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P04222

- 1C03_HUMAN

UniProt

P04222 - 1C03_HUMAN

Protein

HLA class I histocompatibility antigen, Cw-3 alpha chain

Gene

HLA-C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (22 Aug 2003)
      Previous versions | rss
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    Functioni

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

    GO - Molecular functioni

    1. peptide antigen binding Source: UniProt
    2. TAP binding Source: UniProt

    GO - Biological processi

    1. antigen processing and presentation of exogenous peptide antigen via MHC class I Source: Reactome
    2. antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
    3. antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent Source: Reactome
    4. antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
    5. cytokine-mediated signaling pathway Source: Reactome
    6. innate immune response Source: Reactome
    7. interferon-gamma-mediated signaling pathway Source: Reactome
    8. positive regulation of T cell mediated cytotoxicity Source: InterPro
    9. regulation of immune response Source: Reactome
    10. type I interferon signaling pathway Source: Reactome
    11. viral process Source: UniProtKB-KW

    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-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
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:4933. HLA-C.

    Subcellular locationi

    GO - Cellular componenti

    1. cell surface Source: UniProt
    2. early endosome membrane Source: Reactome
    3. endoplasmic reticulum Source: UniProt
    4. ER to Golgi transport vesicle membrane Source: Reactome
    5. Golgi apparatus Source: UniProt
    6. Golgi membrane Source: Reactome
    7. integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
    8. MHC class I protein complex Source: UniProt
    9. phagocytic vesicle membrane Source: Reactome
    10. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane, MHC I

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Add
    BLAST
    Chaini25 – 366342HLA class I histocompatibility antigen, Cw-3 alpha chainPRO_0000018870Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi110 – 1101N-linked (GlcNAc...)By similarity
    Disulfide bondi125 ↔ 1881 PublicationPROSITE-ProRule annotation
    Disulfide bondi227 ↔ 2831 PublicationPROSITE-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

    MaxQBiP04222.
    PaxDbiP04222.
    PRIDEiP04222.

    Expressioni

    Gene expression databases

    CleanExiHS_HLA-C.
    GenevestigatoriP04222.

    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

    Structurei

    Secondary structure

    1
    366
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi28 – 369
    Turni39 – 413
    Beta strandi45 – 528
    Beta strandi55 – 617
    Beta strandi64 – 663
    Beta strandi69 – 713
    Helixi74 – 774
    Helixi81 – 10828
    Beta strandi118 – 12811
    Beta strandi131 – 15020
    Beta strandi157 – 1615
    Helixi162 – 17312
    Helixi176 – 18510
    Helixi187 – 19812
    Helixi200 – 2034
    Beta strandi210 – 2167
    Beta strandi222 – 23514
    Beta strandi238 – 2436
    Turni249 – 2513
    Beta strandi261 – 2633
    Beta strandi268 – 2747
    Helixi277 – 2804
    Beta strandi281 – 2866
    Beta strandi294 – 2963

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EFXX-ray3.00A25-302[»]
    ProteinModelPortaliP04222.
    SMRiP04222. Positions 25-302.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04222.

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei309 – 33325HelicalSequence AnalysisAdd
    BLAST

    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.
    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.
    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.

    P04222-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRVMAPRTLI LLLSGALALT ETWAGSHSMR YFYTAVSRPG RGEPHFIAVG    50
    YVDDTQFVRF DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQTDRV 100
    SLRNLRGYYN QSEAGSHIIQ RMYGCDVGPD GRLLRGYDQY AYDGKDYIAL 150
    NEDLRSWTAA DTAAQITQRK WEAAREAEQL RAYLEGLCVE WLRRYLKNGK 200
    ETLQRAEHPK THVTHHPVSD HEATLRCWAL GFYPAEITLT WQWDGEDQTQ 250
    DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLTLRWEP 300
    SSQPTIPIVG IVAGLAVLAV LAVLGAVVAV VMCRRKSSGG KGGSCSQAAS 350
    SNSAQGSDES LIACKA 366
    Length:366
    Mass (Da):40,861
    Last modified:August 22, 2003 - v2
    Checksum:i47E55680EA1F6D97
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti33 – 331Y → C in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti64 – 652AA → DE in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti78 – 792QE → RK in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti93 – 931R → P in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti140 – 1401Y → H in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti161 – 1611D → N in CAA25190. (PubMed:6609813)Curated
    Sequence conflicti205 – 2051R → G in CAA25190. (PubMed:6609813)Curated

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti73 – 731A → E.
    Corresponds to variant rs1050409 [ dbSNP | Ensembl ].
    VAR_056461
    Natural varianti76 – 761V → M.
    Corresponds to variant rs1065382 [ dbSNP | Ensembl ].
    VAR_056462
    Natural varianti90 – 901K → N in allele Cw*03:08.
    Corresponds to variant rs28626310 [ dbSNP | Ensembl ].
    VAR_016569
    Natural varianti101 – 1011S → N in allele Cw*03:07.
    VAR_016565
    Natural varianti104 – 1041N → K in allele Cw*03:07.
    VAR_016566
    Natural varianti115 – 1151G → R in allele Cw*03:03 and allele Cw*03:13.
    VAR_016563
    Natural varianti118 – 1181I → T in allele Cw*03:05 and allele Cw*03:13.
    VAR_016564
    Natural varianti119 – 1191I → L in allele Cw*03:02, allele Cw*03:05 and allele Cw*03:13.
    VAR_016567
    Natural varianti121 – 1211R → S in allele Cw*03:05.
    VAR_016617
    Natural varianti127 – 1271V → L in allele Cw*03:09.
    VAR_016618
    Natural varianti138 – 1381D → V in allele Cw*03:06.
    VAR_016619
    Natural varianti140 – 1401Y → S in allele Cw*03:02.
    VAR_016568
    Natural varianti272 – 2721V → M.
    Corresponds to variant rs1050276 [ dbSNP | Ensembl ].
    VAR_056463

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    Hs.77961.

    Genome annotation databases

    EnsembliENST00000457903; ENSP00000390851; ENSG00000225691.
    UCSCiuc011hpe.2. human.

    Polymorphism databases

    DMDMi34223716.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    PIRi A02190. HLHUW3.
    I81231.
    UniGenei Hs.656020.
    Hs.743218.
    Hs.77961.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1EFX X-ray 3.00 A 25-302 [» ]
    ProteinModelPortali P04222.
    SMRi P04222. Positions 25-302.
    ModBasei Search...
    MobiDBi Search...

    Polymorphism databases

    DMDMi 34223716.

    Proteomic databases

    MaxQBi P04222.
    PaxDbi P04222.
    PRIDEi P04222.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000457903 ; ENSP00000390851 ; ENSG00000225691 .
    UCSCi uc011hpe.2. human.

    Organism-specific databases

    GeneCardsi GC06M031236.
    GC06Mm31313.
    HGNCi HGNC:4933. HLA-C.
    MIMi 142840. gene.
    neXtProti NX_P04222.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42056.
    HOVERGENi HBG016709.
    PhylomeDBi P04222.

    Enzyme and pathway databases

    Reactomei REACT_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

    ChiTaRSi HLA-C. human.
    EvolutionaryTracei P04222.
    PROi P04222.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_HLA-C.
    Genevestigatori P04222.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    3.30.500.10. 1 hit.
    InterProi 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.
    IPR027648. MHC_I_a.
    IPR001039. MHC_I_a_a1/a2.
    IPR010579. MHC_I_a_C.
    [Graphical view ]
    Pfami PF07654. C1-set. 1 hit.
    PF00129. MHC_I. 1 hit.
    PF06623. MHC_I_C. 1 hit.
    [Graphical view ]
    PRINTSi PR01638. MHCCLASSI.
    SMARTi SM00407. IGc1. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54452. SSF54452. 1 hit.
    PROSITEi PS50835. IG_LIKE. 1 hit.
    PS00290. IG_MHC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete nucleotide sequence of a gene encoding a functional human class I histocompatibility antigen (HLA-CW3)."
      Sodoyer R., Damotte M., Delovitch T.L., Trucy J., Jordan B.R., Strachan T.
      EMBO J. 3:879-885(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*03:04).
    2. "The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes."
      Zemmour J., Gumperz J.E., Hildebrand W.H., Ward F.E., Marsh S.G.E., Williams R.C., Parham P.
      Tissue Antigens 39:249-257(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CW*03:02).
    3. Domena J.D.
      Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE (ALLELES CW*03:03 AND CW*03:04).
    4. "DNA typing of HLA-C locus alleles in Japanese."
      Wang H., Tokunaga K., Kuwata S.
      Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE (ALLELE CW*03:03).
      Tissue: Peripheral blood.
    5. "Correction of the HLA-Cw3 genomic sequence tentatively identifies it as HLA-Cw*0304."
      Zarling A.L., Smith K.D., Lutz C.T., Lee D.R.
      Immunogenetics 44:82-83(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-206 (ALLELE CW*03:04).
    6. "Sequencing based typing for HLA-C. Identification of three new alleles: Cw*0307, Cw*0502 and Cw*0504."
      Santos S., Vicario J.L., Garcia-Sanchez F., Aviles M.J., Balas A.
      Tissue Antigens 58:34-37(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 26-206 (ALLELE CW*03:07).
    7. "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 (ALLELES CW*03:05; CW*03:06; CW*03:08 AND CW*03:09).
    8. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CW*03:13).
    9. "Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand."
      Boyington J.C., Motyka S.A., Schuck P., Brooks A.G., Sun P.D.
      Nature 405:537-543(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-302 IN COMPLEX WITH KIR2DL2, DISULFIDE BONDS.

    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: October 1, 2014
    This is version 133 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

    External Data

    Dasty 3