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

Gene ID: 3126, updated on 12-Apr-2014
Official Symbol
HLA-DRB4provided by HGNC
Official Full Name
major histocompatibility complex, class II, DR beta 4provided by HGNC
Primary source
HGNC:4952
Locus tag
DAMC-146E17.2
See related
HPRD:09986
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; DR-4; DRB4; HLA-DR4B
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 (APC: B lymphocytes, dendritic cells, macrophages). 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. DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. The presence of DRB4 is linked with allelic variants of DRB1, otherwise it is omitted. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [provided by RefSeq, Jul 2008]
Annotation information
Annotation category: only annotated on alternate loci in reference assembly
Location :
6p21.3
See HLA-DRB4 in MapViewer

NT_167246.2Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102725030 Neighboring gene butyrophilin-like 2 (MHC class II associated) Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene protein FAM136A-like Neighboring gene protein kinase, interferon-inducible double stranded RNA dependent activator pseudogene 1

NT_167247.2Genomic Context describing neighboring genes Neighboring gene butyrophilin-like 2 (MHC class II associated) Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene major histocompatibility complex, class II, DQ alpha 1 Neighboring gene major histocompatibility complex, class II, DQ beta 1

NT_167249.2Genomic Context describing neighboring genes Neighboring gene butyrophilin-like 2 (MHC class II associated) Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene major histocompatibility complex, class II, DR beta 8 (pseudogene) Neighboring gene protein kinase, interferon-inducible double stranded RNA dependent activator pseudogene 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein 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 surface glycoprotein gp120 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 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
Gag, Pr55 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 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 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 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
Nef, p27 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
Tat, p14 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, p16 vpu HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells PubMed
capsid 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 Protein Interaction Database

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  • Antigen processing and presentation, organism-specific biosystem (from KEGG)
    Antigen processing and presentation, organism-specific biosystem
    Antigen processing and presentation
  • Antigen processing and presentation, conserved biosystem (from KEGG)
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    Antigen processing and presentation
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  • Herpes simplex infection, organism-specific biosystem (from KEGG)
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  • Herpes simplex infection, conserved biosystem (from KEGG)
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  • Immune System, organism-specific biosystem (from REACTOME)
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  • Inflammatory bowel disease (IBD), organism-specific biosystem (from KEGG)
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  • Influenza A, organism-specific biosystem (from KEGG)
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
MHC class II receptor activity TAS
Traceable Author Statement
more info
PubMed 
peptide antigen binding ISS
Inferred from Sequence or Structural Similarity
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
T cell costimulation TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
T-helper 1 type immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
antigen processing and presentation of exogenous peptide antigen via MHC class II TAS
Traceable Author Statement
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
detection of bacterium ISS
Inferred from Sequence or Structural Similarity
more info
 
humoral immune response mediated by circulating immunoglobulin ISS
Inferred from Sequence or Structural Similarity
more info
 
immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
immunoglobulin production involved in immunoglobulin mediated immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
inflammatory response to antigenic stimulus IDA
Inferred from Direct Assay
more info
PubMed 
interferon-gamma-mediated signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of T cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of inflammatory response to antigenic stimulus IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of interferon-gamma production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of insulin secretion involved in cellular response to glucose stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
protein tetramerization ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of interleukin-10 secretion ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of interleukin-4 production ISS
Inferred from Sequence or Structural Similarity
more info
 
signal transduction NAS
Non-traceable Author Statement
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 IEA
Inferred from Electronic Annotation
more info
 
clathrin-coated endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
external side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
integral component of lumenal side of endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
integral component of plasma membrane TAS
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
 
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
 
Preferred Names
major histocompatibility complex, class II, DR beta 4
Names
major histocompatibility complex, class II, DR beta 4
leukocyte antigen
MHC class2 antigen
MHC HLA DR-beta chain
MHC class II antigen DRB4
DRB1 transplantation antigen
human leucocyte antigen DRB4
MHC class II antigen HLA-DR-beta
HLA class II histocompatibility antigen, DR beta 4 chain

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.

Genomic

  1. NG_002433.1 Reference

    Range
    3612..18584, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_021983.4NP_068818.4  major histocompatibility complex, class II, DR beta 4 precursor

    See proteins identical to NP_068818.4

    Status: REVIEWED

    Source sequence(s)
    AI829825, BC005312, BF974249
    UniProtKB/Swiss-Prot
    P13762
    Conserved Domains (2) summary
    cd05766
    Location:126219
    Blast Score: 394
    IgC_MHC_II_beta; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain
    pfam00969
    Location:43116
    Blast Score: 398
    MHC_II_beta; Class II histocompatibility antigen, beta domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2

    Range
    3840424..3855395, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_247369.2 RNA Sequence

Reference GRCh38 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2

    Range
    3876733..3891705, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006725948.1XP_006726011.1  

    Conserved Domains (2) summary
    cd05766
    Location:126219
    Blast Score: 394
    IgC_MHC_II_beta; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain
    pfam00969
    Location:43116
    Blast Score: 398
    MHC_II_beta; Class II histocompatibility antigen, beta domain

RNA

  1. XR_247388.2 RNA Sequence

Reference GRCh38 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2

    Range
    3851130..3866104, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_247422.2 RNA Sequence

Alternate HuRef

Genomic

  1. NW_001841135.1 Alternate HuRef

    Range
    19392..24258, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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