P01903 (DRA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	254 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 miroenvironment 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 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. 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 process	Immunity
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome MHC II Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T 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 interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	ER to Golgi transport vesicle membrane Traceable author statement. Source: Reactome Golgi membrane Traceable author statement. Source: Reactome MHC class II protein complex Inferred from electronic annotation. Source: UniProtKB-KW clathrin-coated endocytic vesicle membrane Traceable author statement. Source: Reactome integral to lumenal side of endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to 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 trans-Golgi network membrane Traceable author statement. Source: Reactome
Molecular_function	MHC class II receptor activity Non-traceable author statement Ref.4Ref.13. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.11 Ref.12 Ref.13

Chain

26 – 254

229

HLA class II histocompatibility antigen, DR alpha chain

PRO_0000018947

Regions

Topological domain

26 – 216

191

Extracellular Potential

Transmembrane

217 – 239

23

Helical; Potential

Topological domain

240 – 254

15

Cytoplasmic Potential

Domain

112 – 204

93

Ig-like C1-type

Region

26 – 109

84

Alpha-1

Region

110 – 203

94

Alpha-2

Region

204 – 216

13

Connecting peptide

Amino acid modifications

Glycosylation

103

1

N-linked (GlcNAc...) Ref.26 Ref.31

Glycosylation

143

1

N-linked (GlcNAc...) Ref.26 Ref.31

Disulfide bond

132 ↔ 188

Ref.31 Ref.35 Ref.36 Ref.37 Ref.38

Cross-link

244

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25

Natural variations

Natural variant

16

1

V → L.
Corresponds to variant rs16822586 [ dbSNP | Ensembl ].

VAR_035241

Natural variant

242

1

V → L in allele DRA*01:02.
Corresponds to variant rs7192 [ dbSNP | Ensembl ].

VAR_004399

Experimental info

Mutagenesis

244

1

K → 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 conflict

28 – 29

2

EE → AD AA sequence Ref.13

Sequence conflict

33

1

I → T AA sequence Ref.13

Sequence conflict

34 – 35

2

QA → YP AA sequence Ref.13

Sequence conflict

48

1

M → Q AA sequence Ref.13

Sequence conflict

54

1

D → T AA sequence Ref.13

Sequence conflict

59

1

V → Y AA sequence Ref.12

Sequence conflict

64

1

K → L AA sequence Ref.12

Sequence conflict

67

1

V → A AA sequence Ref.11

Sequence conflict

69

1

R → L AA sequence Ref.12

Sequence conflict

75

1

R → P AA sequence Ref.12

Sequence conflict

78

1

S → D AA sequence Ref.12

Sequence conflict

149

1

N → E AA sequence Ref.11

Secondary structure

1

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254

Helix Strand Turn

Details...

Beta strand

30 – 40

11

Turn

41 – 43

3

Beta strand

44 – 51

8

Beta strand

54 – 60

7

Turn

61 – 64

4

Beta strand

65 – 70

6

Helix

71 – 75

5

Helix

81 – 101

21

Turn

102 – 104

3

Beta strand

113 – 120

8

Beta strand

124 – 126

3

Beta strand

128 – 140

13

Beta strand

143 – 148

6

Beta strand

151 – 153

3

Beta strand

155 – 159

5

Beta strand

170 – 178

9

Beta strand

185 – 191

7

Beta strand

195 – 197

3

Beta strand

199 – 204

6

Sequences

	Sequence		Length	Mass (Da)
	P01903 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 3CD1CDBA952B2350	FASTA	254	28,607
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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.

IPI

IPI00005171.

PIR

HLHUDA. A93952.

RefSeq

NP_061984.2. NM_019111.4.

UniGene

Hs.520048.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A6A	X-ray	2.75	A	30-205	[»]
1AQD	X-ray	2.45	A/D/G/J	26-217	[»]
1BX2	X-ray	2.60	A/D	27-206	[»]
1D5M	X-ray	2.00	A	26-206	[»]
1D5X	X-ray	2.45	A	26-206	[»]
1D5Z	X-ray	2.00	A	26-206	[»]
1D6E	X-ray	2.45	A	26-206	[»]
1DLH	X-ray	2.80	A/D	28-207	[»]
1FV1	X-ray	1.90	A/D	26-206	[»]
1FYT	X-ray	2.60	A	26-206	[»]
1H15	X-ray	3.10	A/D	26-207	[»]
1HQR	X-ray	3.20	A	26-206	[»]
1HXY	X-ray	2.60	A	26-207	[»]
1J8H	X-ray	2.40	A	26-206	[»]
1JWM	X-ray	2.70	A	26-207	[»]
1JWS	X-ray	2.60	A	26-207	[»]
1JWU	X-ray	2.30	A	26-207	[»]
1KG0	X-ray	2.65	A	28-207	[»]
1KLG	X-ray	2.40	A	29-205	[»]
1KLU	X-ray	1.93	A	29-207	[»]
1LO5	X-ray	3.20	A	26-207	[»]
1PYW	X-ray	2.10	A	26-207	[»]
1R5I	X-ray	2.60	A/E	26-206	[»]
1SEB	X-ray	2.70	A/E	26-206	[»]
1SJE	X-ray	2.45	A	28-207	[»]
1SJH	X-ray	2.25	A	28-207	[»]
1T5W	X-ray	2.40	A/D	27-206	[»]
1T5X	X-ray	2.50	A	27-207	[»]
1YMM	X-ray	3.50	A	26-216	[»]
1ZGL	X-ray	2.80	A/D/G/J	26-206	[»]
2FSE	X-ray	3.10	A/C	29-205	[»]
2G9H	X-ray	2.00	A	26-207	[»]
2IAM	X-ray	2.80	A	26-207	[»]
2IAN	X-ray	2.80	A/F/K/P	26-207	[»]
2ICW	X-ray	2.41	A/D	28-206	[»]
2IPK	X-ray	2.30	A	26-207	[»]
2OJE	X-ray	3.00	A/E	27-206	[»]
2Q6W	X-ray	2.25	A/D	26-207	[»]
2SEB	X-ray	2.50	A	26-206	[»]
2WBJ	X-ray	3.00	A/E	26-218	[»]
2XN9	X-ray	2.30	D	26-207	[»]
3C5J	X-ray	1.80	A	26-206	[»]
3L6F	X-ray	2.10	A	26-207	[»]
3O6F	X-ray	2.80	A/E	26-207	[»]
3PDO	X-ray	1.95	A	26-217	[»]
3PGC	X-ray	2.66	A/D	26-217	[»]
3PGD	X-ray	2.72	A/D	26-217	[»]
3QXA	X-ray	2.71	A/D	26-207	[»]
3QXD	X-ray	2.30	A/D	26-207	[»]
3S4S	X-ray	2.40	A/D	26-207	[»]
3S5L	X-ray	2.10	A/D	26-207	[»]
3T0E	X-ray	4.00	A	26-207	[»]
4AEN	X-ray	2.20	A	26-217	[»]
4AH2	X-ray	2.36	A	26-217	[»]
4E41	X-ray	2.60	A/F	26-207	[»]
4FQX	X-ray	2.60	A	26-216	[»]
4GBX	X-ray	3.00	A	26-216	[»]
4H1L	X-ray	3.30	A/D	28-205	[»]

ProteinModelPortal

P01903.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6063N.

IntAct

P01903. 9 interactions.

MINT

MINT-203259.

STRING

9606.ENSP00000372608.

Protein family/group databases

Allergome

8362. Hom s HLA-DR-alpha.

PTM databases

PhosphoSite

P01903.

Polymorphism databases

DMDM

122206.

Proteomic databases

PaxDb

P01903.

PRIDE

P01903.

Protocols and materials databases

DNASU

3122.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000383127; ENSP00000372608; ENSG00000227993.
ENST00000383259; ENSP00000372746; ENSG00000206308.
ENST00000395388; ENSP00000378786; ENSG00000204287.
ENST00000411524; ENSP00000405295; ENSG00000234794.
ENST00000414698; ENSP00000402951; ENSG00000230726.
ENST00000416883; ENSP00000410443; ENSG00000228987.
ENST00000442960; ENSP00000404533; ENSG00000226260.

GeneID

3122.

KEGG

hsa:3122.

UCSC

uc003obh.3. human.

Organism-specific databases

CTD

3122.

GeneCards

GC06P032412.

H-InvDB

HIX0005752.
HIX0031098.
HIX0166957.
HIX0167205.
HIX0167443.

HGNC

HGNC:4947. HLA-DRA.

HPA

CAB002798.
CAB015402.

MIM

142860. gene.
610424. phenotype.

neXtProt

NX_P01903.

Orphanet

505. Graham Little-Piccardi-Lassueur syndrome.

PharmGKB

PA35071.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44736.

HOVERGEN

HBG006862.

InParanoid

P01903.

KO

K06752.

OrthoDB

EOG4N5VZ0.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01903.

Bgee

P01903.

CleanEx

HS_HLA-DRA.

Genevestigator

P01903.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.
3.10.320.10. 1 hit.

InterPro

IPR007110. 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]

Pfam

PF07654. C1-set. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]

SMART

SM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]

SUPFAM

SSF54452. MHC_I/II-like_Ag-recog. 1 hit.

PROSITE

PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HLA-DRA. human.

EvolutionaryTrace

P01903.

GenomeRNAi

3122.

NextBio

12390.

SOURCE

Search...

Entry information

Entry name

DRA_HUMAN

Accession

Primary (citable) accession number: P01903
Secondary accession number(s): A2BET4 , Q30160, Q6IAZ1, Q861I2, Q9TP70

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.