HLA-DRB5 major histocompatibility complex, class II, DR beta 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HLA-DRB5provided by HGNC
Official Full Name: major histocompatibility complex, class II, DR beta 5provided by HGNC
Primary source: HGNC:HGNC:4953
See related: Ensembl:ENSG00000198502 MIM:604776; AllianceGenome:HGNC:4953
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: DRB5; HLA-DRB5*
Summary: HLA-DRB5 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]
Expression: Broad expression in lung (RPKM 275.5), lymph node (RPKM 163.3) and 14 other tissues See more
Orthologs: all
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Genomic context

Location:: 6p21.32

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (32517353..32530287, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (32485130..32498064, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HLA DRB5 *01:01 is associated with pruritus in individuals with Fitzpatrick skin type IV-VI.
Title: HLA DRB5∗01:01 is associated with pruritus in individuals with Fitzpatrick skin type IV-VI.
Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis.
Title: Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis.
Whole Exome Sequencing Identified Two Single Nucleotide Polymorphisms of Human Leukocyte Antigen-DRB5 in Familial Sarcoidosis in China.
Title: Whole Exome Sequencing Identified Two Single Nucleotide Polymorphisms of Human Leukocyte Antigen-DRB5 in Familial Sarcoidosis in China.
Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15.
Title: Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15.
Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia.
Title: Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia.
In this study, molecular dynamics simulation was performed on the complexes of Top1 peptide with various HLA-DR subtypes divided into ATASSc-associated alleles (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), suspected allele (HLA-DRB5*01:02), and non-associated allele (HLA-DRB1*01:01).
Title: Interactions of HLA-DR and Topoisomerase I Epitope Modulated Genetic Risk for Systemic Sclerosis.
Variation at HLA-DRB5 being associated both with Parkinson's disease and Alzheimer's disease, ariation at HLA-DRB5 being associated both with Parkinson's disease and Alzheimer's disease.
Title: Genetic variation associated with the occurrence and progression of neurological disorders.
Case-control study in Han Chinese from the southwest of the country suggests that risk of ALS is increased by the AA genotype at rs9268856 in the HLA-DRA/HLA-DRB5 gene, but not by the SNPs rs9268877 in HLA-DRA/HLA-DRB5, rs1980493 in BTNL2 or rs302668 in RAB38/CTSC
Title: HLA-DRA/HLA-DRB5 polymorphism affects risk of sporadic ALS and survival in a southwest Chinese cohort.
This study identified genetic overlap between Alzheimer disease and immune-mediated diseases, implicating the HLA locus and IPMK in the pathobiology of Alzheimer disease.
Title: Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease.
HLA-DRB5 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.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
An association between anti-nuclear antibody and HLA class II locus and heterogeneous characteristics of staining patterns: The Nagahama Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Frontotemporal dementia and its subtypes: a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

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	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
	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
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	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	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	In human macrophages, HIV-1 Gag proteins co-localize with MHC II (HLA-DR), CD63, and Lamp1 in MHC II compartments	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	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	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

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

RH69092 (e-PCR)
- UniSTS:86556

RH80065 (e-PCR)
- UniSTS:88606

RH46825 (e-PCR)
- UniSTS:24120

NoName (e-PCR)
- UniSTS:487006

RH79846 (e-PCR)
- UniSTS:85123

RH80804 (e-PCR)
- UniSTS:85967

RH76259 (e-PCR)
- UniSTS:83922

RH15772 (e-PCR)
- UniSTS:7126

RH69091 (e-PCR)
- UniSTS:25841

RH80800 (e-PCR)
- UniSTS:92913

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
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 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
part_of MHC class II protein complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
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

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Preferred Names: major histocompatibility complex, class II, DR beta 5

Names: DR beta-5; HLA class II histocompatibility antigen, DR-5 beta chain; MHC class II antigen DRB5

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)

NM_002125.4 → NP_002116.2 major histocompatibility complex, class II, DR beta 5 precursor

See identical proteins and their annotated locations for NP_002116.2

Status: REVIEWED

Source sequence(s)

AL713966

Consensus CDS

CCDS4751.1

UniProtKB/Swiss-Prot

B2RBV6, C7C4X3, O00157, O00283, O46700, Q29703, Q29787, Q29788, Q30126, Q30150, Q30154, Q30199, Q6SJR2, Q7M2H9, Q8HWS7, Q8WLR5, Q9MY54, Q9XRX6

UniProtKB/TrEMBL

A0A2Z4LKS3, A0A4D6PFE0

Related

ENSP00000364114.3, ENST00000374975.4

Conserved Domains (2) summary

pfam00969
Location:42 → 116

MHC_II_beta; Class II histocompatibility antigen, beta domain

cd21000
Location:123 → 218

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 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

32517353..32530287 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011514562.3 → XP_011512864.1 major histocompatibility complex, class II, DR beta 5 isoform X1

UniProtKB/TrEMBL

A0A4D6PFE0

Conserved Domains (2) summary

cd05766
Location:126 → 219

IgC_MHC_II_beta; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain

pfam00969
Location:42 → 116

MHC_II_beta; Class II histocompatibility antigen, beta domain