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HLA-DRA major histocompatibility complex, class II, DR alpha [ Homo sapiens (human) ]

Gene ID: 3122, updated on 27-Jun-2020

Summary

Official Symbol
HLA-DRAprovided by HGNC
Official Full Name
major histocompatibility complex, class II, DR alphaprovided by HGNC
Primary source
HGNC:HGNC:4947
See related
Ensembl:ENSG00000204287 MIM:142860
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HLA-DRA1
Summary
HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, 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). 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. [provided by RefSeq, Jul 2008]
Expression
Broad expression in lymph node (RPKM 921.6), lung (RPKM 809.6) and 24 other tissues See more
Orthologs

Genomic context

See HLA-DRA in Genome Data Viewer
Location:
6p21.32
Exon count:
5
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (32439887..32445046)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32407619..32412823)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene TSBP1 and BTNL2 antisense RNA 1 Neighboring gene testis expressed basic protein 1 Neighboring gene RNA, U6 small nuclear 603, pseudogene Neighboring gene HLA complex group 23 Neighboring gene butyrophilin like 2 Neighboring gene major histocompatibility complex, class II, DR beta 9 (pseudogene) Neighboring gene major histocompatibility complex, class II, DR beta 5

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations.
NHGRI GWA Catalog
A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).
NHGRI GWA Catalog
A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia.
NHGRI GWA Catalog
An association between anti-nuclear antibody and HLA class II locus and heterogeneous characteristics of staining patterns: The Nagahama Study.
NHGRI GWA Catalog
Biological, clinical and population relevance of 95 loci for blood lipids.
NHGRI GWA Catalog
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
NHGRI GWA Catalog
Discovery and refinement of loci associated with lipid levels.
NHGRI GWA Catalog
Frontotemporal dementia and its subtypes: a genome-wide association study.
NHGRI GWA Catalog
Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3.
NHGRI GWA Catalog
Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
NHGRI GWA Catalog
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
NHGRI GWA Catalog
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
NHGRI GWA Catalog
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
NHGRI GWA Catalog
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
NHGRI GWA Catalog
Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).
NHGRI GWA Catalog
Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.
NHGRI GWA Catalog
Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.
NHGRI GWA Catalog
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.
NHGRI GWA Catalog
Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis.
NHGRI GWA Catalog
Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Identification of a novel Parkinson's disease locus via stratified genome-wide association study.
NHGRI GWA Catalog
Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
NHGRI GWA Catalog
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
NHGRI GWA Catalog
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
NHGRI GWA Catalog
Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.
NHGRI GWA Catalog
Risk alleles for multiple sclerosis identified by a genomewide study.
NHGRI GWA Catalog
Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility.
NHGRI GWA Catalog
Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.
NHGRI GWA Catalog
Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
NHGRI GWA Catalog
Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Clinical trophoblast microparticle samples from HIV-1 infected patients upregulates HLA-DR (MHC-II) expression on dendritic cells upon exposure PubMed
HIV-1 infection upregulates HLA-DR (MHC-II) and CD38 on CD4+ and CD8+ T cells in clinical, patient samples PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env CD4-mediated endocytosis of HIV-1 gp120 results in MHC-II (HLA-DR) presentation to CD4+ T cells PubMed
env Inhibition of CpG-B-induced maturation of plasmacytoid dendritic cells by HIV-1 gp120 results in downregulation of CD40, CD83, CCR7, and HLA-DR expression PubMed
env CD4+ T cells infected with CCR5-tropic HIV-1 have significantly higher levels of activation-marker expression (e.g. CD25, CD71 and HLA-DR) than CD4+ T lymphocytes infected with CXCR4-tropic HIV-1 PubMed
env HIV envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Ag PubMed
env Genetic variability in HIV-1 gp120 affects its interactions with HLA-DR molecules and T cell receptor PubMed
env Amino acid residues 42-49 in the V1 region of CD4 are involved in the interaction between HIV-1 gp120 and class II major histocompatibility complex molecules PubMed
Envelope surface glycoprotein gp160, precursor env Processing of HIV-1 gp160 to gp120 and gp41 is necessary for the association of HIV-1 envelope glycoproteins with class II MHC PubMed
env Antibodies against cell surface molecules LFA-1, ICAM-1, HLA-DR, and CD28 inhibit the HIV-1 gp160-induced B cell differentiation response; gp160 also induces IL-6R and CD23 molecule expression on B cells PubMed
Envelope transmembrane glycoprotein gp41 env Soluble HIV-1 gp41 enhancement effects on MHC class I and II antigen expression can be inhibited by soluble gp41-binding proteins of 45, 49 and 62 kD from human B cells PubMed
env Soluble HIV-1 gp41 can selectively enhance MHC class I and II expression on human B cells, but does not increase expression of other cell surface antigens such as CD21 and CD54 (ICAM-1) PubMed
env A 43-amino-acid sequence between amino acids 708 and 750 in the HIV-1 gp41(TM) cytoplasmic tail is required for efficient incorporation of HLA class II proteins into virions PubMed
Nef nef HIV-1 Nef cloned from subjects with early/acute progressive HIV infection downregulates HLA-DR in 721.221 cells to a greater extent relative to HIV-1 Nef cloned from subjects with chronic progressive infection PubMed
nef Expression of patient-derived HIV-1 nef alleles downregulates MHC-II cell surface expression in activated CD4+ T cells PubMed
nef HIV-1 Nef impairs IL-4/GM-CSF-stimulated THP-1 differentiation towards immature DCs, which leads to the lower levels of CD11C, CD40, and HLA-DR protein expression from the cell surface PubMed
nef Nef-triggered MHCII endocytosis requires Rab5 activity and lyst function, whereas lysosomal trafficking of internalized MHCII molecules requires Rab7 activity PubMed
nef Four large regions (residues 1-36, 66-97, 117-147, and 182-205) of HIV-1 Nef bind efficiently to eight HLA-DR molecules PubMed
nef HIV-1 Nef-pulsed mDCs downregulate HLA-DR expression and upregulate CD25 and CCR7 expression in NK cells PubMed
nef HIV-1 Nef expression inhibits MHC II presentation of viral antigens in infected antigen-presenting cells PubMed
nef HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules PubMed
Pr55(Gag) gag In human macrophages, HIV-1 Gag proteins co-localize with MHC II (HLA-DR), CD63, and Lamp1 in MHC II compartments PubMed
gag Expression of CD80, CD83, CD86, and HLA-DR molecules are significantly downregulated in mature dendritic cells after transduction with ubiquitinated Gag compared to unubiquitinated Gag constructs PubMed
gag Two peptides of the CA domain of HIV-1 Gag, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, are presented on MHC II molecules of dendritic cells and have similar sensitivity for antigen-specific T cells PubMed
gag Expression of MARCH-8 inhibits HLA-DR-mediated enhancement of mature Gag products internalization by downregulating cell surface HLA-DR PubMed
gag The Gag late-budding domain PTAP motif and the cytosolic tails of the HLA-DR alpha and beta chains are required for HLA-DR-mediated Gag accumulation in late endosomal/multivesicular bodies (LE/MVB) PubMed
gag Dynamin-dependent endocytosis is required for intracellular accumulation of HIV-1 Gag in presence of HLA-DR PubMed
gag HIV-1 Gag virus-like particle-induced monocyte activation is shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54) PubMed
gag HIV-1 Gag virus-like particles efficiently activate human monocyte-derived dendritic cells (MDDC) and induce MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II PubMed
gag Human Leukocyte Antigen DR (HLA-DR), Major Histocompatibility Complex class II molecules (MHC-II) induce a relocation of Gag to late endosomal/multivesicular bodies (LE/MVB) and increase the accumulation of viral particles assembling intracellularly PubMed
gag HIV-1 Gag expression is able to induce HLA-DR cell-surface localization in H78-C10.0 cells PubMed
Tat tat Treatment of PBMCs with HIV-1 Tat significantly enhances the generation of monocytic myeloid-derived suppressor cells expressing no or very low levels of HLA-DR PubMed
tat HIV-1 Tat upregulates HLA-DR expression in monocyte-derived dendritic cells and T cells, thereby driving T cell-mediated immune responses and activation PubMed
tat HIV-1 Tat downregulates expression of MHC class II genes in antigen-presenting cells (APC) by inhibiting the transactivator of MHC class II genes, CIITA PubMed
Vpu vpu HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells PubMed
capsid gag HIV-1 CA co-localizes with HLA-DR in human monocyte-derived dendritic cells PubMed
gag HIV-1 Capsid (p24) inhibits interferon gamma induced increases in HLA-DR and cytochrome B heavy chain mRNA levels in the human monocyte-like cell line THP1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ51114

Gene Ontology Provided by GOA

Function Evidence Code Pubs
MHC class II protein complex binding HDA PubMed 
MHC class II receptor activity NAS
Non-traceable Author Statement
more info
PubMed 
peptide antigen binding IDA
Inferred from Direct Assay
more info
PubMed 
polysaccharide binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Component Evidence Code Pubs
ER to Golgi transport vesicle membrane TAS
Traceable Author Statement
more info
 
Golgi membrane TAS
Traceable Author Statement
more info
 
MHC class II protein complex IDA
Inferred from Direct Assay
more info
PubMed 
MHC class II protein complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
clathrin-coated endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
integral component of lumenal side of endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
integral component of plasma membrane NAS
Non-traceable Author Statement
more info
PubMed 
late endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
lysosomal membrane IDA
Inferred from Direct Assay
more info
PubMed 
lysosomal membrane TAS
Traceable Author Statement
more info
 
lysosome IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
trans-Golgi network membrane TAS
Traceable Author Statement
more info
 
transport vesicle membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
HLA class II histocompatibility antigen, DR alpha chain
Names
MHC class II antigen DRA
histocompatibility antigen HLA-DR alpha

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_019111.5NP_061984.2  HLA class II histocompatibility antigen, DR alpha chain precursor

    See identical proteins and their annotated locations for NP_061984.2

    Status: REVIEWED

    Source sequence(s)
    BC032350, BC071659, BG548634, BM849755
    Consensus CDS
    CCDS4750.1
    UniProtKB/Swiss-Prot
    P01903
    UniProtKB/TrEMBL
    A0A0G2JMH6
    Related
    ENSP00000378786.2, ENST00000395388.7
    Conserved Domains (3) summary
    cd05767
    Location:111204
    IgC_MHC_II_alpha; Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00993
    Location:29106
    MHC_II_alpha; Class II histocompatibility antigen, alpha domain
    pfam16196
    Location:201253
    C1-set_C; C1-set C-terminal domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    32439887..32445046
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p13 ALT_REF_LOCI_2

    Range
    3878013..3883135
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p13 ALT_REF_LOCI_3

    Range
    3680192..3685357
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p13 ALT_REF_LOCI_4

    Range
    3744104..3749270
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p13 ALT_REF_LOCI_5

    Range
    3780853..3786018
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p13 ALT_REF_LOCI_6

    Range
    3662936..3668101
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p13 ALT_REF_LOCI_7

    Range
    3755030..3760195
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_8

Genomic

  1. NT_187692.1 Reference GRCh38.p13 ALT_REF_LOCI_8

    Range
    9687..14846 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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