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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: -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

Keywordsi

Biological processImmunity

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
SIGNORiP04222

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
MIMi142840 gene
neXtProtiNX_P04222

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Membrane, MHC I

Pathology & Biotechi

Organism-specific databases

DisGeNETi3107
MalaCardsiHLA-C
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...) asparagineBy 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

iPTMnetiP04222
SwissPalmiP04222

Expressioni

Gene expression databases

CleanExiHS_HLA-C

Interactioni

Subunit structurei

Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
KIR2DL3P436283EBI-13917186,EBI-8632435

GO - Molecular functioni

  • TAP binding Source: UniProtKB

Protein-protein interaction databases

IntActiP04222, 8 interactors

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

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
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011161 MHC_I-like_Ag-recog
IPR037055 MHC_I-like_Ag-recog_sf
IPR011162 MHC_I/II-like_Ag-recog
IPR001039 MHC_I_a_a1/a2
IPR010579 MHC_I_a_C
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00129 MHC_I, 1 hit
PF06623 MHC_I_C, 1 hit
PRINTSiPR01638 MHCCLASSI
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit

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 dbSNP:rs1050409Ensembl.1
Natural variantiVAR_05646276V → M. Corresponds to variant dbSNP:rs1065382Ensembl.1
Natural variantiVAR_01656990K → N in allele Cw*03:08. Corresponds to variant dbSNP:rs28626310Ensembl.1
Natural variantiVAR_016565101S → N in allele Cw*03:07. Corresponds to variant dbSNP:rs2308557Ensembl.1
Natural variantiVAR_016566104N → K in allele Cw*03:07. Corresponds to variant dbSNP:rs17408553Ensembl.1
Natural variantiVAR_016563115G → R in allele Cw*03:03 and allele Cw*03:13. Corresponds to variant dbSNP:rs1131122Ensembl.1
Natural variantiVAR_016564118I → T in allele Cw*03:05 and allele Cw*03:13. Corresponds to variant dbSNP:rs1131119Ensembl.1
Natural variantiVAR_016567119I → L in allele Cw*03:02, allele Cw*03:05 and allele Cw*03:13. Corresponds to variant dbSNP:rs1071649Ensembl.1
Natural variantiVAR_016617121R → S in allele Cw*03:05. Corresponds to variant dbSNP:rs41556316Ensembl.1
Natural variantiVAR_016618127V → L in allele Cw*03:09. Corresponds to variant dbSNP:rs34592426Ensembl.1
Natural variantiVAR_016619138D → V in allele Cw*03:06. Corresponds to variant dbSNP:rs41542424Ensembl.1
Natural variantiVAR_016568140Y → S in allele Cw*03:02. Corresponds to variant dbSNP:rs713032Ensembl.1
Natural variantiVAR_056463272V → MCombined sourcesCorresponds to variant dbSNP:rs1050276Ensembl.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

Similar proteinsi

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 historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: August 22, 2003
Last modified: July 18, 2018
This is version 158 of the entry and version 2 of the sequence. See 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

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