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    HLA-DRB4 major histocompatibility complex, class II, DR beta 4 [ Homo sapiens (human) ]

    Gene ID: 3126, updated on 3-Apr-2024

    Summary

    Official Symbol
    HLA-DRB4provided by HGNC
    Official Full Name
    major histocompatibility complex, class II, DR beta 4provided by HGNC
    Primary source
    HGNC:HGNC:4952
    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
    DR4; DRB4; HLA-DRB; HLA-DR4B; HLA-DRB4*
    Summary
    HLA-DRB4 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) 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. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene. [provided by RefSeq, Feb 2020]
    Annotation information
    Annotation category: only annotated on alternate loci in reference assembly
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    Genomic context

    See HLA-DRB4 in Genome Data Viewer
    Location:
    6p21.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_4) NT_167246.2 (3840427..3855395, complement)
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_5) NT_167247.2 (3876736..3891707, complement)
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_7) NT_167249.2 (3851133..3866104, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_4) NT_167246.1 (3846047..3861015, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_5) NT_167247.1 (3882321..3897292, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_7) NT_167249.1 (3850431..3865402, complement)

    NT_167246.2Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene MPRA-validated peak5756 silencer Neighboring gene major histocompatibility complex, class II, DR beta 9 (pseudogene) Neighboring gene HLA class II histocompatibility antigen, DR beta 4 chain-like Neighboring gene protein FAM136A-like Neighboring gene protein activator of interferon induced protein kinase EIF2AK2 pseudogene 1

    NT_167247.2Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene MPRA-validated peak5756 silencer Neighboring gene major histocompatibility complex, class II, DR beta 9 (pseudogene) Neighboring gene major histocompatibility complex, class II, DQ alpha 1 Neighboring gene HLA-DQB1 antisense RNA 1 Neighboring gene major histocompatibility complex, class II, DQ beta 1

    NT_167249.2Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene MPRA-validated peak5756 silencer Neighboring gene major histocompatibility complex, class II, DR beta 9 (pseudogene) Neighboring gene major histocompatibility complex, class II, DR beta 8 (pseudogene) Neighboring gene protein activator of interferon induced protein kinase EIF2AK2 pseudogene 1

    Genomic regions, transcripts, and products

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    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 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 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 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 Nef-triggered MHCII endocytosis requires Rab5 activity and lyst function, whereas lysosomal trafficking of internalized MHCII molecules requires Rab7 activity PubMed
    Pr55(Gag) 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
    gag In human macrophages, HIV-1 Gag proteins co-localize with MHC II (HLA-DR), CD63, and Lamp1 in MHC II compartments 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MHC class II protein complex binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables peptide antigen binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in peptide antigen assembly with MHC class II protein complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of T cell activation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    located_in ER to Golgi transport vesicle membrane TAS
    Traceable Author Statement
    more info
     
    located_in Golgi membrane TAS
    Traceable Author Statement
    more info
     
    part_of MHC class II protein complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in clathrin-coated endocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    located_in endocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in late endosome membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in late endosome membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lumenal side of endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in lysosomal membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lysosomal membrane TAS
    Traceable Author Statement
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in trans-Golgi network membrane TAS
    Traceable Author Statement
    more info
     
    located_in transport vesicle membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    major histocompatibility complex, class II, DR beta 4
    Names
    HLA class II histocompatibility antigen, DR beta 4 chain
    MHC class II antigen DRB4

    NCBI Reference Sequences (RefSeq)

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    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_021983.5NP_068818.4  major histocompatibility complex, class II, DR beta 4 precursor

      See identical proteins and their annotated locations for NP_068818.4

      Status: REVIEWED

      Source sequence(s)
      CR788250
      UniProtKB/Swiss-Prot
      B0S863, O78042, P13762, P79664, Q29889, Q30163, Q6TLK6, Q860N4, Q861F3, Q8WLT9, Q9BS54
      UniProtKB/TrEMBL
      A0A0G2JJQ8, A0A2K9UW88, A0A2K9UW93, A0A4D6PEG8, A0A5B9QYR3, Q2LIR4, X5D2U9
      Conserved Domains (2) summary
      pfam00969
      Location:42116
      MHC_II_beta; Class II histocompatibility antigen, beta domain
      cd21000
      Location:123218
      IgC1_MHC_II_beta_HLA-DR; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

      Range
      3840427..3855395 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330587.1XP_054186562.1  major histocompatibility complex, class II, DR beta 4 isoform X3

    2. XM_054330585.1XP_054186560.1  major histocompatibility complex, class II, DR beta 4 isoform X1

    3. XM_054330586.1XP_054186561.1  major histocompatibility complex, class II, DR beta 4 isoform X2

    4. XM_054330588.1XP_054186563.1  major histocompatibility complex, class II, DR beta 4 isoform X4

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      3876736..3891707 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330817.1XP_054186792.1  major histocompatibility complex, class II, DR beta 4 isoform X9

    2. XM_054330815.1XP_054186790.1  major histocompatibility complex, class II, DR beta 4 isoform X7

    3. XM_054330814.1XP_054186789.1  major histocompatibility complex, class II, DR beta 4 isoform X6

    4. XM_054330813.1XP_054186788.1  major histocompatibility complex, class II, DR beta 4 isoform X5

    5. XM_054330816.1XP_054186791.1  major histocompatibility complex, class II, DR beta 4 isoform X8

    RNA

    1. XR_008485704.1 RNA Sequence

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      3851133..3866104 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331329.1XP_054187304.1  major histocompatibility complex, class II, DR beta 4 isoform X14

    2. XM_054331327.1XP_054187302.1  major histocompatibility complex, class II, DR beta 4 isoform X12

    3. XM_054331325.1XP_054187300.1  major histocompatibility complex, class II, DR beta 4 isoform X10

    4. XM_054331326.1XP_054187301.1  major histocompatibility complex, class II, DR beta 4 isoform X11

    5. XM_054331328.1XP_054187303.1  major histocompatibility complex, class II, DR beta 4 isoform X13

    RNA

    1. XR_008485715.1 RNA Sequence