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

    Gene ID: 3122, updated on 2-Mar-2021

    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. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. 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, Aug 2020]
    Expression
    Broad expression in lymph node (RPKM 921.6), lung (RPKM 809.6) and 24 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See HLA-DRA in Genome Data Viewer
    Location:
    6p21.32
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    109.20210226 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (32439887..32445046)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32407664..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

    Associated conditions

    Description Tests
    A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations.
    GeneReviews: Not available
    A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).
    GeneReviews: Not available
    A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia.
    GeneReviews: Not available
    An association between anti-nuclear antibody and HLA class II locus and heterogeneous characteristics of staining patterns: The Nagahama Study.
    GeneReviews: Not available
    Biological, clinical and population relevance of 95 loci for blood lipids.
    GeneReviews: Not available
    Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
    GeneReviews: Not available
    Discovery and refinement of loci associated with lipid levels.
    GeneReviews: Not available
    Frontotemporal dementia and its subtypes: a genome-wide association study.
    GeneReviews: Not available
    Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3.
    GeneReviews: Not available
    Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
    GeneReviews: Not available
    Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
    GeneReviews: Not available
    Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
    GeneReviews: Not available
    Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
    GeneReviews: Not available
    Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
    GeneReviews: Not available
    Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).
    GeneReviews: Not available
    Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.
    GeneReviews: Not available
    Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.
    GeneReviews: Not available
    Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.
    GeneReviews: Not available
    Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis.
    GeneReviews: Not available
    Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.
    GeneReviews: Not available
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    GeneReviews: Not available
    Identification of a novel Parkinson's disease locus via stratified genome-wide association study.
    GeneReviews: Not available
    Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
    GeneReviews: Not available
    Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
    GeneReviews: Not available
    Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
    GeneReviews: Not available
    Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.
    GeneReviews: Not available
    Risk alleles for multiple sclerosis identified by a genomewide study.
    GeneReviews: Not available
    Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility.
    GeneReviews: Not available
    Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.
    GeneReviews: Not available
    Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
    GeneReviews: Not available
    Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
    GeneReviews: Not available

    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 
    T cell receptor binding IDA
    Inferred from Direct Assay
    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 
    Process Evidence Code Pubs
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    antigen processing and presentation of endogenous peptide antigen via MHC class II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antigen processing and presentation of exogenous peptide antigen via MHC class II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antigen processing and presentation of exogenous peptide antigen via MHC class II TAS
    Traceable Author Statement
    more info
     
    antigen processing and presentation of peptide or polysaccharide antigen via MHC class II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cognition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    immune response NAS
    Non-traceable Author Statement
    more info
    PubMed 
    interferon-gamma-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    myeloid dendritic cell antigen processing and presentation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peptide antigen assembly with MHC class II protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of CD4-positive, alpha-beta T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of T cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of memory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of T-helper cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    viral process IEA
    Inferred from Electronic Annotation
    more info
     
    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 
    immunological synapse IDA
    Inferred from Direct Assay
    more info
    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)

    NEW Try the new Transcript table

    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 109.20210226

    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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