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

Gene ID: 3126, updated on 2-Nov-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
See related
AllianceGenome: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_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_4) NT_167246.2 (3840427..3855395, complement)
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_5) NT_167247.2 (3876736..3891707, complement)
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 (ALT_REF_LOCI_7) NT_167249.2 (3851133..3866104, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_4) NT_167246.1 (3846055..3861007, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_5) NT_167247.1 (3882329..3897284, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 Unlocalized Scaffold (ALT_REF_LOCI_7) NT_167249.1 (3850439..3865394, 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_2024_08

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