas.87.22.9052. PMC 55099. PMID 1978941.
• Koppelman B, Cresswell P (1990). "Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain". J. Immunol. 145 (8): 2730–6. PMID 2212658.
• Clayton LK, Sieh M, Pious DA, Reinherz EL (1989). "Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding". Nature. 339 (6225): 548–51. doi:10.1038/339548a0. PMID 2543930.
• Diamond DC, Sleckman BP, Gregory T, et al. (1988). "Inhibition of CD4+ T cell function by the HIV envelope protein, gp120". J. Immunol. 141 (11): 3715–7. PMID 2846691.
• Tjernlund U, Scheynius A, Johansson C, et al. (1989). "T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens". Scand. J. Immunol. 28 (6): 667–73. doi:10.1111/j.1365-3083.1988.tb01500.x. PMID 3266023.
• Andrieu JM, Even P, Venet A (1986). "AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications". AIDS Research. 2 (3): 163–74. doi:10.1089/aid.1.1986.2.163. PMID 3489470.
• Das HK, Lawrance SK, Weissman SM (1983). "Structure and nucleotide sequence of the heavy chain gene of HLA-DR". Proc. Natl. Acad. Sci. U.S.A. 80 (12): 3543–7. doi:10.1073/pnas.80.12.3543. PMC 394085. PMID 6304715.
• Schamboeck A, Korman AJ, Kamb A, Strominger JL (1984). "Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain". Nucleic Acids Res. 11 (24): 8663–75. doi:10.1093/nar/11.24.8663. PMC 326615. PMID 6324094.
• Das HK, Biro PA, Cohen SN, et al. (1983). "Use of synthetic oligonucleotide probes complementary to genes for human HLA-DR alpha and beta as extension primers for the isolation of 5'-specific genomic clones". Proc. Natl. Acad. Sci. U.S.A. 80 (6): 1531–5. doi:10.1073/pnas.80.6.1531. PMC 393635. PMID 6403940.