HLA-DRA

Protein identityUniProt · HPA

UniProt accession

P01903

Gene

HLA-DRA

Ensembl

ENSG00000204287

Chromosome

6

Canonical length

254 aa

Protein class

Plasma proteins, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

254 residues, UniProt reviewed canonical sequence.

>P01903|HLA-DRA
     1  MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD
    61  MAKKETVWRL EEFGRFASFE AQGALANIAV DKANLEIMTK RSNYTPITNV PPEVTVLTNS
   121  PVELREPNVL ICFIDKFTPP VVNVTWLRNG KPVTTGVSET VFLPREDHLF RKFHYLPFLP
   181  STEDVYDCRV EHWGLDEPLL KHWEFDAPSP LPETTENVVC ALGLTVGLVG IIIGTIFIIK
   241  GLRKSNAAER RGPL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HLA-DRA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

1,197 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HLA-DRA.

Disease | ImmuneIEDB

Conditions an epitope on HLA-DRA was assayed in.

• multiple sclerosis T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.59

gnomAD pLI

0.52

gnomAD missense Z

1.17

DepMap mean gene effect

0.08

DepMap dependency class

selective

OntologyGO

Biological processes

• adaptive immune response
• antigen processing and presentation of endogenous peptide antigen via MHC class II
• antigen processing and presentation of exogenous peptide antigen via MHC class II
• cognition
• immune response
• myeloid dendritic cell antigen processing and presentation
• peptide antigen assembly with MHC class II protein complex
• positive regulation of CD4-positive, alpha-beta T cell activation
• positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation
• positive regulation of immune response
• positive regulation of memory T cell differentiation
• positive regulation of T cell activation
• positive regulation of T cell mediated cytotoxicity
• regulation of T-helper cell differentiation
• antigen processing and presentation of peptide or polysaccharide antigen via MHC class II

Molecular functions

• MHC class II protein complex binding
• peptide antigen binding
• polysaccharide binding
• T cell receptor binding

Cellular components

• autolysosome membrane
• cell surface
• clathrin-coated endocytic vesicle membrane
• early endosome membrane
• endocytic vesicle membrane
• ER to Golgi transport vesicle membrane
• extracellular exosome
• Golgi membrane
• immunological synapse
• late endosome membrane
• lumenal side of endoplasmic reticulum membrane
• lysosomal membrane
• lysosome
• MHC class II protein complex
• plasma membrane
• trans-Golgi network membrane
• transport vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• MHC class II, alpha chain, N-terminal
• Immunoglobulin/major histocompatibility complex, conserved site
• Immunoglobulin C1-set
• Immunoglobulin-like domain
• MHC classes I/II-like antigen recognition protein
• Immunoglobulin-like fold
• MHC class II, alpha/beta chain, N-terminal
• Immunoglobulin-like domain superfamily
• Major Histocompatibility Complex/Immunoglobulin
• Class II histocompatibility antigen, alpha domain
• Immunoglobulin C1-set domain

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Cytoplasmic vesicle
• Disulfide bond
• Endoplasmic reticulum
• Endosome
• Glycoprotein
• Host-virus interaction
• Immunity
• Isopeptide bond
• Lysosome
• Membrane
• MHC II
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of HLA-DRA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HLA-DMB