HLA-DRA major histocompatibility complex, class II, DR alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: HLA-DRAprovided by HGNC
Official Full Name: major histocompatibility complex, class II, DR alphaprovided by HGNC
Primary source: HGNC:HGNC:4947
See related: Ensembl:ENSG00000204287 MIM:142860; AllianceGenome:HGNC:4947
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: HLA-DRA1
Summary: HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]
Expression: Broad expression in lymph node (RPKM 921.6), lung (RPKM 809.6) and 24 other tissues See more
Orthologs: all
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Genomic context

Location:: 6p21.32

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (32439887..32445046)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (32292811..32297976)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (32407664..32412823)

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 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?

Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.
Title: Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.
Genetic polymorphism of HLA-DRA and alcohol consumption affect hepatitis development in the Korean population.
Title: Genetic polymorphism of HLA-DRA and alcohol consumption affect hepatitis development in the Korean population.
HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.
Title: HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.
Expression of NOTCH1, NOTCH4, HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion, immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer.
Title: Expression of NOTCH1, NOTCH4, HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion, immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer.
Identification of three novel HLA-DRA alleles by next-generation sequencing.
Title: Identification of three novel HLA-DRA alleles by next-generation sequencing.
Tri-SNP polymorphism in the intron of HLA-DRA1 affects type 1 diabetes susceptibility in the Finnish population.
Title: Tri-SNP polymorphism in the intron of HLA-DRA1 affects type 1 diabetes susceptibility in the Finnish population.
Combination of HLA-DR on Mycobacterium tuberculosis-Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection.
Title: Combination of HLA-DR on Mycobacterium tuberculosis-Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection.
The rs3129882/rs4248166 in HLA-DRA and rs34372695 in SYT11 are not associated with sporadic Parkinson's disease in Central Chinese population.
Title: The rs3129882/rs4248166 in HLA-DRA and rs34372695 in SYT11 are not associated with sporadic Parkinson's disease in Central Chinese population.
Shared Signature of Recent Positive Selection on the TSBP1-BTNL2-HLA-DRA Genes in Five Native Populations from North Borneo.
Title: Shared Signature of Recent Positive Selection on the TSBP1-BTNL2-HLA-DRA Genes in Five Native Populations from North Borneo.
Insights into the polymorphism in HLA-DRA and its evolutionary relationship with HLA haplotypes.
Title: Insights into the polymorphism in HLA-DRA and its evolutionary relationship with HLA haplotypes.

Submit: New GeneRIF Correction See all GeneRIFs (77)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia. EBI GWAS Catalog EBI GWAS CatalogPubMed
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
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. 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 and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. 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
Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a novel Parkinson's disease locus via stratified genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy. 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 genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles. EBI GWAS Catalog EBI GWAS CatalogPubMed
Risk alleles for multiple sclerosis identified by a genomewide study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. 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
Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. 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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Replication interactions

Interaction	Pubs
Clinical trophoblast microparticle samples from HIV-1 infected patients upregulates HLA-DR (MHC-II) expression on dendritic cells upon exposure	PubMed
HIV-1 infection upregulates HLA-DR (MHC-II) and CD38 on CD4+ and CD8+ T cells in clinical, patient samples	PubMed

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	Inhibition of CpG-B-induced maturation of plasmacytoid dendritic cells by HIV-1 gp120 results in downregulation of CD40, CD83, CCR7, and HLA-DR expression	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 cloned from subjects with early/acute progressive HIV infection downregulates HLA-DR in 721.221 cells to a greater extent relative to HIV-1 Nef cloned from subjects with chronic progressive infection	PubMed
	nef	Expression of patient-derived HIV-1 nef alleles downregulates MHC-II cell surface expression in activated CD4+ T cells	PubMed
	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	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
	nef	HIV-1 Nef-pulsed mDCs downregulate HLA-DR expression and upregulate CD25 and CCR7 expression in NK cells	PubMed
	nef	HIV-1 Nef expression inhibits MHC II presentation of viral antigens in infected antigen-presenting 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
Pr55(Gag)	gag	In human macrophages, HIV-1 Gag proteins co-localize with MHC II (HLA-DR), CD63, and Lamp1 in MHC II compartments	PubMed
	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
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

RH78783 (e-PCR)
- UniSTS:46610

PMC204479P1 (e-PCR)
- UniSTS:271940

GDB:177843 (e-PCR)
- UniSTS:154975

PMC153210P2 (e-PCR)
- UniSTS:271252

PMC87290P1 (e-PCR)
- UniSTS:273592

PMC166015P1 (e-PCR)
- UniSTS:271558

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MHC class II protein complex binding	HDA more info	PubMed
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 T cell receptor binding	IDA Inferred from Direct Assay 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 polysaccharide binding	IDA Inferred from Direct Assay 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 endogenous peptide antigen via MHC class II	IDA Inferred from Direct Assay more info	PubMed
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 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	IDA Inferred from Direct Assay more info	PubMed
involved_in cognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response	NAS Non-traceable Author Statement 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 peptide antigen assembly with MHC class II protein complex	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
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 cytotoxicity	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 positive regulation of memory T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of T-helper cell differentiation	IDA Inferred from Direct Assay 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	IDA Inferred from Direct Assay more info	PubMed
part_of MHC class II protein complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in autolysosome membrane	IEA Inferred from Electronic Annotation more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in immunological synapse	IDA Inferred from Direct Assay 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 lysosome	IDA Inferred from Direct Assay 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: HLA class II histocompatibility antigen, DR alpha chain

Names: MHC class II antigen DRA; histocompatibility antigen HLA-DR alpha

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_019111.5 → NP_061984.2 HLA class II histocompatibility antigen, DR alpha chain precursor

See identical proteins and their annotated locations for NP_061984.2

Status: REVIEWED

Source sequence(s)

BC032350, BC071659, BG548634, BM849755

Consensus CDS

CCDS4750.1

UniProtKB/Swiss-Prot

A2BET4, P01903, Q30160, Q6IAZ1, Q861I2, Q9TP70

UniProtKB/TrEMBL

A0A0G2JMH6, A0A1V0E3V4, B0UXD8

Related

ENSP00000378786.2, ENST00000395388.7

Conserved Domains (2) summary

pfam00993
Location:29 → 106

MHC_II_alpha; Class II histocompatibility antigen, alpha domain

cd21007
Location:110 → 204

IgC1_MHC_II_alpha_HLA-DR; Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains