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Aliases for HLA-DRA Gene

Aliases for HLA-DRA Gene

  • Major Histocompatibility Complex, Class II, DR Alpha 2 3
  • MHC Class II Antigen DRA 3 4
  • HLA-DRA1 3 4
  • HLA Class II Histocompatibility Antigen, DR Alpha Chain 3
  • Histocompatibility Antigen HLA-DR Alpha 3
  • MHC Cell Surface Glycoprotein 3
  • MLRW 3

External Ids for HLA-DRA Gene

Previous Symbols for HLA-DRA Gene

  • HLA-DRA1

Summaries for HLA-DRA Gene

Entrez Gene Summary for HLA-DRA 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. 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 (APC: B lymphocytes, dendritic cells, macrophages). 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, Jul 2008]

GeneCards Summary for HLA-DRA Gene

HLA-DRA (Major Histocompatibility Complex, Class II, DR Alpha) is a Protein Coding gene. Diseases associated with HLA-DRA include picardi-lassueur-little syndrome and mhc class ii deficiency. Among its related pathways are Class I MHC mediated antigen processing and presentation and GPCR Pathway. GO annotations related to this gene include MHC class II receptor activity. An important paralog of this gene is HLA-DMA.

UniProtKB/Swiss-Prot for HLA-DRA Gene

  • Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading

Gene Wiki entry for HLA-DRA Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HLA-DRA Gene

Genomics for HLA-DRA Gene

Genomic Location for HLA-DRA Gene

Start:
32,439,842 bp from pter
End:
32,445,046 bp from pter
Size:
5,205 bases
Orientation:
Plus strand

Genomic View for HLA-DRA Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HLA-DRA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Regulatory Elements for HLA-DRA Gene

Proteins for HLA-DRA Gene

  • Protein details for HLA-DRA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01903-DRA_HUMAN
    Recommended name:
    HLA class II histocompatibility antigen, DR alpha chain
    Protein Accession:
    P01903
    Secondary Accessions:
    • A2BET4
    • Q30160
    • Q6IAZ1
    • Q861I2
    • Q9TP70

    Protein attributes for HLA-DRA Gene

    Size:
    254 amino acids
    Molecular mass:
    28607 Da
    Quaternary structure:
    • Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.
    SequenceCaution:
    • Sequence=CAA25076.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HLA-DRA Gene

neXtProt entry for HLA-DRA Gene

Proteomics data for HLA-DRA Gene at MOPED

Post-translational modifications for HLA-DRA Gene

  • Ubiquitinated by MARCH1 or MARCH8 at Lys-244 leading to down-regulation of MHC class II. When associated with ubiquitination of the beta subunit of HLA-DR: HLA-DRB4 Lys-254, the down-regulation of MHC class II may be highly effective.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys244
  • Glycosylation at Asn143

Other Protein References for HLA-DRA Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for HLA-DRA Gene

Domains for HLA-DRA Gene

Gene Families for HLA-DRA Gene

HGNC:
  • C1SET :Immunoglobulin superfamily / C1-set domain containing
  • HLA :Histocompatibility complex

Graphical View of Domain Structure for InterPro Entry

P01903

UniProtKB/Swiss-Prot:

DRA_HUMAN
Domain:
  • Contains 1 Ig-like C1-type (immunoglobulin-like) domain.:
    • P01903
Family:
  • Belongs to the MHC class II family.:
    • P01903
genes like me logo Genes that share domains with HLA-DRA: view

Function for HLA-DRA Gene

Molecular function for HLA-DRA Gene

GENATLAS Biochemistry: HLA-DR,alpha chain
UniProtKB/Swiss-Prot Function: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading

Gene Ontology (GO) - Molecular Function for HLA-DRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding --
GO:0023026 MHC class II protein complex binding IDA 20458337
GO:0032395 MHC class II receptor activity NAS 6304715
GO:0042605 peptide antigen binding IDA 1448172
genes like me logo Genes that share ontologies with HLA-DRA: view

Phenotypes for HLA-DRA Gene

GenomeRNAi human phenotypes for HLA-DRA:
genes like me logo Genes that share phenotypes with HLA-DRA: view

No data available for Enzyme Numbers (IUBMB) , Animal Models , miRNA , Transcription Factor Targeting and HOMER Transcription for HLA-DRA Gene

Localization for HLA-DRA Gene

Subcellular locations from UniProtKB/Swiss-Prot for HLA-DRA Gene

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Late endosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HLA-DRA Gene COMPARTMENTS Subcellular localization image for HLA-DRA gene
Compartment Confidence
endoplasmic reticulum 5
endosome 5
lysosome 5
plasma membrane 5
vacuole 5
golgi apparatus 4
extracellular 3

Gene Ontology (GO) - Cellular Components for HLA-DRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005764 lysosome IDA 8890155
GO:0005765 lysosomal membrane TAS --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane NAS 6304715
genes like me logo Genes that share ontologies with HLA-DRA: view

Pathways for HLA-DRA Gene

genes like me logo Genes that share pathways with HLA-DRA: view

Gene Ontology (GO) - Biological Process for HLA-DRA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002503 peptide antigen assembly with MHC class II protein complex IDA 1448172
GO:0002504 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II IDA 21502329
GO:0002506 polysaccharide assembly with MHC class II protein complex IDA 21502329
GO:0006955 immune response NAS 6304715
GO:0019221 cytokine-mediated signaling pathway TAS --
genes like me logo Genes that share ontologies with HLA-DRA: view

Compounds for HLA-DRA Gene

(1) Novoseek inferred chemical compound relationships for HLA-DRA Gene

Compound -log(P) Hits PubMed IDs
chloramphenicol 10.9 1
genes like me logo Genes that share compounds with HLA-DRA: view

Transcripts for HLA-DRA Gene

mRNA/cDNA for HLA-DRA Gene

(1) REFSEQ mRNAs :
(18) Additional mRNA sequences :
(17) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HLA-DRA Gene

Major histocompatibility complex, class II, DR alpha:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HLA-DRA Gene

No ASD Table

Relevant External Links for HLA-DRA Gene

GeneLoc Exon Structure for
HLA-DRA
ECgene alternative splicing isoforms for
HLA-DRA

Expression for HLA-DRA Gene

mRNA expression in normal human tissues for HLA-DRA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HLA-DRA Gene

This gene is overexpressed in Whole Blood (5.0) and Spleen (4.4).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for HLA-DRA Gene

SOURCE GeneReport for Unigene cluster for HLA-DRA Gene Hs.520048

genes like me logo Genes that share expressions with HLA-DRA: view

No data available for mRNA Expression by UniProt/SwissProt for HLA-DRA Gene

Orthologs for HLA-DRA Gene

This gene was present in the common ancestor of chordates.

Orthologs for HLA-DRA Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PATR-DRA 35
  • 98.95 (n)
  • 98.82 (a)
PATR-DRA 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia BOLA-DRA 35
  • 85.24 (n)
  • 81.03 (a)
BOLA-DRA 36
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia DLA-DRA 35
  • 89.5 (n)
  • 87.01 (a)
DLA-DRA1 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia H2-Ea-ps 35
  • 76.75 (n)
  • 73.11 (a)
H2-Ea-ps 16
oppossum
(Monodelphis domestica)
Mammalia HLA-DRA 36
  • 68 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia oan-mir-1342 36
  • 63 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia RT1-Da 35
  • 79.28 (n)
  • 77.29 (a)
chicken
(Gallus gallus)
Aves BLA 35
  • 57.82 (n)
  • 50.44 (a)
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 55 (a)
ManyToMany
-- 36
  • 53 (a)
ManyToMany
zebrafish
(Danio rerio)
Actinopterygii zgc:123107 36
  • 30 (a)
ManyToMany
Species with no ortholog for HLA-DRA:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HLA-DRA Gene

ENSEMBL:
Gene Tree for HLA-DRA (if available)
TreeFam:
Gene Tree for HLA-DRA (if available)

Paralogs for HLA-DRA Gene

genes like me logo Genes that share paralogs with HLA-DRA: view

Variants for HLA-DRA Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HLA-DRA Gene

P01903-DRA_HUMAN
Genetic variations in HLA-DRA influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]

Sequence variations from dbSNP and Humsavar for HLA-DRA Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs7192 - 32,443,869(+) AGGGA(G/T)TGCGC missense, reference
rs7194 -- 32,444,703(+) TAATG(A/G)CTTTA utr-variant-3-prime
rs7195 -- 32,444,762(+) TCAGC(A/G)TTTTC utr-variant-3-prime
rs7196 -- 32,444,794(+) TGTGG(A/T)TATGC utr-variant-3-prime
rs7197 -- 32,444,803(+) GCCTC(C/G/T)TCGAT utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for HLA-DRA Gene

Variant ID Type Subtype PubMed ID
nsv830630 CNV Loss 17160897
dgv1930e1 CNV Complex 17122850
dgv1931e1 CNV Complex 17122850
nsv428142 CNV Gain+Loss 18775914
nsv830631 CNV Gain 17160897
dgv1932e1 CNV Complex 17122850
esv21985 CNV Gain+Loss 19812545
esv33476 CNV Gain+Loss 17666407

Relevant External Links for HLA-DRA Gene

HapMap Linkage Disequilibrium report
HLA-DRA
Human Gene Mutation Database (HGMD)
HLA-DRA
Locus Specific Mutation Databases (LSDB)
HLA-DRA

Disorders for HLA-DRA Gene

(6) Novoseek inferred disease relationships for HLA-DRA Gene

Disease -log(P) Hits PubMed IDs
carcinoma non-small cell lung 45.7 1
retinoblastoma 45.5 2
necrosis 0 1
tumors 0 5
lymphoma 0 1

Relevant External Links for HLA-DRA

Genetic Association Database (GAD)
HLA-DRA
Human Genome Epidemiology (HuGE) Navigator
HLA-DRA
genes like me logo Genes that share disorders with HLA-DRA: view

No data available for UniProtKB/Swiss-Prot for HLA-DRA Gene

Publications for HLA-DRA Gene

  1. The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes. (PMID: 12445311) Kralovicova J. … Vorechovsky I. (Tissue Antigens 2002) 3 4 23
  2. Oct-1 maintains an intermediate, stable state of HLA-DRA promoter repression in Rb-defective cells: an Oct-1-containing repressosome that prevents NF-Y binding to the HLA-DRA promoter. (PMID: 15105429) Osborne A.R. … Blanck G. (J. Biol. Chem. 2004) 3 23
  3. Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. (PMID: 2212658) Koppelman B. … Cresswell P. (J. Immunol. 1990) 3 4
  4. Structure and nucleotide sequence of the heavy chain gene of HLA- DR. (PMID: 6304715) Das H.K. … Weissman S.M. (Proc. Natl. Acad. Sci. U.S.A. 1983) 3 4
  5. Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. (PMID: 6324094) Schamboeck A. … Strominger J.L. (Nucleic Acids Res. 1983) 3 4

Products for HLA-DRA Gene

Sources for HLA-DRA Gene

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