P30504 (1C04_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class I histocompatibility antigen, Cw-4 alpha chain

Alternative name(s):
MHC class I antigen Cw*4

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. Interacts with HTLV-1 p12I accessory protein. Ref.9
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-4 are known: Cw*04:01 Cw*04:03, Cw*04:04, Cw*04:05 and Cw*04:06. The sequence shown is that of Cw*04:01.
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 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-4 alpha chain

PRO_0000018871

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

By similarity

Disulfide bond

227 ↔ 283

By similarity

Natural variations

Natural variant

33

1

S → Y in allele Cw*04:03 and allele Cw*04:06.

VAR_016571

Natural variant

35

1

S → A in allele Cw*04:03 and allele Cw*04:06.

VAR_016572

Natural variant

38

1

W → R in allele Cw*04:03 and allele Cw*04:06.

VAR_016573

Natural variant

40

1

G → S in allele Cw*04:03 and allele Cw*04:06.

VAR_016574

Natural variant

45

1

R → H in allele Cw*04:03 and allele Cw*04:06.

VAR_016575

Natural variant

52

1

V → L in allele Cw*04:05.

VAR_016576

Natural variant

73

1

E → A in allele Cw*04:03 and allele Cw*04:06.

VAR_016577

Natural variant

76

1

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

VAR_056464

Natural variant

90

1

K → N.
Corresponds to variant rs28626310 [ dbSNP | Ensembl ].

VAR_056465

Natural variant

97

1

A → T.
Corresponds to variant rs41543814 [ dbSNP | Ensembl ].

VAR_056466

Natural variant

180

1

R → L in allele Cw*04:04 and allele Cw*04:06.

VAR_016578

Natural variant

182

1

A → V.
Corresponds to variant rs1059539 [ dbSNP | Ensembl ].

VAR_056467

Natural variant

201

1

E → K.
Corresponds to variant rs1131103 [ dbSNP | Ensembl ].

VAR_056468

Natural variant

272

1

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

VAR_056469

Natural variant

327

1

M → V in allele Cw*04:03 and allele Cw*04:06.

VAR_016579

Secondary structure

1

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366

Helix Strand Turn

Details...

Beta strand

27 – 37

11

Beta strand

45 – 52

8

Beta strand

55 – 66

12

Beta strand

70 – 73

4

Helix

74 – 77

4

Helix

81 – 108

28

Beta strand

113 – 115

3

Beta strand

117 – 127

11

Beta strand

129 – 142

14

Beta strand

145 – 150

6

Beta strand

157 – 161

5

Helix

162 – 173

12

Helix

176 – 185

10

Helix

187 – 198

12

Helix

200 – 203

4

Beta strand

210 – 217

8

Beta strand

219 – 221

3

Beta strand

223 – 235

13

Beta strand

238 – 243

6

Helix

249 – 251

3

Beta strand

252 – 254

3

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)
	P30504 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: E883EB3968658DCB	FASTA	366	40,995
	10 20 30 40 50 60 MRVMAPRTLI LLLSGALALT ETWAGSHSMR YFSTSVSWPG RGEPRFIAVG YVDDTQFVRF 70 80 90 100 110 120 DSDAASPRGE PREPWVEQEG PEYWDRETQK YKRQAQADRV NLRKLRGYYN QSEDGSHTLQ 130 140 150 160 170 180 RMFGCDLGPD GRLLRGYNQF AYDGKDYIAL NEDLRSWTAA DTAAQITQRK WEAAREAEQR 190 200 210 220 230 240 RAYLEGTCVE WLRRYLENGK ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT 250 260 270 280 290 300 WQWDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWKP 310 320 330 340 350 360 SSQPTIPIVG IVAGLAVLAV LAVLGAMVAV VMCRRKSSGG KGGSCSQAAS SNSAQGSDES LIACKA

References

[1]	"Unusual HLA-B alleles in two tribes of Brazilian Indians." Belich M.P., Madrigal J.A., Hildebrand W.H., Zemmour J., Williams R.C., Luz R., Petzl-Erler M.L., Parham P. Nature 357:326-329(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*04:01).
[2]	"Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains." Grassi F., Meneveri R., Gullberg M., Lopalco L., Rossi G.B., Lanza P., de Santis C., Brattsand G., Butto S., Ginelli E., Beretta A., Siccardi A.G. J. Exp. Med. 174:53-62(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CW*04:01).
[3]	"Cloning and sequencing full-length HLA-B and -C genes." Cox S.T., McWhinnie A.J., Robinson J., Marsh S.G.E., Parham P., Madrigal J.A., Little A.-M. Tissue Antigens 61:20-48(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*04:01). Tissue: Blood.
[4]	"A sequencing strategy for the rapid sequencing of HLA class I genes using random in vitro DNA transposition." Dunn P.P., van Dam M., Crosby I., Carter V. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 1-365 (ALLELE CW*04:01).
[5]	"HLA-C typing of eleven Papua New Guineans: identification of an HLA-Cw4/Cw2 hybrid allele." Little A.-M., Mason A., Marsh S.G.E., Parham P. Tissue Antigens 48:113-117(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*04:03). Tissue: B-cell.
[6]	"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 OF 26-206 (ALLELES CW*04:04 AND CW*04:05).
[7]	"Identification of a novel HLA-C allele, Cw*0406, in a Singapore Malay." Ren E.C., Haniff F., Loh M.T., Chan S.H., Petersdorf E., Hansen J. Tissue Antigens 53:198-200(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELE CW*04:06).
[8]	"Characterization of a novel HLA-Cw*04 variant in a Laotian family: HLA-Cw*0406." Carbonnelle E., Poirier J.C., Fortier C., Marzais F., Visser C.J.T., Borie C., Toubert A., Raffoux C., Charron D., Tamouza R. Tissue Antigens 53:601-603(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELE CW*04:06).
[9]	"Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12(I) protein." Johnson J.M., Nicot C., Fullen J., Ciminale V., Casareto L., Mulloy J.C., Jacobson S., Franchini G. J. Virol. 75:6086-6094(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTLV-1 ACCESSORY PROTEIN P12I.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84386 mRNA. Translation: AAA59705.1.
X58536 mRNA. Translation: CAA41427.1.
AJ278494 Genomic DNA. Translation: CAB95011.1.
AJ238694 Genomic DNA. Translation: CAB41889.2.
L54059 Genomic DNA. Translation: AAB04639.1.
AH006129 Genomic DNA. Translation: AAC17719.1.
AH006130 Genomic DNA. Translation: AAC17720.1.
AF076476 Genomic DNA. Translation: AAC27626.1.
AH006107 Genomic DNA. Translation: AAC16245.1.

IPI

IPI00795906.

PIR

A59028.
JH0526.

UniGene

Hs.654404.
Hs.656020.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IM9	X-ray	2.80	A/E	25-299	[»]
1QQD	X-ray	2.70	A	26-298	[»]

ProteinModelPortal

P30504.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30504. 12 interactions.

MINT

MINT-101019.

Polymorphism databases

DMDM

231433.

Proteomic databases

PaxDb

P30504.

PRIDE

P30504.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400341; ENSP00000383195; ENSG00000206435.
ENST00000400394; ENSP00000383244; ENSG00000206452.

Organism-specific databases

GeneCards

GC06M031236.
GC06Mn31226.
GC06Mo31229.

HGNC

HGNC:4933. HLA-C.

MIM

142840. gene.

neXtProt

NX_P30504.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42056.

HOVERGEN

HBG016709.

OrthoDB

EOG4F4SBG.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P30504.

CleanEx

HS_HLA-C.

Genevestigator

P30504.

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

P30504.

SOURCE

Search...

Entry information

Entry name

1C04_HUMAN

Accession

Primary (citable) accession number: P30504
Secondary accession number(s): O78067 , O78072, O78090, O78149, Q29921, Q9UM42

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 112 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.