Q29963 (1C06_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class I histocompatibility antigen, Cw-6 alpha chain

Alternative name(s):
MHC class I antigen Cw*6

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 transcript 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-6 are known: Cw*06:02 Cw*06:03 and Cw*06:04. Allele Cw*062 is a risk factor that confers susceptibility to psoriasis. The sequence shown is that of Cw*06:02.
Involvement in disease	Psoriasis 1 (PSORS1) [MIM:177900]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8
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	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-6 alpha chain		PRO_0000018873
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	D → Y in allele Cw*06:03.		VAR_016620
	Natural variant	43	1	E → K. Corresponds to variant rs1050438 [ dbSNP | Ensembl ].		VAR_056474
	Natural variant	48	1	S → A. Corresponds to variant rs707911 [ dbSNP | Ensembl ].		VAR_061447
	Natural variant	48	1	S → P. Corresponds to variant rs707911 [ dbSNP | Ensembl ].		VAR_061448
	Natural variant	48	1	S → T. Corresponds to variant rs707911 [ dbSNP | Ensembl ].		VAR_061449
	Natural variant	73	1	A → E. Corresponds to variant rs1050409 [ dbSNP | Ensembl ].		VAR_056475
	Natural variant	76	1	V → M. Corresponds to variant rs1065382 [ dbSNP | Ensembl ].		VAR_056476
	Natural variant	90	1	K → N. Corresponds to variant rs28626310 [ dbSNP | Ensembl ].		VAR_056477
	Natural variant	97	1	A → T. Corresponds to variant rs41543814 [ dbSNP | Ensembl ].		VAR_056478
	Natural variant	137	1	Y → H. Corresponds to variant rs2308574 [ dbSNP | Ensembl ].		VAR_056479
	Natural variant	180	1	W → L in allele Cw*06:04.		VAR_016621
	Natural variant	182	1	A → V. Corresponds to variant rs1059539 [ dbSNP | Ensembl ].		VAR_056480
	Natural variant	201	1	E → K. Corresponds to variant rs1131103 [ dbSNP | Ensembl ].		VAR_056481
	Natural variant	272	1	V → M. Corresponds to variant rs1050276 [ dbSNP | Ensembl ].		VAR_056482
Experimental info
	Sequence conflict	33	1	D → C in AAA57258. Ref.3
	Sequence conflict	202	1	T → S in AAA36235. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q29963 [UniParc]. Last modified August 22, 2003. Version 2. Checksum: 45876CB22256DE80	FASTA	366	40,969
	10 20 30 40 50 60 MRVMAPRTLI LLLSGALALT ETWACSHSMR YFDTAVSRPG RGEPRFISVG YVDDTQFVRF 70 80 90 100 110 120 DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQADRV NLRKLRGYYN QSEDGSHTLQ 130 140 150 160 170 180 WMYGCDLGPD GRLLRGYDQS AYDGKDYIAL NEDLRSWTAA DTAAQITQRK WEAAREAEQW 190 200 210 220 230 240 RAYLEGTCVE WLRRYLENGK ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT 250 260 270 280 290 300 WQRDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWEP 310 320 330 340 350 360 SSQPTIPIVG IVAGLAVLAV LAVLGAVMAV VMCRRKSSGG KGGSCSQAAS SNSAQGSDES LIACKA

References

[1]	"Isolation and expression of a cDNA clone encoding HLA-CW6: unique characteristics of HLA-C encoded gene products." Mizuno S., Kang S.H., Lee H.W., Trapani J.A., Dupont B., Yang S.Y. Immunogenetics 29:323-330(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CW*06:02).
[2]	"Isolation and characterization of a genomic HLA-Cw6 clone." Steinle A., Noessner E., Schendel D.J. Tissue Antigens 39:134-137(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*06:02).
[3]	"Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles." Pohla H., Kuon W., Tabaczewski P., Doerner C., Weiss E.H. Immunogenetics 29:297-307(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-366 (ALLELE CW*06:02).
[4]	"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 (ALLELE CW*06:03).
[5]	"Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701." Inoue T., Ogawa A., Tokunaga K., Ishikawa Y., Kashiwase K., Tanaka H., Park M.H., Jia G.J., Chimge N.-O., Sideltseva E.W., Akaza T., Tadokoro K., Takahashi T., Juji T. Tissue Antigens 53:534-544(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELE CW*06:04). Tissue: Blood.
[6]	"HLA-C and guttate psoriasis." Mallon E., Bunce M., Savoie H., Rowe A., Newson R., Gotch F., Bunker C.B. Br. J. Dermatol. 143:1177-1182(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF ALLELE CW*06:02 WITH PSORIASIS.
[7]	"Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR." Helms C., Saccone N.L., Cao L., Daw J.A.W., Cao K., Hsu T.M., Taillon-Miller P., Duan S., Gordon D., Pierce B., Ott J., Rice J., Fernandez-Vina M.A., Kwok P.-Y., Menter A., Bowcock A.M. Hum. Genet. 118:466-476(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF ALLELE CW*06:02 WITH PSORIASIS.
[8]	"Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene." Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V.C., Jenisch S., Weichenthal M., Abecasis G.R., Lim H.W., Christophers E., Voorhees J.J., Elder J.T. Am. J. Hum. Genet. 78:827-851(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PSORS1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M28160 mRNA. Translation: AAA36235.1. Z22752, Z22753, Z22754 Genomic DNA. Translation: CAA80437.1. M28206 mRNA. Translation: AAA57258.1. AF019568, AF019567 Genomic DNA. Translation: AAC17721.1. AB008136 Genomic DNA. Translation: BAA22919.1.
IPI	IPI00744964.
PIR	I68749.
UniGene	Hs.654404. Hs.656020.
3D structure databases
ProteinModelPortal	Q29963.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q29963. 1 interaction.
Polymorphism databases
DMDM	34305706.
Proteomic databases
PRIDE	Q29963.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000420206; ENSP00000410214; ENSG00000228299.
UCSC	uc011gas.2. human.
Organism-specific databases
GeneCards	GC06M031236. GC06Mk31228.
HGNC	HGNC:4933. HLA-C.
MIM	142840. gene. 177900. phenotype.
neXtProt	NX_Q29963.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG016709.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q29963.
CleanEx	HS_HLA-C.
Genevestigator	Q29963.
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.
SOURCE	Search...

Entry information

Entry name

1C06_HUMAN

Accession

Primary (citable) accession number: Q29963
Secondary accession number(s): O19505, O78063, Q29989

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 22, 2003
Last sequence update:	August 22, 2003
Last modified:	May 1, 2013
This is version 111 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.