P04439 (1A03_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class I histocompatibility antigen, A-3 alpha chain

Alternative name(s):
MHC class I antigen A*3

Gene names

Name:	HLA-A
Synonyms:	HLAA

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	365 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	Involved in the presentation of foreign antigens to the immune system.
Subunit structure	Dimer of alpha chain and a beta chain (beta-2-microglobulin). Interacts with human herpesvirus 8 MIR1 protein By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Polyubiquitinated in a post ER compartment by interaction with human herpesvirus 8 MIR1 protein. This targets the protein for rapid degradation via the ubiquitin system By similarity.
Polymorphism	The following alleles of A-3 are known: A*03:01 (A-3.1), A*03:02, A*03:04, A*03:05 and A*03:06. The sequence shown is that of A*03:01.
Sequence similarities	Belongs to the MHC class I family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Host-virus interaction Immunity
Cellular component	MHC I Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent Traceable author statement. Source: Reactome interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome regulation of immune response Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	ER to Golgi transport vesicle membrane Traceable author statement. Source: Reactome Golgi membrane Traceable author statement. Source: Reactome MHC class I protein complex Inferred from electronic annotation. Source: UniProtKB-KW early endosome 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.1. Source: UniProtKB phagocytic vesicle membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 365

341

HLA class I histocompatibility antigen, A-3 alpha chain

PRO_0000018815

Regions

Topological domain

25 – 308

284

Extracellular Potential

Transmembrane

309 – 332

24

Helical; Potential

Topological domain

333 – 365

33

Cytoplasmic Potential

Domain

209 – 295

87

Ig-like C1-type

Region

25 – 114

90

Alpha-1

Region

115 – 206

92

Alpha-2

Region

207 – 298

92

Alpha-3

Region

299 – 308

10

Connecting peptide

Amino acid modifications

Glycosylation

110

1

N-linked (GlcNAc...) By similarity

Disulfide bond

125 ↔ 188

Ref.13

Disulfide bond

227 ↔ 283

Ref.13

Natural variations

Natural variant

89

1

R → G.
Corresponds to variant rs1059459 [ dbSNP | Ensembl ].

VAR_050310

Natural variant

94

1

Q → H.
Corresponds to variant rs1059463 [ dbSNP | Ensembl ].

VAR_050311

Natural variant

101

1

D → N.
Corresponds to variant rs1136688 [ dbSNP | Ensembl ].

VAR_050312

Natural variant

121

1

I → M.
Corresponds to variant rs1136695 [ dbSNP | Ensembl ].

VAR_050313

Natural variant

129

1

S → P.
Corresponds to variant rs1136700 [ dbSNP | Ensembl ].

VAR_050314

Natural variant

131

1

G → W.
Corresponds to variant rs1136702 [ dbSNP | Ensembl ].

VAR_050315

Natural variant

133

1

F → L.
Corresponds to variant rs1059488 [ dbSNP | Ensembl ].

VAR_050316

Natural variant

151

1

N → K.
Corresponds to variant rs1059509 [ dbSNP | Ensembl ].

VAR_050317

Natural variant

166

1

I → T.
Corresponds to variant rs1059516 [ dbSNP | Ensembl ].

VAR_050318

Natural variant

169

1

R → H.
Corresponds to variant rs1059520 [ dbSNP | Ensembl ].

VAR_050319

Natural variant

176

1

E → V in allele A*03:02.

VAR_004351

Natural variant

180

1

L → Q in allele A*03:02.

VAR_004352

Natural variant

185

1

D → E in allele A*03:05.
Corresponds to variant rs1059542 [ dbSNP | Ensembl ].

VAR_016604

Natural variant

186

1

G → A in allele A*03:06.

VAR_033149

Natural variant

199

1

G → R in allele A*03:04.

VAR_016605

Natural variant

205

1

R → H.
Corresponds to variant rs17185861 [ dbSNP | Ensembl ].

VAR_050320

Experimental info

Sequence conflict

319

1

G → A in AAB66582. Ref.8

Secondary structure

1

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365

Helix Strand Turn

Details...

Beta strand

27 – 36

10

Turn

39 – 41

3

Beta strand

45 – 52

8

Beta strand

55 – 61

7

Beta strand

64 – 66

3

Turn

74 – 78

5

Helix

81 – 109

29

Beta strand

113 – 115

3

Beta strand

118 – 127

10

Beta strand

133 – 150

18

Beta strand

157 – 161

5

Helix

162 – 173

12

Helix

176 – 185

10

Helix

187 – 198

12

Turn

199 – 202

4

Beta strand

210 – 221

12

Beta strand

223 – 235

13

Beta strand

238 – 246

9

Beta strand

251 – 254

4

Beta strand

261 – 263

3

Beta strand

265 – 273

9

Helix

278 – 280

3

Beta strand

281 – 286

6

Beta strand

290 – 292

3

Beta strand

294 – 296

3

Sequences

	Sequence		Length	Mass (Da)
	P04439 [UniParc]. Last modified August 22, 2003. Version 2. Checksum: DEDFCEC4450E0580	FASTA	365	40,841
	10 20 30 40 50 60 MAVMAPRTLL LLLSGALALT QTWAGSHSMR YFFTSVSRPG RGEPRFIAVG YVDDTQFVRF 70 80 90 100 110 120 DSDAASQRME PRAPWIEQEG PEYWDQETRN VKAQSQTDRV DLGTLRGYYN QSEAGSHTIQ 130 140 150 160 170 180 IMYGCDVGSD GRFLRGYRQD AYDGKDYIAL NEDLRSWTAA DMAAQITKRK WEAAHEAEQL 190 200 210 220 230 240 RAYLDGTCVE WLRRYLENGK ETLQRTDPPK THMTHHPISD HEATLRCWAL GFYPAEITLT 250 260 270 280 290 300 WQRDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PKPLTLRWEL 310 320 330 340 350 360 SSQPTIPIVG IIAGLVLLGA VITGAVVAAV MWRRKSSDRK GGSYTQAASS DSAQGSDVSL TACKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide sequence of a functional class I HLA gene, HLA-A3: implications for the evolution of HLA genes." Strachan T., Sodoyer R., Damotte M., Jordan B.R. EMBO J. 3:887-894(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE A*03:01).
[2]	Ellexson M.E., Hildebrand W.H. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ALLELE A*03:01).
[3]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE A*03:01).
[4]	"Molecular cloning and DNA sequence analysis of genes encoding cytotoxic T lymphocyte-defined HLA-A3 subtypes: the E1 subtype." Cowan E.P., Jordan B.E., Coligan J.E. J. Immunol. 135:2835-2841(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE A*03:02).
[5]	"Complete coding sequence of HLA-A*0302." Bettinotti M.P., Hadzikadic L., Adams S., Marincola F.M. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ALLELE A*03:02).
[6]	"Full length sequence of an HLA-A*0301 intron 2 variant." Mayor N.P. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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].
[8]	"Complete cDNA coding sequence of a new HLA-A3 subtype (A*0304) with a new HLA polymorphism at exon 3." Santos S., Balas A., Garcia-Sanchez F., Lillo R., Merino J.L., Vicario J.L. Immunogenetics 49:360-361(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-341 (ALLELE A*03:04).
[9]	"Novel human HLA-A alleles identified in potential bone marrow donors." Becher M.P., Wu J., Williams T. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 26-206 (ALLELE A*03:05).
[10]	"Identification of a HLA-A*03 new variant." Poli F., Frison S., Crespiatico L., Longhi E. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 26-298 (ALLELE A*03:05). Tissue: Blood.
[11]	"Novel HLA-A locus alleles including A*01012, A*0306, A*0308, A*2616, A*2617, A*3009, A*3206, A*3403, A*3602 and A*6604." Bradshaw D., Gans C.P., Jones P., Rizzuto G., Steiner N., Mitton W., Ng J., Koester R., Hartzman R.J., Hurley C.K. Tissue Antigens 59:325-327(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELE A*03:06).
[12]	"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].
[13]	"Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis." McMahon R.M., Friis L., Siebold C., Friese M.A., Fugger L., Jones E.Y. Acta Crystallogr. D 67:447-454(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-298 (ALLELE A*03:01) IN COMPLEX WITH PLP1 ANTIGENIC PEPTIDE, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00492 Genomic DNA. Translation: CAA25162.1. Sequence problems.
U32184 mRNA. Translation: AAB63980.1.
BA000025 Genomic DNA. Translation: BAB63400.1.
AF217561 mRNA. Translation: AAF28734.1.
AF015930 mRNA. Translation: AAB66582.1.
AH008295 Genomic DNA. Translation: AAF03243.1.
AJ401085 Genomic DNA. Translation: CAC06086.1.
AJ401086 Genomic DNA. Translation: CAC06087.1.
AJ401087 Genomic DNA. Translation: CAC06088.1.
AJ748743 Genomic DNA. Translation: CAG38621.1.
AL671277 Genomic DNA. Translation: CAI18372.1.
AH009116 Genomic DNA. Translation: AAF29557.1.

IPI

IPI00647634.

PIR

HLHUA3. A02192.

RefSeq

NP_002107.3. NM_002116.7.

UniGene

Hs.181244.
Hs.713441.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XPG	X-ray	2.60	A	25-298	[»]
3RL2	X-ray	2.39	A	25-298	[»]

ProteinModelPortal

P04439.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04439. 3 interactions.

Polymorphism databases

DMDM

34223717.

Proteomic databases

PaxDb

P04439.

PRIDE

P04439.

Protocols and materials databases

DNASU

3105.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000376809; ENSP00000366005; ENSG00000206503.
ENST00000396634; ENSP00000379873; ENSG00000206503.

GeneID

3105.

KEGG

hsa:3105.

UCSC

uc003nok.3. human.

Organism-specific databases

CTD

3105.

GeneCards

GC06P029933.

HGNC

HGNC:4931. HLA-A.

MIM

142800. gene.

neXtProt

NX_P04439.

PharmGKB

PA35055.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42056.

HOVERGEN

HBG016709.

KO

K06751.

OrthoDB

EOG4F4SBG.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_2pathway. IL12-mediated signaling events.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04439.

Bgee

P04439.

CleanEx

HS_HLA-A.

Genevestigator

P04439.

GermOnline

ENSG00000204632. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.
3.30.500.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011161. MHC_I-like_Ag-recog.
IPR011162. MHC_I/II-like_Ag-recog.
IPR001039. MHC_I_a_a1/a2.
IPR010579. MHC_I_a_C.
[Graphical view]

Pfam

PF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
PF06623. MHC_I_C. 1 hit.
[Graphical view]

PRINTS

PR01638. MHCCLASSI.

SMART

SM00407. IGc1. 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

ChEMBL

CHEMBL2632.

ChiTaRS

HLA-A. human.

GenomeRNAi

3105.

NextBio

12319.

PMAP-CutDB

P04439.

SOURCE

Search...

Entry information

Entry name

1A03_HUMAN

Accession

Primary (citable) accession number: P04439
Secondary accession number(s): O19546 , O19756, Q65A82, Q9GJE6, Q9GJE7, Q9GJE8, Q9MYE6, Q9MYG4, Q9TPR8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 22, 2003
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 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.