HLA-DRA

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 Contents Function ; Gene structure and polymorphisms ; Alleles ; See also ; References ; Further reading ;
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)
End	32,445,046 bp
RNA expression pattern
	Top expressed in
	monocyte; ; appendix; ; lymph node; ; gallbladder; ; duodenum; ; spleen; ; upper lobe of left lung; ; right lung; ; smooth muscle tissue; ; rectum;
	n/a
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	peptide antigen binding ; MHC class II receptor activity ; MHC class II protein complex binding ; 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 ; plasma 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 ; viral process ; T cell receptor signaling pathway ; adaptive immune response ;
	Sources:Amigo / QuickGO
Orthologs
	3122
	100504404
ENSG00000206308 ; ENSG00000228987 ; ENSG00000230726 ; ENSG00000204287 ; ENSG00000227993 ;
	ENSG00000226260 ; ENSG00000234794 ; ENSG00000277263
	ENSMUSG00000036322
	P01903
	P04224 ; P01904
	NM_019111
	NM_010381
	NP_061984
	NP_034511
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 22, 2023

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene.^[4] 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).^[4]

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.^[4]

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

Related Research Articles

<span class="mw-page-title-main">HLA-DR</span> Subclass of HLA-D antigens that consist of alpha and beta chains

HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). HLA were originally defined as cell surface antigens that mediate graft-versus-host disease. Identification of these antigens has led to greater success and longevity in organ transplant.

<span class="mw-page-title-main">HLA-DRB1</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. DRB1 encodes the most prevalent beta subunit of HLA-DR. DRB1 alleles, especially those encoding amino acid sequence changes at positions 11 and 13, are associated risk of rheumatoid arthritis.

MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.

<span class="mw-page-title-main">HLA-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

<span class="mw-page-title-main">HLA-DR53</span>

HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins.

Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.

<span class="mw-page-title-main">HLA-DRB5</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.

<span class="mw-page-title-main">HLA-DR51</span>

HLA-DR51 is a HLA-DR serotype that recognizes the antigens encoded by the minor DR locus HLA-DRB5.

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).

<span class="mw-page-title-main">Major histocompatibility complex, class II, DQ alpha 1</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.

<span class="mw-page-title-main">HLA-DRB3</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DRB3-1 beta chain is a protein that in humans is encoded by the HLA-DRB3 gene.

HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include IFN-gamma signaling and CDK-mediated phosphorylation and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication.

HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.

HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.

HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.

HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system.

HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.

CD8a, is a human gene.

References

1 2 3 ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794, ENSG00000277263 GRCh38: Ensembl release 89: ENSG00000206308, ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794, ENSG00000277263 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 3 "Entrez Gene: HLA-DRA major histocompatibility complex, class II, DR alpha".

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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. S2CID 34731265.
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. S2CID 10116507.
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. doi:10.4049/jimmunol.144.2.526. PMID 1967269.
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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. doi:10.4049/jimmunol.145.8.2730. 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. Bibcode:1989Natur.339..548C. doi: 10.1038/339548a0 . PMID 2543930. S2CID 4246781.
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[refGRCh38Ensembl-1] 1 2 3 ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794, ENSG00000277263 GRCh38: Ensembl release 89: ENSG00000206308, ENSG00000228987, ENSG00000230726, ENSG00000204287, ENSG00000227993, ENSG00000226260, ENSG00000234794, ENSG00000277263 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Entrez_Gene_3122-4] 1 2 3 "Entrez Gene: HLA-DRA major histocompatibility complex, class II, DR alpha".

[1]

[2]

[3]

[4]

v t e Major histocompatibility complex classes
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
Other	Human leukocyte antigen Minor histocompatibility antigen Blood transfusion Arrestin Calgranulin Human blood group systems Cell adhesion molecules Cluster of differentiation

HLA-DRA

Contents

Function

Gene structure and polymorphisms

Alleles

See also

Related Research Articles

References

Further reading