HLA-DMB major histocompatibility complex, class II, DM beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: HLA-DMBprovided by HGNC
Official Full Name: major histocompatibility complex, class II, DM betaprovided by HGNC
Primary source: HGNC:HGNC:4935
See related: Ensembl:ENSG00000242574 MIM:142856; AllianceGenome:HGNC:4935
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: RING7; D6S221E
Summary: HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. 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. [provided by RefSeq, Jul 2008]
Expression: Broad expression in lymph node (RPKM 104.0), spleen (RPKM 76.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.32

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (32934636..32941028, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (32755985..32762378, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (32902413..32908805, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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-DMB alleles and haplotypes in Ecuador (Cuenca) Amerindians: Importance for HLA and disease studies.
Title: HLA-DMB alleles and haplotypes in Ecuador (Cuenca) Amerindians: Importance for HLA and disease studies.
This study provides novel insights into how HLA-DM efficiently catalyzes peptide loading during antigen presentation.
Title: Evaluating the Role of HLA-DM in MHC Class II-Peptide Association Reactions.
Data suggest that antigen processing by MHC class II HLA-DMB antigen is a target pathway in the pathogenesis of HIV-related Kaposi's sarcoma.
Title: SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma.
The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove.
Title: Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection.
DMA*01:01 (69.35%) and DMB*01:01 (52.5%) alleles were more frequent in Chinese Hans
Title: Analysis of HLA-DM polymorphisms in the Chinese Han population.
Overexpression of HLA-DM at the plasma membrane of dendritic cells improves quantitatively, but also qualitatively, the presentation of CD4-expressing T cell epitopes in cellular vaccine therapies for cancer.
Title: Forced expression of HLA-DM at the surface of dendritic cells increases loading of synthetic peptides on MHC class II molecules and modulates T cell responses.
Multiple mechanisms, operating along the biosynthetic pathway of class II molecules, contribute to DM-mediated increases in the abundance of low-CLIP-affinity alleles.
Title: DM influences the abundance of major histocompatibility complex class II alleles with low affinity for class II-associated invariant chain peptides via multiple mechanisms.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
HLA-DM mediates a noncooperative release of prebound influenza virus hemagglutinin peptides from wild-type HLA-DR1 by destabilizing the beta81 hydrogen (H-)bond, since a similar phenomenon is observed when this H-bond is absent.
Title: Cutting edge: HLA-DM-mediated peptide exchange functions normally on MHC class II-peptide complexes that have been weakened by elimination of a conserved hydrogen bond.
No individual component of conserved HLA-DM hydrogen bond network demonstrates an essential role in the DM catalytic mechanism. Catalytic potency of HLA-DM with each beta-chain mutant was equal to or greater than that observed with wild-type HLA-DR1.
Title: Cutting edge: HLA-DM functions through a mechanism that does not require specific conserved hydrogen bonds in class II MHC-peptide complexes.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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

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	HIV envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Ag	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
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	Expression of patient-derived HIV-1 nef alleles downregulates MHC-II cell surface expression in activated CD4+ T cells	PubMed
	nef	HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules	PubMed
	nef	HIV-1 Nef expression inhibits MHC II presentation of viral antigens in infected antigen-presenting 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	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
Tat	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

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

SHGC-143932 (e-PCR)
- UniSTS:172102

D6S2091 (e-PCR)
- UniSTS:10062

PMC316580P3 (e-PCR)
- UniSTS:273010

RH12803 (e-PCR)
- UniSTS:2470

SHGC-144492 (e-PCR)
- UniSTS:172270

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 protein complex binding	IDA Inferred from Direct Assay more info	PubMed
enables peptide antigen binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in MHC class II protein complex assembly	IMP Inferred from Mutant Phenotype 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	IMP Inferred from Mutant Phenotype 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 peptide antigen assembly with MHC class II protein complex	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 activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of MHC class II protein complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MHC class II protein complex	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay 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
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

General protein information

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Preferred Names: HLA class II histocompatibility antigen, DM beta chain

Names: MHC class II HLA-DMB; MHC class II antigen DMB; MHC class II antigen HLA-DM beta chain; class II histocompatibility antigen, M beta chain; really interesting new gene 7 protein

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_002118.5 → NP_002109.2 HLA class II histocompatibility antigen, DM beta chain precursor

See identical proteins and their annotated locations for NP_002109.2

Status: REVIEWED

Source sequence(s)

CD742571, EL948395, U15085

Consensus CDS

CCDS4760.1

UniProtKB/Swiss-Prot

O77936, P28068, Q13012, Q29751, Q58ZE2, Q5SNZ8, Q5STC4, Q9XRX2

UniProtKB/TrEMBL

A0A1V0E3P2, X5CKA5

Related

ENSP00000398890.2, ENST00000418107.3

Conserved Domains (2) summary

cd05766
Location:115 → 209

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

pfam00969
Location:27 → 106

MHC_II_beta; Class II histocompatibility antigen, beta domain