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P01903 (DRA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
HLA class II histocompatibility antigen, DR alpha chain
Alternative name(s):
MHC class II antigen DRA
Gene names
Name:HLA-DRA
Synonyms:HLA-DRA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subunit 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. Ref.31 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatustrans-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. Ref.22 Ref.25

Post-translational modification

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. Ref.25

Polymorphism

The following alleles of DRA are known: DRA*01:01 and DRA*01:02. The sequence shown is that of DRA*01:01.

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

Sequence similarities

Belongs to the MHC class II family.

Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Sequence caution

The sequence CAA25076.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCell membrane
Endoplasmic reticulum
Endosome
Golgi apparatus
Lysosome
Membrane
MHC II
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processT cell costimulation

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

antigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

antigen processing and presentation of peptide or polysaccharide antigen via MHC class II

Inferred from direct assay PubMed 21502329. Source: UniProt

cognition

Inferred from mutant phenotype PubMed 23227193. Source: UniProt

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

immune response

Non-traceable author statement Ref.4Ref.13. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

peptide antigen assembly with MHC class II protein complex

Inferred from direct assay PubMed 1448172PubMed 22733780PubMed 7606781. Source: UniProt

polysaccharide assembly with MHC class II protein complex

Inferred from direct assay PubMed 21502329. Source: UniProt

   Cellular_componentER to Golgi transport vesicle membrane

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement. Source: Reactome

MHC class II protein complex

Inferred from direct assay PubMed 1448172PubMed 21502329PubMed 22733780Ref.31PubMed 7606781. Source: UniProt

cell surface

Inferred from direct assay PubMed 21502329. Source: UniProt

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 11487543PubMed 12519789PubMed 19056867PubMed 19199708PubMed 20458337PubMed 23376485. Source: UniProt

integral component of lumenal side of endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Non-traceable author statement Ref.4Ref.13. Source: UniProtKB

late endosome membrane

Inferred from direct assay Ref.22Ref.25. Source: UniProtKB

lysosomal membrane

Inferred from direct assay Ref.22. Source: UniProtKB

lysosome

Inferred from direct assay PubMed 8890155. Source: MGI

plasma membrane

Inferred from direct assay PubMed 8890155. Source: MGI

trans-Golgi network membrane

Traceable author statement. Source: Reactome

transport vesicle membrane

Traceable author statement. Source: Reactome

   Molecular_functionMHC class II protein complex binding

Inferred from direct assay PubMed 20458337. Source: UniProt

MHC class II receptor activity

Non-traceable author statement Ref.4Ref.13. Source: UniProtKB

peptide antigen binding

Inferred from direct assay PubMed 1448172PubMed 21502329PubMed 22733780Ref.31PubMed 7606781. Source: UniProt

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Ref.11 Ref.12 Ref.13
Chain26 – 254229HLA class II histocompatibility antigen, DR alpha chain
PRO_0000018947

Regions

Topological domain26 – 216191Extracellular Potential
Transmembrane217 – 23923Helical; Potential
Topological domain240 – 25415Cytoplasmic Potential
Domain112 – 20493Ig-like C1-type
Region26 – 10984Alpha-1
Region110 – 20394Alpha-2
Region204 – 21613Connecting peptide

Amino acid modifications

Glycosylation1031N-linked (GlcNAc...) Ref.26 Ref.31
Glycosylation1431N-linked (GlcNAc...) Ref.26 Ref.31
Disulfide bond132 ↔ 188 Ref.31 Ref.35 Ref.36 Ref.37 Ref.38
Cross-link244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25

Natural variations

Natural variant161V → L.
Corresponds to variant rs16822586 [ dbSNP | Ensembl ].
VAR_035241
Natural variant2421V → L in allele DRA*01:02.
Corresponds to variant rs7192 [ dbSNP | Ensembl ].
VAR_004399

Experimental info

Mutagenesis2441K → R: Almost no change in down-regulation of MHC class II. No ubiquitination and complete loss of down-regulation of MHC class II; when associated with 'R-254' of HLA-DRB. Ref.25
Sequence conflict28 – 292EE → AD AA sequence Ref.13
Sequence conflict331I → T AA sequence Ref.13
Sequence conflict34 – 352QA → YP AA sequence Ref.13
Sequence conflict481M → Q AA sequence Ref.13
Sequence conflict541D → T AA sequence Ref.13
Sequence conflict591V → Y AA sequence Ref.12
Sequence conflict641K → L AA sequence Ref.12
Sequence conflict671V → A AA sequence Ref.11
Sequence conflict691R → L AA sequence Ref.12
Sequence conflict751R → P AA sequence Ref.12
Sequence conflict781S → D AA sequence Ref.12
Sequence conflict1491N → E AA sequence Ref.11

Secondary structure

................................. 254
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01903 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 3CD1CDBA952B2350

FASTA25428,607
        10         20         30         40         50         60 
MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD 

        70         80         90        100        110        120 
MAKKETVWRL EEFGRFASFE AQGALANIAV DKANLEIMTK RSNYTPITNV PPEVTVLTNS 

       130        140        150        160        170        180 
PVELREPNVL ICFIDKFTPP VVNVTWLRNG KPVTTGVSET VFLPREDHLF RKFHYLPFLP 

       190        200        210        220        230        240 
STEDVYDCRV EHWGLDEPLL KHWEFDAPSP LPETTENVVC ALGLTVGLVG IIIGTIFIIK 

       250 
GVRKSNAAER RGPL 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization of the corresponding gene."
Lee J.S., Trowsdale J., Travers P.J., Carey J., Grosveld F., Jenkins J., Bodmer W.F.
Nature 299:750-752(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRA*01:01).
[2]"Cloning the heavy chain of human HLA-DR antigen using synthetic oligodeoxyribonucleotides as hybridization probes."
Kajimura Y., Toyoda H., Sato M., Miyakoshi S., Kaplan S.A., Ike Y., Goyert S.M., Silver J., Hawke D., Shively J.E., Suggs S.V., Wallace R.B., Itakura K.
DNA 2:175-182(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRA*01:01).
[3]"Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain."
Schamboeck A., Korman A.J., Kamb A., Strominger J.L.
Nucleic Acids Res. 11:8663-8675(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DRA*01:02).
[4]"Structure and nucleotide sequence of the heavy chain gene of HLA-DR."
Das H.K., Lawrance S.K., Weissman S.M.
Proc. Natl. Acad. Sci. U.S.A. 80:3543-3547(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DRA*01:01).
[5]Erratum
Das H.K., Lawrance S.K., Weissman S.M.
Proc. Natl. Acad. Sci. U.S.A. 80:7024-7024(1983)
Cited for: SEQUENCE REVISION.
[6]"Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain."
Koppelman B., Cresswell P.
J. Immunol. 145:2730-2736(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRA*01:02).
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRA*01:01).
[8]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES DRA*01:01 AND DRA*01:02).
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DRA*01:01).
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELES DRA*01:01 AND DRA*01:02).
Tissue: Blood and Colon.
[11]"Primary structure of class II human histocompatibility antigens. 2nd Communication. Amino acid sequence of the N-terminal 179 residues of the alpha-chain of an HLA-Dw2/DR2 alloantigen."
Yang C.-Y., Kratzin H., Gotz H., Thinnes F.P., Kruse T., Egert G., Pauly E., Kolbel S., Wernet P., Hilschmann N.
Hoppe-Seyler's Z. Physiol. Chem. 363:671-676(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-204.
[12]"N-terminal amino acid sequences of the alpha and beta chains of HLA-DR1 and HLA-DR2 antigens."
Walker L.E., Hewick R., Hunkapiller M.W., Hood L.E., Dreyer W.J., Reisfeld R.A.
Biochemistry 22:185-188(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-94.
Tissue: B-cell.
[13]"Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins."
Larhammar D., Gustafsson K., Claesson L., Bill P., Wiman K., Schenning L., Sundelin J., Widmark E., Peterson P.A., Rask L.
Cell 30:153-161(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-60, NUCLEOTIDE SEQUENCE [MRNA] OF 32-202 AND 204-254.
[14]"The amino acid sequence and gene organization of the heavy chain of the HLA-DR antigen: homology to immunoglobulins."
Korman A.J., Auffray C., Schamboeck A., Strominger J.L.
Proc. Natl. Acad. Sci. U.S.A. 79:6013-6017(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-254 (ALLELE DRA*01:02).
[15]"The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes."
Kralovicova J., Marsh S.G., Waller M.J., Hammarstrom L., Vorechovsky I.
Tissue Antigens 60:266-267(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-254 (ALLELE DRA*01:02).
Tissue: Blood.
[16]"Heterozygote advantage for HLA class-II type in hepatitis B virus infection."
Thursz M.R., Thomas H.C., Greenwood B.M., Hill A.V.S.
Nat. Genet. 17:11-12(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION.
[17]Erratum
Thursz M.R., Thomas H.C., Greenwood B.M., Hill A.V.S.
Nat. Genet. 18:88-88(1998)
[18]"Invariant chain structure and MHC class II function."
Cresswell P.
Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[19]"Presentation of antigens by MHC class II molecules: getting the most out of them."
Villadangos J.A.
Mol. Immunol. 38:329-346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[20]"MHC class II molecules on the move for successful antigen presentation."
Rocha N., Neefjes J.
EMBO J. 27:1-5(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[21]"Autophagy in MHC class II presentation: sampling from within."
Menendez-Benito V., Neefjes J.
Immunity 26:1-3(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[22]"MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation."
De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P., Gatti E.
Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"MHC class II transport at a glance."
Berger A.C., Roche P.A.
J. Cell Sci. 122:1-4(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[24]"CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract."
Beswick E.J., Reyes V.E.
World J. Gastroenterol. 15:2855-2861(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[25]"The HLA-DRalpha chain is modified by polyubiquitination."
Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.
J. Biol. Chem. 284:7007-7016(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-244 BY MARCH1 AND MARCH8, MUTAGENESIS OF LYS-244, SUBCELLULAR LOCATION.
[26]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103 AND ASN-143.
Tissue: Liver.
[27]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1."
Brown J.H., Jardetzky T.S., Gorga J.C., Stern L.J., Urban R.G., Strominger J.L., Wiley D.C.
Nature 364:33-39(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-207.
[29]"Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide."
Stern L.J., Brown J.H., Jardetzky T.J., Gorga J.C., Urban R.G., Strominger J.L., Wiley D.C.
Nature 368:215-221(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-207.
[30]"Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen."
Jardetzky T.S., Brown J.H., Gorga J.C., Stern L.J., Urban R.G., Chi Y.I., Stauffacher C., Strominger J.L., Wiley D.C.
Nature 368:711-718(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF COMPLEX WITH SEB.
[31]"The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3."
Ghosh P., Amaya M., Mellins E., Wiley D.C.
Nature 378:457-462(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 30-205 OF HLA-DRA/HLA-DRB1 HETERODIMER IN COMPLEX WITH CD74 PEPTIDE (CLIP), SUBUNIT, GLYCOSYLATION AT ASN-103 AND ASN-143, DISULFIDE BOND.
[32]"X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II."
Dessen A., Lawrence C.M., Cupo S., Zaller D.M., Wiley D.C.
Immunity 7:473-481(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF COMPLEX WITH PEPTIDE FROM COLLAGEN.
[33]"Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein."
Smith K.J., Pyrdol J., Gauthier L., Wiley D.C., Wucherpfennig K.W.
J. Exp. Med. 188:1511-1520(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITH PEPTIDE FROM MYELIN BASIC PROTEIN.
[34]"Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins."
Li Y., Li H., Martin R., Mariuzza R.A.
J. Mol. Biol. 304:177-188(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 26-206 OF HLA-DRA/HLA-DRB5 HETERODIMER IN COMPLEX WITH MBP PEPTIDE, SUBUNIT.
[35]"Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II."
Li Y., Li H., Dimasi N., McCormick J.K., Martin R., Schuck P., Schlievert P.M., Mariuzza R.A.
Immunity 14:93-104(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 26-206 OF HLA-DRA/HLA-DRB5 HETERODIMER IN COMPLEX WITH MBP PEPTIDE AND STREPTOCOCCUS PYOGENES SPEC PEPTIDE, SUBUNIT, DISULFIDE BOND.
[36]"A functional and structural basis for TCR cross-reactivity in multiple sclerosis."
Lang H.L.E., Jacobsen H., Ikemizu S., Andersson C., Harlos K., Madsen L., Hjorth P., Sondergaard L., Svejgaard A., Wucherpfennig K., Stuart D.I., Bell J.I., Jones E.Y., Fugger L.
Nat. Immunol. 3:940-943(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 26-207 OF HLA-DRA/HLA-DRB5 HETERODIMER IN COMPLEX EPSTEIN-BARR VIRUS BALF5 PEPTIDE, SUBUNIT, DISULFIDE BOND.
[37]"Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule."
Li Y., Huang Y., Lue J., Quandt J.A., Martin R., Mariuzza R.A.
EMBO J. 24:2968-2979(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-206 OF HLA-DRA/HLA-DRB5 HETERODIMER IN COMPLEX WITH MBP PEPTIDE AND TRAC, SUBUNIT, DISULFIDE BOND.
[38]"Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity."
Parry C.S., Gorski J., Stern L.J.
J. Mol. Biol. 371:435-446(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 26-207 OF HLA-DRA/HLA-DRB3 HETERODIMER IN COMPLEX WITH ITGB3 PEPTIDE (ALLOANTIGEN HPA-1A), SUBUNIT, DISULFIDE BOND.
[39]"The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles."
Dai S., Crawford F., Marrack P., Kappler J.W.
Proc. Natl. Acad. Sci. U.S.A. 105:11893-11897(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 26-206 OF HLA-DRA/HLA-DRB3 HETERODIMER IN COMPLEX WITH EEF1A2 PEPTIDE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J00194 mRNA. Translation: AAA36275.1.
K01171 mRNA. Translation: AAA59785.1.
X00274 Genomic DNA. Translation: CAA25076.1. Different initiation.
J00204, J00203 Genomic DNA. Translation: AAA36302.1.
M60334 mRNA. Translation: AAA59783.1.
CR457013 mRNA. Translation: CAG33294.1.
AL662796 Genomic DNA. Translation: CAI18266.1.
AL670296 Genomic DNA. Translation: CAI17571.1.
AL935032 Genomic DNA. Translation: CAI18476.1.
BX120007 Genomic DNA. Translation: CAM26203.1.
Z84814 Genomic DNA. Translation: CAB06609.1.
CH471081 Genomic DNA. Translation: EAX03630.1.
BC032350 mRNA. Translation: AAH32350.1.
BC071659 mRNA. Translation: AAH71659.1.
V00523 mRNA. Translation: CAA23782.1.
J00201 Genomic DNA. Translation: AAA36301.1.
AF481359 Genomic DNA. Translation: AAO23887.1.
CCDSCCDS4750.1.
PIRHLHUDA. A93952.
RefSeqNP_061984.2. NM_019111.4.
UniGeneHs.520048.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6AX-ray2.75A30-205[»]
1AQDX-ray2.45A/D/G/J26-217[»]
1BX2X-ray2.60A/D27-206[»]
1D5MX-ray2.00A26-206[»]
1D5XX-ray2.45A26-206[»]
1D5ZX-ray2.00A26-206[»]
1D6EX-ray2.45A26-206[»]
1DLHX-ray2.80A/D28-207[»]
1FV1X-ray1.90A/D26-206[»]
1FYTX-ray2.60A26-206[»]
1H15X-ray3.10A/D26-207[»]
1HQRX-ray3.20A26-206[»]
1HXYX-ray2.60A26-207[»]
1J8HX-ray2.40A26-206[»]
1JWMX-ray2.70A26-207[»]
1JWSX-ray2.60A26-207[»]
1JWUX-ray2.30A26-207[»]
1KG0X-ray2.65A28-207[»]
1KLGX-ray2.40A29-205[»]
1KLUX-ray1.93A29-207[»]
1LO5X-ray3.20A26-207[»]
1PYWX-ray2.10A26-207[»]
1R5IX-ray2.60A/E26-206[»]
1SEBX-ray2.70A/E26-206[»]
1SJEX-ray2.45A28-207[»]
1SJHX-ray2.25A28-207[»]
1T5WX-ray2.40A/D27-206[»]
1T5XX-ray2.50A27-207[»]
1YMMX-ray3.50A26-216[»]
1ZGLX-ray2.80A/D/G/J26-206[»]
2FSEX-ray3.10A/C29-205[»]
2G9HX-ray2.00A26-207[»]
2IAMX-ray2.80A26-207[»]
2IANX-ray2.80A/F/K/P26-207[»]
2ICWX-ray2.41A/D28-206[»]
2IPKX-ray2.30A26-207[»]
2OJEX-ray3.00A/E27-206[»]
2Q6WX-ray2.25A/D26-207[»]
2SEBX-ray2.50A26-206[»]
2WBJX-ray3.00A/E26-218[»]
2XN9X-ray2.30D26-207[»]
3C5JX-ray1.80A26-206[»]
3L6FX-ray2.10A26-207[»]
3O6FX-ray2.80A/E26-207[»]
3PDOX-ray1.95A26-217[»]
3PGCX-ray2.66A/D26-217[»]
3PGDX-ray2.72A/D26-217[»]
3QXAX-ray2.71A/D26-207[»]
3QXDX-ray2.30A/D26-207[»]
3S4SX-ray2.40A/D26-207[»]
3S5LX-ray2.10A/D26-207[»]
3T0EX-ray4.00A26-207[»]
4AENX-ray2.20A26-217[»]
4AH2X-ray2.36A26-217[»]
4E41X-ray2.60A/F26-207[»]
4FQXX-ray2.60A26-216[»]
4GBXX-ray3.00A26-216[»]
4H1LX-ray3.30A/D28-205[»]
4H25X-ray2.20A/D28-207[»]
4H26X-ray2.50A/D28-206[»]
4I5BX-ray2.12A/D27-213[»]
4IS6X-ray2.50A26-207[»]
4MCYX-ray2.30A26-206[»]
4MCZX-ray2.41A26-206[»]
4MD0X-ray2.19A26-206[»]
4MD4X-ray1.95A26-206[»]
4MD5X-ray1.65A26-206[»]
4MDIX-ray2.00A26-206[»]
4MDJX-ray1.70A26-206[»]
ProteinModelPortalP01903.
SMRP01903. Positions 28-206.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109367. 15 interactions.
DIPDIP-6063N.
IntActP01903. 10 interactions.
MINTMINT-203259.
STRING9606.ENSP00000372608.

Protein family/group databases

Allergome8362. Hom s HLA-DR-alpha.

PTM databases

PhosphoSiteP01903.

Polymorphism databases

DMDM122206.

Proteomic databases

MaxQBP01903.
PaxDbP01903.
PRIDEP01903.

Protocols and materials databases

DNASU3122.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000383127; ENSP00000372608; ENSG00000227993.
ENST00000383259; ENSP00000372746; ENSG00000206308.
ENST00000395388; ENSP00000378786; ENSG00000204287.
ENST00000411524; ENSP00000405295; ENSG00000234794.
ENST00000414698; ENSP00000402951; ENSG00000230726.
ENST00000416883; ENSP00000410443; ENSG00000228987.
ENST00000442960; ENSP00000404533; ENSG00000226260.
GeneID3122.
KEGGhsa:3122.
UCSCuc003obh.3. human.

Organism-specific databases

CTD3122.
GeneCardsGC06P032412.
GC06Pj32355.
GC06Pk32382.
GC06Pl32446.
GC06Pm32482.
GC06Pn32365.
GC06Po32413.
H-InvDBHIX0005752.
HIX0031098.
HIX0166957.
HIX0167205.
HIX0167443.
HGNCHGNC:4947. HLA-DRA.
HPACAB002798.
CAB015402.
MIM142860. gene.
610424. phenotype.
neXtProtNX_P01903.
Orphanet505. Graham Little-Piccardi-Lassueur syndrome.
PharmGKBPA35071.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44736.
HOVERGENHBG006862.
InParanoidP01903.
KOK06752.
OMAMIKRSNH.
PhylomeDBP01903.
TreeFamTF333797.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP01903.
BgeeP01903.
CleanExHS_HLA-DRA.
GenevestigatorP01903.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011162. MHC_I/II-like_Ag-recog.
IPR014745. MHC_II_a/b_N.
IPR001003. MHC_II_a_N.
[Graphical view]
PfamPF07654. C1-set. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]
SMARTSM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHLA-DRA. human.
EvolutionaryTraceP01903.
GeneWikiHLA-DRA.
GenomeRNAi3122.
NextBio12390.
PROP01903.
SOURCESearch...

Entry information

Entry nameDRA_HUMAN
AccessionPrimary (citable) accession number: P01903
Secondary accession number(s): A2BET4 expand/collapse secondary AC list , Q30160, Q6IAZ1, Q861I2, Q9TP70
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM