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P90495

- MIR1_HHV8P

UniProt

P90495 - MIR1_HHV8P

Protein

E3 ubiquitin-protein ligase MIR1

Gene

K3

Organism
Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    E3 ubiquitin-protein ligase which promotes ubiquitination and subsequent degradation of host MHC-I and CD1D molecules, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes. Binds target molecules through transmembrane interaction. E3 ubiquitin-protein ligases accept ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfer it to target protein. The result of this ubiquitination is the enhancement of the endocytosis of the target chain and the delivery to the lysosome, where it is proteolytically destroyed. Induces ubiquitination not only on lysines, but also on cysteine residues.5 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi12 – 121Zinc
    Metal bindingi24 – 241Zinc
    Metal bindingi26 – 261Zinc
    Metal bindingi34 – 341Zinc
    Metal bindingi37 – 371Zinc
    Metal bindingi50 – 501Zinc
    Metal bindingi53 – 531Zinc

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri1 – 6060RING-CH-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. zinc ion binding Source: InterPro

    GO - Biological processi

    1. endocytosis involved in viral entry into host cell Source: CACAO
    2. modulation by virus of host protein ubiquitination Source: CACAO
    3. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: CACAO
    4. suppression by virus of host adaptive immune response Source: CACAO
    5. suppression by virus of host interferon receptor activity Source: UniProtKB-KW
    6. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon receptors by virus, Inhibition of host interferon signaling pathway by virus, Ubl conjugation pathway, Viral immunoevasion

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase MIR1 (EC:6.3.2.-)
    Alternative name(s):
    IE1B protein
    Modulator of immune recognition 1
    ORF K3
    Gene namesi
    Name:K3
    OrganismiHuman herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus)
    Taxonomic identifieri868565 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000000942: Genome

    Subcellular locationi

    Host cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Host endoplasmic reticulum 1 Publication
    Note: Probably exerts its effects at the plasma membrane during viral infection.

    GO - Cellular componenti

    1. host cell endoplasmic reticulum Source: UniProtKB-SubCell
    2. host cell plasma membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Host cell membrane, Host endoplasmic reticulum, Host membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi41 – 411W → A: Loss of ubiquitination activity and degradation of class I molecules. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 333333E3 ubiquitin-protein ligase MIR1PRO_0000221389Add
    BLAST

    Expressioni

    Keywords - Developmental stagei

    Early protein

    Interactioni

    Subunit structurei

    Binds human MHC-I and CD1D.Curated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    P889412EBI-6149947,EBI-7922689From a different organism.
    P889512EBI-6149947,EBI-7923148From a different organism.

    Protein-protein interaction databases

    IntActiP90495. 16 interactions.
    MINTiMINT-2824800.

    Structurei

    Secondary structure

    1
    333
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni10 – 134
    Helixi29 – 313
    Helixi35 – 4511
    Turni51 – 533

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1VYXNMR-A1-60[»]
    ProteinModelPortaliP90495.
    SMRiP90495. Positions 1-60.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP90495.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8282CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini104 – 12118ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini143 – 333191CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei83 – 10321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei122 – 14221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Contains 1 RING-CH-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri1 – 6060RING-CH-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Transmembrane, Transmembrane helix, Zinc-finger

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    InterProiIPR011016. Znf_RING-CH.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view]
    PfamiPF12906. RINGv. 1 hit.
    [Graphical view]
    SMARTiSM00744. RINGv. 1 hit.
    [Graphical view]
    PROSITEiPS51292. ZF_RING_CH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P90495-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEDEDVPVCW ICNEELGNER FRACGCTGEL ENVHRSCLST WLTISRNTAC    50
    QICGVVYNTR VVWRPLREMT LLPRLTYQEG LELIVFIFIM TLGAAGLAAA 100
    TWVWLYIVGG HDPEIDHVAA AAYYVFFVFY QLFVVFGLGA FFHMMRHVGR 150
    AYAAVNTRVE VFPYRPRPTS PECAVEEIEL QEILPRGDNQ DEEGPAGAAP 200
    GDQNGPAGAA PGDQDGPADG APVHRDSEES VDEAAGYKEA GEPTHNDGRD 250
    DNVEPTAVGC DCNNLGAERY RATYCGGYVG AQSGDGAYSV SCHNKAGPSS 300
    LVDILPQGLP GGGYGSMGVI RKRSAVSSAL MFH 333
    Length:333
    Mass (Da):36,005
    Last modified:May 1, 1997 - v1
    Checksum:iC9CCE79B87D3F553
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti195 – 20410Missing in AAB62674. 1 PublicationCurated
    Sequence conflicti195 – 20410Missing in ABD28858. (PubMed:16760382)Curated
    Sequence conflicti281 – 2811A → V in AAB62674. 1 PublicationCurated
    Sequence conflicti310 – 3101P → L in ABD28858. (PubMed:16760382)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U75698 Genomic DNA. Translation: AAC57091.1.
    AF307516 mRNA. Translation: AAK83788.1.
    AF307517 mRNA. Translation: AAK83789.1.
    AF307518 mRNA. Translation: AAK83790.1.
    AF307519 mRNA. Translation: AAK83791.1.
    U71365 Genomic DNA. Translation: AAC34939.1.
    U83350 Genomic DNA. Translation: AAC56950.1.
    U93872 Genomic DNA. Translation: AAB62674.1.
    AF148805 Genomic DNA. Translation: ABD28858.1.
    RefSeqiYP_001129360.1. NC_009333.1.

    Genome annotation databases

    GeneIDi4961486.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U75698 Genomic DNA. Translation: AAC57091.1 .
    AF307516 mRNA. Translation: AAK83788.1 .
    AF307517 mRNA. Translation: AAK83789.1 .
    AF307518 mRNA. Translation: AAK83790.1 .
    AF307519 mRNA. Translation: AAK83791.1 .
    U71365 Genomic DNA. Translation: AAC34939.1 .
    U83350 Genomic DNA. Translation: AAC56950.1 .
    U93872 Genomic DNA. Translation: AAB62674.1 .
    AF148805 Genomic DNA. Translation: ABD28858.1 .
    RefSeqi YP_001129360.1. NC_009333.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1VYX NMR - A 1-60 [» ]
    ProteinModelPortali P90495.
    SMRi P90495. Positions 1-60.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P90495. 16 interactions.
    MINTi MINT-2824800.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 4961486.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .

    Miscellaneous databases

    EvolutionaryTracei P90495.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR011016. Znf_RING-CH.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view ]
    Pfami PF12906. RINGv. 1 hit.
    [Graphical view ]
    SMARTi SM00744. RINGv. 1 hit.
    [Graphical view ]
    PROSITEi PS51292. ZF_RING_CH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins."
      Nicholas J., Ruvolo V., Zong J., Ciufo D., Guo H.-G., Reitz M.S., Hayward G.S.
      J. Virol. 71:1963-1974(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Transcription pattern of human herpesvirus 8 open reading frame k3 in primary effusion lymphoma and kaposi's sarcoma."
      Rimessi P., Bonaccorsi A., Sturzl M., Fabris M., Brocca-Cofano E., Caputo A., Melucci-Vigo G., Falchi M., Cafaro A., Cassai E., Ensoli B., Monini P.
      J. Virol. 75:7161-7174(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The genome of human herpesvirus 8 cloned from Kaposi's sarcoma."
      Neipel F., Albrecht J.-C., Ensser A., Huang Y.-Q., Li J.J., Friedman-Kien A.E., Fleckenstein B.
      Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview."
      Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.
      J. Gen. Virol. 87:1781-1804(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis."
      Coscoy L., Ganem D.
      Proc. Natl. Acad. Sci. U.S.A. 97:8051-8056(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins."
      Ishido S., Wang C., Lee B.-S., Cohen G.B., Jung J.U.
      J. Virol. 74:5300-5309(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    8. "A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition."
      Coscoy L., Sanchez D.J., Ganem D.
      J. Cell Biol. 155:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation."
      Hewitt E.W., Duncan L., Mufti D., Baker J., Stevenson P.G., Lehner P.J.
      EMBO J. 21:2418-2429(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN HLA-A, DOMAIN RINGV-TYPE ZINC-FINGER, MUTAGENESIS OF TRP-41.
    10. "Regulation of CD1d expression and function by a herpesvirus infection."
      Sanchez D.J., Gumperz J.E., Ganem D.
      J. Clin. Invest. 115:1369-1378(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase."
      Cadwell K., Coscoy L.
      Science 309:127-130(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal domain reveals a Novel E2-binding C4HC3-type RING domain."
      Dodd R.B., Allen M.D., Brown S.E., Sanderson C.M., Duncan L.M., Lehner P.J., Bycroft M., Read R.J.
      J. Biol. Chem. 279:53840-53847(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-60.

    Entry informationi

    Entry nameiMIR1_HHV8P
    AccessioniPrimary (citable) accession number: P90495
    Secondary accession number(s): O40920, Q2HRC5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 27, 2005
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 101 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Specific for HLA-A, HLA-B, HLA-C and HLA-E alleles.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3