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Protein

HLA class I histocompatibility antigen, Cw-4 alpha chain

Gene

HLA-C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the presentation of foreign antigens to the immune system.

GO - Molecular functioni

  • peptide antigen binding Source: UniProtKB
  • receptor binding Source: GO_Central
  • TAP binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Immunity

Enzyme and pathway databases

ReactomeiREACT_111168. Endosomal/Vacuolar pathway.
REACT_111178. ER-Phagosome pathway.
REACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_147694. DAP12 interactions.
REACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
REACT_75795. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class I histocompatibility antigen, Cw-4 alpha chain
Alternative name(s):
MHC class I antigen Cw*4
Gene namesi
Name:HLA-C
Synonyms:HLAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:4933. HLA-C.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 308284ExtracellularSequence AnalysisAdd
BLAST
Transmembranei309 – 33325HelicalSequence AnalysisAdd
BLAST
Topological domaini334 – 36633CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, MHC I

Pathology & Biotechi

Polymorphism and mutation databases

DMDMi231433.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Add
BLAST
Chaini25 – 366342HLA class I histocompatibility antigen, Cw-4 alpha chainPRO_0000018871Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi110 – 1101N-linked (GlcNAc...)By similarity
Disulfide bondi125 ↔ 188PROSITE-ProRule annotation
Disulfide bondi227 ↔ 283PROSITE-ProRule annotation

Post-translational modificationi

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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP30504.
PRIDEiP30504.

Expressioni

Gene expression databases

CleanExiHS_HLA-C.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-40945N.
IntActiP30504. 12 interactions.
MINTiMINT-101019.

Structurei

Secondary structure

1
366
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi27 – 3711Combined sources
Beta strandi45 – 528Combined sources
Beta strandi55 – 6612Combined sources
Beta strandi70 – 734Combined sources
Helixi74 – 774Combined sources
Helixi81 – 10828Combined sources
Beta strandi113 – 1153Combined sources
Beta strandi117 – 12711Combined sources
Beta strandi129 – 14214Combined sources
Beta strandi145 – 1506Combined sources
Beta strandi157 – 1615Combined sources
Helixi162 – 17312Combined sources
Helixi176 – 18510Combined sources
Helixi187 – 19812Combined sources
Helixi200 – 2034Combined sources
Beta strandi210 – 2178Combined sources
Beta strandi219 – 2213Combined sources
Beta strandi223 – 23513Combined sources
Beta strandi238 – 2436Combined sources
Helixi249 – 2513Combined sources
Beta strandi252 – 2543Combined sources
Beta strandi261 – 2633Combined sources
Beta strandi265 – 2739Combined sources
Helixi278 – 2803Combined sources
Beta strandi281 – 2866Combined sources
Beta strandi290 – 2923Combined sources
Beta strandi294 – 2963Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IM9X-ray2.80A/E25-299[»]
1QQDX-ray2.70A26-298[»]
ProteinModelPortaliP30504.
SMRiP30504. Positions 26-298.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30504.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini209 – 29789Ig-like C1-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni25 – 11490Alpha-1Add
BLAST
Regioni115 – 20692Alpha-2Add
BLAST
Regioni207 – 29892Alpha-3Add
BLAST
Regioni299 – 30810Connecting peptide

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42056.
HOVERGENiHBG016709.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProiIPR007110. 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.
IPR027648. MHC_I_a.
IPR001039. MHC_I_a_a1/a2.
IPR010579. MHC_I_a_C.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
PF06623. MHC_I_C. 1 hit.
[Graphical view]
PRINTSiPR01638. MHCCLASSI.
SMARTiSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMiSSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P30504-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVMAPRTLI LLLSGALALT ETWAGSHSMR YFSTSVSWPG RGEPRFIAVG
60 70 80 90 100
YVDDTQFVRF DSDAASPRGE PREPWVEQEG PEYWDRETQK YKRQAQADRV
110 120 130 140 150
NLRKLRGYYN QSEDGSHTLQ RMFGCDLGPD GRLLRGYNQF AYDGKDYIAL
160 170 180 190 200
NEDLRSWTAA DTAAQITQRK WEAAREAEQR RAYLEGTCVE WLRRYLENGK
210 220 230 240 250
ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT WQWDGEDQTQ
260 270 280 290 300
DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWKP
310 320 330 340 350
SSQPTIPIVG IVAGLAVLAV LAVLGAMVAV VMCRRKSSGG KGGSCSQAAS
360
SNSAQGSDES LIACKA
Length:366
Mass (Da):40,995
Last modified:April 1, 1993 - v1
Checksum:iE883EB3968658DCB
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331S → Y in allele Cw*04:03 and allele Cw*04:06.
VAR_016571
Natural varianti35 – 351S → A in allele Cw*04:03 and allele Cw*04:06.
VAR_016572
Natural varianti38 – 381W → R in allele Cw*04:03 and allele Cw*04:06.
VAR_016573
Natural varianti40 – 401G → S in allele Cw*04:03 and allele Cw*04:06.
VAR_016574
Natural varianti45 – 451R → H in allele Cw*04:03 and allele Cw*04:06.
VAR_016575
Natural varianti52 – 521V → L in allele Cw*04:05.
VAR_016576
Natural varianti73 – 731E → A in allele Cw*04:03 and allele Cw*04:06.
VAR_016577
Natural varianti76 – 761V → M.
Corresponds to variant rs1065382 [ dbSNP | Ensembl ].
VAR_056464
Natural varianti90 – 901K → N.
Corresponds to variant rs28626310 [ dbSNP | Ensembl ].
VAR_056465
Natural varianti97 – 971A → T.
Corresponds to variant rs41543814 [ dbSNP | Ensembl ].
VAR_056466
Natural varianti180 – 1801R → L in allele Cw*04:04 and allele Cw*04:06.
VAR_016578
Natural varianti182 – 1821A → V.
Corresponds to variant rs1059539 [ dbSNP | Ensembl ].
VAR_056467
Natural varianti201 – 2011E → K.
Corresponds to variant rs1131103 [ dbSNP | Ensembl ].
VAR_056468
Natural varianti272 – 2721V → M.
Corresponds to variant rs1050276 [ dbSNP | Ensembl ].
VAR_056469
Natural varianti327 – 3271M → V in allele Cw*04:03 and allele Cw*04:06.
VAR_016579

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA59028.
JH0526.
UniGeneiHs.656020.
Hs.743218.
Hs.77961.

Genome annotation databases

EnsembliENST00000400341; ENSP00000383195; ENSG00000206435.
ENST00000400394; ENSP00000383244; ENSG00000206452.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA59028.
JH0526.
UniGeneiHs.656020.
Hs.743218.
Hs.77961.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IM9X-ray2.80A/E25-299[»]
1QQDX-ray2.70A26-298[»]
ProteinModelPortaliP30504.
SMRiP30504. Positions 26-298.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-40945N.
IntActiP30504. 12 interactions.
MINTiMINT-101019.

Polymorphism and mutation databases

DMDMi231433.

Proteomic databases

PaxDbiP30504.
PRIDEiP30504.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000400341; ENSP00000383195; ENSG00000206435.
ENST00000400394; ENSP00000383244; ENSG00000206452.

Organism-specific databases

GeneCardsiGC06M031236.
GC06Mn31226.
GC06Mo31229.
HGNCiHGNC:4933. HLA-C.
MIMi142840. gene.
neXtProtiNX_P30504.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42056.
HOVERGENiHBG016709.

Enzyme and pathway databases

ReactomeiREACT_111168. Endosomal/Vacuolar pathway.
REACT_111178. ER-Phagosome pathway.
REACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_147694. DAP12 interactions.
REACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
REACT_75795. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Miscellaneous databases

ChiTaRSiHLA-C. human.
EvolutionaryTraceiP30504.
SOURCEiSearch...

Gene expression databases

CleanExiHS_HLA-C.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProiIPR007110. 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.
IPR027648. MHC_I_a.
IPR001039. MHC_I_a_a1/a2.
IPR010579. MHC_I_a_C.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
PF06623. MHC_I_C. 1 hit.
[Graphical view]
PRINTSiPR01638. MHCCLASSI.
SMARTiSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMiSSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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. 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.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry namei1C04_HUMAN
AccessioniPrimary (citable) accession number: P30504
Secondary accession number(s): O78067
, O78072, O78090, O78149, Q29921, Q9UM42
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: June 24, 2015
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.