HLA-DRB3 major histocompatibility complex, class II, DR beta 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HLA-DRB3provided by HGNC
Official Full Name: major histocompatibility complex, class II, DR beta 3provided by HGNC
Primary source: HGNC:HGNC:4951
See related: MIM:612735; AllianceGenome:HGNC:4951
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DRB3; HLA-DPB1; HLA-DR1B; HLA-DR3B; HLA-DRB3*
Summary: HLA-DRB3 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

Location:: 6p21.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6 (ALT_REF_LOCI_2)	NT_113891.3 (3934018..3947156, complement)
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6 (ALT_REF_LOCI_1)	NT_167244.2 (3824508..3837642, complement)
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6 (ALT_REF_LOCI_6)	NT_167248.2 (3715352..3728489, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (32345227..32358367, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6 Unlocalized Scaffold (ALT_REF_LOCI_2)	NT_113891.2 (3934124..3947262, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6 Unlocalized Scaffold (ALT_REF_LOCI_1)	NT_167244.1 (3774424..3787558, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6 Unlocalized Scaffold (ALT_REF_LOCI_6)	NT_167248.1 (3720948..3734085, complement)

NT_167244.2 Genomic Context describing neighboring genes

NT_113891.3 Genomic Context describing neighboring genes

NT_167248.2 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Full genomic sequence of the HLA-DRB3*02:32 allele by Single Molecule Real-time Sequencing Technology.
Title: Full genomic sequence of the HLA-DRB3*02:32 allele by Single Molecule Real-time Sequencing Technology.
Characterization of the novel HLA-DRB3*02:02:25 allele by sequencing-based typing.
Title: Characterization of the novel HLA-DRB3*02:02:25 allele by sequencing-based typing.
Characterization of the novel HLA-DRB3*03:49 allele by sequencing-based typing.
Title: Characterization of the novel HLA-DRB3*03:49 allele by sequencing-based typing.
In contrast to HLA-DRB4*01:01P, the inheritance of HLA-DRB3*01:01 is strongly associated with the propensity for mounting a humoral immune response against fetal HPA-1a antigen.
Title: HLA-DRB3*01:01 is a predictor of immunization against human platelet antigen-1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia.
our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with phospholipase A2 receptor related idiopathic membranous nephropathy in the Chinese population
Title: HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy.
The first time that the haplotypes A33-DR3 and A33-DR9 were found with an enhanced predisposition to type 1 diabetes in Han Chinese.
Title: HLA-A*33-DR3 and A*33-DR9 haplotypes enhance the risk of type 1 diabetes in Han Chinese.
HLA-DRB3 affects type 1 diabetes risk and islet autoantibodies.
Title: Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes.
this mouse model unravels a critical role for HLA-DR3 in generating an autoimmune response to SmD and lupus nephritis in the NZM2328 background.
Title: A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus.
Haplotyping was done on 91 Southern Europe celiac patients. HLA-DR3-DQ2 without HLA-DR7-DQ2 was present in 62.6%, HLA-DR7-DQ2 without HLA-DR3-DQ2 was present in 16.5% and HLA-DR4-DQ8 without HLA-DQ2 was present in 3.3%.
Title: Paediatric celiac patients carrying the HLA-DR7-DQ2 and HLA-DR3-DQ2 haplotypes display small clinical differences.
Children with the HLA haplotype DR3-DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood.
Title: Risk of pediatric celiac disease according to HLA haplotype and country.

Submit: New GeneRIF Correction See all GeneRIFs (46)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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 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	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	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 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 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 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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:177509 (e-PCR)
- UniSTS:154904

RH69063 (e-PCR)
- UniSTS:91672

RH69092 (e-PCR)
- UniSTS:86556

RH80065 (e-PCR)
- UniSTS:88606

RH69107 (e-PCR)
- UniSTS:85025

RH46825 (e-PCR)
- UniSTS:24120

STS-V00522 (e-PCR)
- UniSTS:68941

NoName (e-PCR)
- UniSTS:487006

RH79846 (e-PCR)
- UniSTS:85123

RH46799 (e-PCR)
- UniSTS:54689

RH15772 (e-PCR)
- UniSTS:7126

RH69091 (e-PCR)
- UniSTS:25841

RH80800 (e-PCR)
- UniSTS:92913

RH70404 (e-PCR)
- UniSTS:86775

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 MHC class II receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables peptide antigen binding	IBA Inferred from Biological aspect of Ancestor more info
enables peptide antigen binding	IDA Inferred from Direct Assay more info	PubMed
enables peptide antigen binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
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 antigen processing and presentation of exogenous peptide antigen via MHC class II	IDA Inferred from Direct Assay more info	PubMed
involved_in myeloid dendritic cell antigen processing and presentation	IDA Inferred from Direct Assay more info	PubMed
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 CD4-positive, alpha-beta T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of T cell mediated immune response to tumor cell	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

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
part_of MHC class II protein complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in autolysosome membrane	IEA Inferred from Electronic Annotation 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 membrane	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
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

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Preferred Names: major histocompatibility complex, class II, DR beta 3

Names: HLA DRB3; HLA class II histocompatibility antigen, DR beta 3 chain; MHC class II DR beta chain; MHC class II HLA-DR beta 3 chain; MHC class II antigen DR beta 3 chain; MHC class II antigen DRB3; MHC class II protein; human leucocyte antigen DRB3; major histocompatibility complex, class II, DRB3

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.