P04222 (1C03_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	HLA-C
Synonyms:	HLAC

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	366 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	Heterodimer of an 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 Cw-3 are known: Cw*03:02 (Cw3.2), Cw*03:03, Cw*03:04 (Cw3.1), Cw*03:05, Cw*03:06, Cw*03:07, Cw*03:08, Cw*03:09 and Cw*03:13. The sequence shown is that of Cw*03:04.
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 phagocytic vesicle membrane Traceable author statement. Source: Reactome plasma 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 – 366

342

HLA class I histocompatibility antigen, Cw-3 alpha chain

PRO_0000018870

Regions

Topological domain

25 – 308

284

Extracellular Potential

Transmembrane

309 – 333

25

Helical; Potential

Topological domain

334 – 366

33

Cytoplasmic Potential

Domain

209 – 297

89

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.9

Disulfide bond

227 ↔ 283

Ref.9

Natural variations

Natural variant

73

1

A → E.
Corresponds to variant rs1050409 [ dbSNP | Ensembl ].

VAR_056461

Natural variant

76

1

V → M.
Corresponds to variant rs1065382 [ dbSNP | Ensembl ].

VAR_056462

Natural variant

90

1

K → N in allele Cw*03:08.
Corresponds to variant rs28626310 [ dbSNP | Ensembl ].

VAR_016569

Natural variant

101

1

S → N in allele Cw*03:07.

VAR_016565

Natural variant

104

1

N → K in allele Cw*03:07.

VAR_016566

Natural variant

115

1

G → R in allele Cw*03:03 and allele Cw*03:13.

VAR_016563

Natural variant

118

1

I → T in allele Cw*03:05 and allele Cw*03:13.

VAR_016564

Natural variant

119

1

I → L in allele Cw*03:02, allele Cw*03:05 and allele Cw*03:13.

VAR_016567

Natural variant

121

1

R → S in allele Cw*03:05.

VAR_016617

Natural variant

127

1

V → L in allele Cw*03:09.

VAR_016618

Natural variant

138

1

D → V in allele Cw*03:06.

VAR_016619

Natural variant

140

1

Y → S in allele Cw*03:02.

VAR_016568

Natural variant

272

1

V → M.
Corresponds to variant rs1050276 [ dbSNP | Ensembl ].

VAR_056463

Experimental info

Sequence conflict

33

1

Y → C in CAA25190. Ref.1

Sequence conflict

64 – 65

2

AA → DE in CAA25190. Ref.1

Sequence conflict

78 – 79

2

QE → RK in CAA25190. Ref.1

Sequence conflict

93

1

R → P in CAA25190. Ref.1

Sequence conflict

140

1

Y → H in CAA25190. Ref.1

Sequence conflict

161

1

D → N in CAA25190. Ref.1

Sequence conflict

205

1

R → G in CAA25190. Ref.1

Secondary structure

1

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366

Helix Strand Turn

Details...

Beta strand

28 – 36

9

Turn

39 – 41

3

Beta strand

45 – 52

8

Beta strand

55 – 61

7

Beta strand

64 – 66

3

Beta strand

69 – 71

3

Helix

74 – 77

4

Helix

81 – 108

28

Beta strand

118 – 128

11

Beta strand

131 – 150

20

Beta strand

157 – 161

5

Helix

162 – 173

12

Helix

176 – 185

10

Helix

187 – 198

12

Helix

200 – 203

4

Beta strand

210 – 216

7

Beta strand

222 – 235

14

Beta strand

238 – 243

6

Turn

249 – 251

3

Beta strand

261 – 263

3

Beta strand

268 – 274

7

Helix

277 – 280

4

Beta strand

281 – 286

6

Beta strand

294 – 296

3

Sequences

	Sequence		Length	Mass (Da)
	P04222 [UniParc]. Last modified August 22, 2003. Version 2. Checksum: 47E55680EA1F6D97	FASTA	366	40,861
	10 20 30 40 50 60 MRVMAPRTLI LLLSGALALT ETWAGSHSMR YFYTAVSRPG RGEPHFIAVG YVDDTQFVRF 70 80 90 100 110 120 DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQTDRV SLRNLRGYYN QSEAGSHIIQ 130 140 150 160 170 180 RMYGCDVGPD GRLLRGYDQY AYDGKDYIAL NEDLRSWTAA DTAAQITQRK WEAAREAEQL 190 200 210 220 230 240 RAYLEGLCVE WLRRYLKNGK ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT 250 260 270 280 290 300 WQWDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWEP 310 320 330 340 350 360 SSQPTIPIVG IVAGLAVLAV LAVLGAVVAV VMCRRKSSGG KGGSCSQAAS SNSAQGSDES LIACKA

References

[1]	"Complete nucleotide sequence of a gene encoding a functional human class I histocompatibility antigen (HLA-CW3)." Sodoyer R., Damotte M., Delovitch T.L., Trucy J., Jordan B.R., Strachan T. EMBO J. 3:879-885(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*03:04).
[2]	"The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes." Zemmour J., Gumperz J.E., Hildebrand W.H., Ward F.E., Marsh S.G.E., Williams R.C., Parham P. Tissue Antigens 39:249-257(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CW*03:02).
[3]	Domena J.D. Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ALLELES CW*03:03 AND CW*03:04).
[4]	"DNA typing of HLA-C locus alleles in Japanese." Wang H., Tokunaga K., Kuwata S. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*03:03). Tissue: Peripheral blood.
[5]	"Correction of the HLA-Cw3 genomic sequence tentatively identifies it as HLA-Cw*0304." Zarling A.L., Smith K.D., Lutz C.T., Lee D.R. Immunogenetics 44:82-83(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-206 (ALLELE CW*03:04).
[6]	"Sequencing based typing for HLA-C. Identification of three new alleles: Cw*0307, Cw*0502 and Cw*0504." Santos S., Vicario J.L., Garcia-Sanchez F., Aviles M.J., Balas A. Tissue Antigens 58:34-37(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 26-206 (ALLELE CW*03:07).
[7]	"Sequence-based typing provides a new look at HLA-C diversity." Turner S., Ellexson M.E., Hickman H.D., Sidebottom D.A., Fernandez-Vina M., Confer D.L., Hildebrand W.H. J. Immunol. 161:1406-1413(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELES CW*03:05; CW*03:06; CW*03:08 AND CW*03:09).
[8]	"Sequence of two new HLA-Cw alleles: HLA-Cw*0313 and HLA-Cw*1208." Cox S.T., Ogilvie H., Bohan E.M., Holman R., Prentice H.G., Potter M., Madrigal J.A., Little A.-M. Tissue Antigens 59:49-51(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CW*03:13).
[9]	"Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand." Boyington J.C., Motyka S.A., Schuck P., Brooks A.G., Sun P.D. Nature 405:537-543(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-302 IN COMPLEX WITH KIR2DL2, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00495 Genomic DNA. Translation: CAA25190.1.
M84172 mRNA. Translation: AAA59686.1.
M99389 mRNA. Translation: AAA88088.1.
M99390 mRNA. Translation: AAA88089.1.
D50853 mRNA. Translation: BAA32610.1.
U44064 Genomic DNA. Translation: AAB02773.1.
AF039198 Genomic DNA. Translation: AAD37816.1.
AH006125 Genomic DNA. Translation: AAC17715.1.
AH006126 Genomic DNA. Translation: AAC17716.1.
AH006127 Genomic DNA. Translation: AAC17717.1.
AH006128 Genomic DNA. Translation: AAC17718.1.
AJ298116 Genomic DNA. Translation: CAC18746.1.

IPI

IPI00651697.

PIR

HLHUW3. A02190.
I81231.

UniGene

Hs.654404.
Hs.656020.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EFX	X-ray	3.00	A	25-302	[»]

ProteinModelPortal

P04222.

ModBase

Search...

Polymorphism databases

DMDM

34223716.

Proteomic databases

PaxDb

P04222.

PRIDE

P04222.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000457903; ENSP00000390851; ENSG00000225691.

UCSC

uc011hpe.2. human.

Organism-specific databases

GeneCards

GC06M031236.

HGNC

HGNC:4933. HLA-C.

MIM

142840. gene.

neXtProt

NX_P04222.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42056.

HOVERGEN

HBG016709.

OrthoDB

EOG4F4SBG.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04222.

CleanEx

HS_HLA-C.

Genevestigator

P04222.

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

ChiTaRS

HLA-C. human.

EvolutionaryTrace

P04222.

SOURCE

Search...

Entry information

Entry name

1C03_HUMAN

Accession

Primary (citable) accession number: P04222
Secondary accession number(s): O62883 , O78060, O78068, O78069, P30503, Q29743, Q29992, Q29993, Q9GIK8, Q9TQB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	August 22, 2003
Last modified:	May 1, 2013
This is version 119 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.