MIR1_HHV8P
ID MIR1_HHV8P Reviewed; 333 AA.
AC P90495; O40920; Q2HRC5;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=E3 ubiquitin-protein ligase MIR1;
DE EC=2.3.2.36 {ECO:0000269|PubMed:15994556};
DE AltName: Full=IE1B protein;
DE AltName: Full=Modulator of immune recognition 1;
DE AltName: Full=ORF K3;
DE AltName: Full=RING-type E3 ubiquitin transferase MIR1 {ECO:0000305};
GN Name=K3;
OS Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's
OS sarcoma-associated herpesvirus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=868565;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9032328; DOI=10.1128/jvi.71.3.1963-1974.1997;
RA Nicholas J., Ruvolo V., Zong J., Ciufo D., Guo H.-G., Reitz M.S.,
RA Hayward G.S.;
RT "A single 13-kilobase divergent locus in the Kaposi sarcoma-associated
RT herpesvirus (human herpesvirus 8) genome contains nine open reading frames
RT that are homologous to or related to cellular proteins.";
RL J. Virol. 71:1963-1974(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11435597; DOI=10.1128/jvi.75.15.7161-7174.2001;
RA Rimessi P., Bonaccorsi A., Sturzl M., Fabris M., Brocca-Cofano E.,
RA Caputo A., Melucci-Vigo G., Falchi M., Cafaro A., Cassai E., Ensoli B.,
RA Monini P.;
RT "Transcription pattern of human herpesvirus 8 open reading frame k3 in
RT primary effusion lymphoma and kaposi's sarcoma.";
RL J. Virol. 75:7161-7174(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Neipel F., Albrecht J.-C., Ensser A., Huang Y.-Q., Li J.J.,
RA Friedman-Kien A.E., Fleckenstein B.;
RT "The genome of human herpesvirus 8 cloned from Kaposi's sarcoma.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8962146; DOI=10.1073/pnas.93.25.14862;
RA Russo J.J., Bohenzky R.A., Chien M.-C., Chen J., Yan M., Maddalena D.,
RA Parry J.P., Peruzzi D., Edelman I.S., Chang Y., Moore P.S.;
RT "Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8).";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14862-14867(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16760382; DOI=10.1099/vir.0.81919-0;
RA Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.;
RT "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.";
RL J. Gen. Virol. 87:1781-1804(2006).
RN [6]
RP FUNCTION.
RX PubMed=10859362; DOI=10.1073/pnas.140129797;
RA Coscoy L., Ganem D.;
RT "Kaposi's sarcoma-associated herpesvirus encodes two proteins that block
RT cell surface display of MHC class I chains by enhancing their
RT endocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8051-8056(2000).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10799607; DOI=10.1128/jvi.74.11.5300-5309.2000;
RA Ishido S., Wang C., Lee B.-S., Cohen G.B., Jung J.U.;
RT "Downregulation of major histocompatibility complex class I molecules by
RT Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins.";
RL J. Virol. 74:5300-5309(2000).
RN [8]
RP FUNCTION.
RX PubMed=11756476; DOI=10.1083/jcb.200111010;
RA Coscoy L., Sanchez D.J., Ganem D.;
RT "A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases
RT regulates endocytosis of proteins involved in immune recognition.";
RL J. Cell Biol. 155:1265-1273(2001).
RN [9]
RP INTERACTION WITH HUMAN HLA-A, DOMAIN RINGV-TYPE ZINC-FINGER, AND
RP MUTAGENESIS OF TRP-41.
RX PubMed=12006494; DOI=10.1093/emboj/21.10.2418;
RA Hewitt E.W., Duncan L., Mufti D., Baker J., Stevenson P.G., Lehner P.J.;
RT "Ubiquitylation of MHC class I by the K3 viral protein signals
RT internalization and TSG101-dependent degradation.";
RL EMBO J. 21:2418-2429(2002).
RN [10]
RP FUNCTION.
RX PubMed=15864354; DOI=10.1172/jci200524041;
RA Sanchez D.J., Gumperz J.E., Ganem D.;
RT "Regulation of CD1d expression and function by a herpesvirus infection.";
RL J. Clin. Invest. 115:1369-1378(2005).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15994556; DOI=10.1126/science.1110340;
RA Cadwell K., Coscoy L.;
RT "Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase.";
RL Science 309:127-130(2005).
RN [12]
RP STRUCTURE BY NMR OF 1-60.
RX PubMed=15465811; DOI=10.1074/jbc.m409662200;
RA Dodd R.B., Allen M.D., Brown S.E., Sanderson C.M., Duncan L.M.,
RA Lehner P.J., Bycroft M., Read R.J.;
RT "Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-
RT terminal domain reveals a Novel E2-binding C4HC3-type RING domain.";
RL J. Biol. Chem. 279:53840-53847(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which promotes ubiquitination and
CC subsequent degradation of host MHC-I and CD1D molecules, presumably to
CC prevent lysis of infected cells by cytotoxic T-lymphocytes. Binds
CC target molecules through transmembrane interaction. E3 ubiquitin-
CC protein ligases accept ubiquitin from specific E2 ubiquitin-conjugating
CC enzymes, and then transfer it to target protein. The result of this
CC ubiquitination is the enhancement of the endocytosis of the target
CC chain and the delivery to the lysosome, where it is proteolytically
CC destroyed. Induces ubiquitination not only on lysines, but also on
CC cysteine residues. {ECO:0000269|PubMed:10799607,
CC ECO:0000269|PubMed:10859362, ECO:0000269|PubMed:11756476,
CC ECO:0000269|PubMed:15864354, ECO:0000269|PubMed:15994556}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.; EC=2.3.2.36;
CC Evidence={ECO:0000269|PubMed:15994556};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds human MHC-I and CD1D. {ECO:0000305}.
CC -!- INTERACTION:
CC P90495; P88951: RIR2; Xeno; NbExp=2; IntAct=EBI-6149947, EBI-7923148;
CC P90495; P88941; Xeno; NbExp=2; IntAct=EBI-6149947, EBI-7922689;
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:10799607};
CC Multi-pass membrane protein {ECO:0000269|PubMed:10799607}. Host
CC endoplasmic reticulum {ECO:0000269|PubMed:10799607}. Note=Probably
CC exerts its effects at the plasma membrane during viral infection.
CC -!- MISCELLANEOUS: Specific for HLA-A, HLA-B, HLA-C and HLA-E alleles.
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DR EMBL; U75698; AAC57091.1; -; Genomic_DNA.
DR EMBL; AF307516; AAK83788.1; -; mRNA.
DR EMBL; AF307517; AAK83789.1; -; mRNA.
DR EMBL; AF307518; AAK83790.1; -; mRNA.
DR EMBL; AF307519; AAK83791.1; -; mRNA.
DR EMBL; U71365; AAC34939.1; -; Genomic_DNA.
DR EMBL; U83350; AAC56950.1; -; Genomic_DNA.
DR EMBL; U93872; AAB62674.1; -; Genomic_DNA.
DR EMBL; AF148805; ABD28858.1; -; Genomic_DNA.
DR RefSeq; YP_001129360.1; NC_009333.1.
DR PDB; 1VYX; NMR; -; A=1-60.
DR PDBsum; 1VYX; -.
DR SMR; P90495; -.
DR BioGRID; 1776989; 15.
DR IntAct; P90495; 16.
DR MINT; P90495; -.
DR PRIDE; P90495; -.
DR DNASU; 4961486; -.
DR GeneID; 4961486; -.
DR KEGG; vg:4961486; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P90495; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IMP:CACAO.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IMP:CACAO.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0039504; P:suppression by virus of host adaptive immune response; IMP:CACAO.
DR GO; GO:0039511; P:suppression by virus of host interferon receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:CACAO.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Early protein; Host cell membrane;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon receptors by virus;
KW Inhibition of host interferon signaling pathway by virus; Membrane;
KW Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..333
FT /note="E3 ubiquitin-protein ligase MIR1"
FT /id="PRO_0000221389"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..121
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 1..60
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 187..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 9
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 12
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 34
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT MUTAGEN 41
FT /note="W->A: Loss of ubiquitination activity and
FT degradation of class I molecules."
FT /evidence="ECO:0000269|PubMed:12006494"
FT CONFLICT 195..204
FT /note="Missing (in Ref. 3; AAB62674 and 5; ABD28858)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="A -> V (in Ref. 3; AAB62674)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="P -> L (in Ref. 5; ABD28858)"
FT /evidence="ECO:0000305"
FT TURN 10..13
FT /evidence="ECO:0007829|PDB:1VYX"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:1VYX"
FT HELIX 35..45
FT /evidence="ECO:0007829|PDB:1VYX"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:1VYX"
SQ SEQUENCE 333 AA; 36005 MW; C9CCE79B87D3F553 CRC64;
MEDEDVPVCW ICNEELGNER FRACGCTGEL ENVHRSCLST WLTISRNTAC QICGVVYNTR
VVWRPLREMT LLPRLTYQEG LELIVFIFIM TLGAAGLAAA TWVWLYIVGG HDPEIDHVAA
AAYYVFFVFY QLFVVFGLGA FFHMMRHVGR AYAAVNTRVE VFPYRPRPTS PECAVEEIEL
QEILPRGDNQ DEEGPAGAAP GDQNGPAGAA PGDQDGPADG APVHRDSEES VDEAAGYKEA
GEPTHNDGRD DNVEPTAVGC DCNNLGAERY RATYCGGYVG AQSGDGAYSV SCHNKAGPSS
LVDILPQGLP GGGYGSMGVI RKRSAVSSAL MFH
