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Protein

HLA class I histocompatibility antigen, Cw-3 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
  • TAP binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-1236977. Endosomal/Vacuolar pathway.
R-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2172127. DAP12 interactions.
R-HSA-877300. Interferon gamma signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class I histocompatibility antigen, Cw-3 alpha chain
Alternative name(s):
MHC class I antigen Cw*3
Gene namesi
Name:HLA-C
Synonyms:HLAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4933. HLA-C.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 308ExtracellularSequence analysisAdd BLAST284
Transmembranei309 – 333HelicalSequence analysisAdd BLAST25
Topological domaini334 – 366CytoplasmicSequence analysisAdd BLAST33

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, MHC I

Pathology & Biotechi

Organism-specific databases

DisGeNETi3107.
MalaCardsiHLA-C.
OpenTargetsiENSG00000225691.
Orphaneti99860. Precursor B-cell acute lymphoblastic leukemia.

Polymorphism and mutation databases

DMDMi34223716.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000001887025 – 366HLA class I histocompatibility antigen, Cw-3 alpha chainAdd BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi110N-linked (GlcNAc...)By similarity1
Disulfide bondi125 ↔ 188PROSITE-ProRule annotation1 Publication
Disulfide bondi227 ↔ 283PROSITE-ProRule annotation1 Publication

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

EPDiP04222.
PeptideAtlasiP04222.
PRIDEiP04222.

PTM databases

SwissPalmiP04222.

Expressioni

Gene expression databases

BgeeiENSG00000225691.
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).By similarity

GO - Molecular functioni

  • TAP binding Source: UniProtKB

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 36Combined sources9
Turni39 – 41Combined sources3
Beta strandi45 – 52Combined sources8
Beta strandi55 – 61Combined sources7
Beta strandi64 – 66Combined sources3
Beta strandi69 – 71Combined sources3
Helixi74 – 77Combined sources4
Helixi81 – 108Combined sources28
Beta strandi118 – 128Combined sources11
Beta strandi131 – 150Combined sources20
Beta strandi157 – 161Combined sources5
Helixi162 – 173Combined sources12
Helixi176 – 185Combined sources10
Helixi187 – 198Combined sources12
Helixi200 – 203Combined sources4
Beta strandi210 – 216Combined sources7
Beta strandi222 – 235Combined sources14
Beta strandi238 – 243Combined sources6
Turni249 – 251Combined sources3
Beta strandi261 – 263Combined sources3
Beta strandi268 – 274Combined sources7
Helixi277 – 280Combined sources4
Beta strandi281 – 286Combined sources6
Beta strandi294 – 296Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFXX-ray3.00A25-302[»]
ProteinModelPortaliP04222.
SMRiP04222.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04222.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 297Ig-like C1-typeAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 114Alpha-1Add BLAST90
Regioni115 – 206Alpha-2Add BLAST92
Regioni207 – 298Alpha-3Add BLAST92
Regioni299 – 308Connecting peptide10

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG016709.
PhylomeDBiP04222.

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.
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]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. 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.

P04222-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVMAPRTLI LLLSGALALT ETWAGSHSMR YFYTAVSRPG RGEPHFIAVG
60 70 80 90 100
YVDDTQFVRF DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQTDRV
110 120 130 140 150
SLRNLRGYYN QSEAGSHIIQ RMYGCDVGPD GRLLRGYDQY AYDGKDYIAL
160 170 180 190 200
NEDLRSWTAA DTAAQITQRK WEAAREAEQL RAYLEGLCVE WLRRYLKNGK
210 220 230 240 250
ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT WQWDGEDQTQ
260 270 280 290 300
DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWEP
310 320 330 340 350
SSQPTIPIVG IVAGLAVLAV LAVLGAVVAV VMCRRKSSGG KGGSCSQAAS
360
SNSAQGSDES LIACKA
Length:366
Mass (Da):40,861
Last modified:August 22, 2003 - v2
Checksum:i47E55680EA1F6D97
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33Y → C in CAA25190 (PubMed:6609813).Curated1
Sequence conflicti64 – 65AA → DE in CAA25190 (PubMed:6609813).Curated2
Sequence conflicti78 – 79QE → RK in CAA25190 (PubMed:6609813).Curated2
Sequence conflicti93R → P in CAA25190 (PubMed:6609813).Curated1
Sequence conflicti140Y → H in CAA25190 (PubMed:6609813).Curated1
Sequence conflicti161D → N in CAA25190 (PubMed:6609813).Curated1
Sequence conflicti205R → G in CAA25190 (PubMed:6609813).Curated1

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05646173A → E.Corresponds to variant rs1050409dbSNPEnsembl.1
Natural variantiVAR_05646276V → M.Corresponds to variant rs1065382dbSNPEnsembl.1
Natural variantiVAR_01656990K → N in allele Cw*03:08. Corresponds to variant rs28626310dbSNPEnsembl.1
Natural variantiVAR_016565101S → N in allele Cw*03:07. Corresponds to variant rs2308557dbSNPEnsembl.1
Natural variantiVAR_016566104N → K in allele Cw*03:07. Corresponds to variant rs17408553dbSNPEnsembl.1
Natural variantiVAR_016563115G → R in allele Cw*03:03 and allele Cw*03:13. Corresponds to variant rs1131122dbSNPEnsembl.1
Natural variantiVAR_016564118I → T in allele Cw*03:05 and allele Cw*03:13. Corresponds to variant rs1131119dbSNPEnsembl.1
Natural variantiVAR_016567119I → L in allele Cw*03:02, allele Cw*03:05 and allele Cw*03:13. Corresponds to variant rs1071649dbSNPEnsembl.1
Natural variantiVAR_016617121R → S in allele Cw*03:05. Corresponds to variant rs41556316dbSNPEnsembl.1
Natural variantiVAR_016618127V → L in allele Cw*03:09. Corresponds to variant rs34592426dbSNPEnsembl.1
Natural variantiVAR_016619138D → V in allele Cw*03:06. Corresponds to variant rs41542424dbSNPEnsembl.1
Natural variantiVAR_016568140Y → S in allele Cw*03:02. Corresponds to variant rs713032dbSNPEnsembl.1
Natural variantiVAR_056463272V → M.Combined sourcesCorresponds to variant rs1050276dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA02190. HLHUW3.
I81231.
UniGeneiHs.656020.
Hs.743218.

Genome annotation databases

EnsembliENST00000457903; ENSP00000390851; ENSG00000225691.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA02190. HLHUW3.
I81231.
UniGeneiHs.656020.
Hs.743218.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFXX-ray3.00A25-302[»]
ProteinModelPortaliP04222.
SMRiP04222.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

SwissPalmiP04222.

Polymorphism and mutation databases

DMDMi34223716.

Proteomic databases

EPDiP04222.
PeptideAtlasiP04222.
PRIDEiP04222.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000457903; ENSP00000390851; ENSG00000225691.

Organism-specific databases

DisGeNETi3107.
GeneCardsiHLA-C.
HGNCiHGNC:4933. HLA-C.
MalaCardsiHLA-C.
MIMi142840. gene.
neXtProtiNX_P04222.
OpenTargetsiENSG00000225691.
Orphaneti99860. Precursor B-cell acute lymphoblastic leukemia.
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG016709.
PhylomeDBiP04222.

Enzyme and pathway databases

ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-1236977. Endosomal/Vacuolar pathway.
R-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2172127. DAP12 interactions.
R-HSA-877300. Interferon gamma signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Miscellaneous databases

ChiTaRSiHLA-C. human.
EvolutionaryTraceiP04222.
PROiP04222.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000225691.
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.
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]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei1C03_HUMAN
AccessioniPrimary (citable) accession number: P04222
Secondary accession number(s): O62883
, O78060, O78068, O78069, P30503, Q29743, Q29992, Q29993, Q9GIK8, Q9TQB4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: August 22, 2003
Last modified: November 2, 2016
This is version 149 of the entry and version 2 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

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 one 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.