HLA-DRA

Major histocompatibility complex, class II, DR alpha

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes

1A6A, 1AQD, 1BX2, 1D5M, 1D5X, 1D5Z, 1D6E, 1DLH, 1FV1, 1FYT, 1H15, 1HQR, 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, 2SEB, 2WBJ, 2XN9, 3C5J, 3L6F, 3O6F, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 3S4S, 3S5L, 3T0E, 4AEN, 4AH2, 4C56, 4E41, 4FQX, 4GBX, 4H1L, 4H25, 4H26, 4I5B, 4IS6, 4MCY, 4MCZ, 4MD0, 4MD4, 4MD5, 4MDI, 4MDJ, 4OV5

Identifiers

Symbols

HLA-DRA ; HLA-DRA1; MLRW

External IDs

OMIM: 142860 MGI: 95900 HomoloGene: 7751 GeneCards: HLA-DRA Gene

Gene ontology
Molecular function	• MHC class II protein complex binding • MHC class II receptor activity • peptide antigen binding
Cellular component	• Golgi membrane • lysosome • lysosomal membrane • plasma membrane • integral component of plasma membrane • cell surface • ER to Golgi transport vesicle membrane • transport vesicle membrane • endocytic vesicle membrane • clathrin-coated endocytic vesicle membrane • late endosome membrane • trans-Golgi network membrane • MHC class II protein complex • extracellular exosome • integral component of lumenal side of endoplasmic reticulum membrane
Biological process	• peptide antigen assembly with MHC class II protein complex • antigen processing and presentation of peptide or polysaccharide antigen via MHC class II • polysaccharide assembly with MHC class II protein complex • immune response • viral process • cytokine-mediated signaling pathway • antigen processing and presentation of exogenous peptide antigen via MHC class II • T cell costimulation • T cell receptor signaling pathway • cognition • interferon-gamma-mediated signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 6:
32.44 – 32.45 Mb

Chr 17:
33.95 – 33.95 Mb

PubMed search

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene.^[1] 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).

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).^[1]

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.^[1]

Alleles

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

DRA01:01 DRA01:02:01 DRA*01:02:02

References

1 2 3 "Entrez Gene: HLA-DRA major histocompatibility complex, class II, DR alpha".

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. 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.

PDB gallery

1a6a: THE STRUCTURE OF AN INTERMEDIATE IN CLASS II MHC MATURATION: CLIP BOUND TO HLA-DR3

1aqd: HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE

1bx2: CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101,DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN

1d5m: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB

1d5x: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH DIPEPTIDE MIMETIC AND SEB

1d5z: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDOMIMETIC AND SEB

1d6e: CRYSTAL STRUCTURE OF HLA-DR4 COMPLEX WITH PEPTIDOMIMETIC AND SEB

1dlh: CRYSTAL STRUCTURE OF THE HUMAN CLASS II MHC PROTEIN HLA-DR1 COMPLEXED WITH AN INFLUENZA VIRUS PEPTIDE

1fv1: STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES

1fyt: CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1

1h15: X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE

1hqr: CRYSTAL STRUCTURE OF A SUPERANTIGEN BOUND TO THE HIGH-AFFINITY, ZINC-DEPENDENT SITE ON MHC CLASS II

1hxy: CRYSTAL STRUCTURE OF STAPHYLOCOCCAL ENTEROTOXIN H IN COMPLEX WITH HUMAN MHC CLASS II

1j8h: Crystal Structure of a Complex of a Human alpha/beta-T cell Receptor, Influenza HA Antigen Peptide, and MHC Class II Molecule, HLA-DR4

1jwm: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1(HA peptide 306-318) with the Superantigen SEC3

1jws: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the Superantigen SEC3 Variant 3B1

1jwu: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the superantigen SEC3 Variant 3B2

1kg0: Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC class II Receptor HLA-DR1

1klg: Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1klu: Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1lo5: Crystal structure of the D227A variant of Staphylococcal enterotoxin A in complex with human MHC class II

1pyw: Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1r5i: Crystal structure of the MAM-MHC complex

1seb: COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB

1sje: HLA-DR1 complexed with a 16 residue HIV capsid peptide bound in a hairpin conformation

1sjh: HLA-DR1 complexed with a 13 residue HIV capsid peptide

1t5w: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR)

1t5x: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2

1ymm: TCR/HLA-DR2b/MBP-peptide complex

1zgl: Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a

2g9h: Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule

2iam: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

2ian: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

2icw: Crystal structure of a complete ternary complex between TCR, superantigen, and peptide-MHC class II molecule

Image:PDB_2oje_EBI.jpg

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Image:PDB_2seb_EBI.jpg

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Surface antigens

Major histocompatibility complex/
Human leukocyte antigen

MHC class I	HLA-A HLA-B HLA-C HLA-E HLA-F HLA-G

MHC class II	HLA-DM α β HLA-DO α β HLA-DP α1 β1 HLA-DQ α1 α2 β1 β2 β3 HLA-DR α β1 β3 β4 β5 Minor histocompatibility antigen

Other

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HLA-DRA

Function

Gene structure and polymorphisms

Alleles

See also

References

Further reading