MIR2_HHV8P
ID MIR2_HHV8P Reviewed; 256 AA.
AC P90489; D0UZM4; Q2HRC0;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=E3 ubiquitin-protein ligase MIR2;
DE EC=2.3.2.27;
DE AltName: Full=IE1A protein;
DE AltName: Full=Modulator of immune recognition 2;
DE AltName: Full=ORF K5;
DE AltName: Full=RING-type E3 ubiquitin transferase MIR2 {ECO:0000305};
GN Name=K5;
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 [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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE 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 [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=10684303; DOI=10.1128/jvi.74.6.2867-2875.2000;
RA Haque M., Chen J., Ueda K., Mori Y., Nakano K., Hirata Y., Kanamori S.,
RA Uchiyama Y., Inagi R., Okuno T., Yamanishi K.;
RT "Identification and analysis of the K5 gene of Kaposi's sarcoma-associated
RT herpesvirus.";
RL J. Virol. 74:2867-2875(2000).
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, DOMAIN RINGV-TYPE ZINC-FINGER, AND MUTAGENESIS OF CYS-15; CYS-56
RP AND CYS-59.
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 [7]
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 [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 FUNCTION.
RX PubMed=11413168; DOI=10.1172/jci12432;
RA Coscoy L., Ganem D.;
RT "A viral protein that selectively downregulates ICAM-1 and B7-2 and
RT modulates T cell costimulation.";
RL J. Clin. Invest. 107:1599-1606(2001).
RN [10]
RP FUNCTION.
RX PubMed=11751860; DOI=10.1074/jbc.m110265200;
RA Sanchez D.J., Coscoy L., Ganem D.;
RT "Functional organization of MIR2, a novel viral regulator of selective
RT endocytosis.";
RL J. Biol. Chem. 277:6124-6130(2002).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which promotes ubiquitination and
CC subsequent degradation of host MHC-I, CD86, ICAM1 and CD1D molecules,
CC presumably to prevent lysis of infected cells by cytotoxic T-
CC lymphocytes and NK cell. Binds target molecules through transmembrane
CC interaction. E3 ubiquitin-protein ligases accept ubiquitin from
CC specific E2 ubiquitin-conjugating enzymes, and then transfer it to
CC target protein. The result of this ubiquitination is the enhancement of
CC the endocytosis of the target chain and the delivery to the lysosome,
CC where it is proteolytically destroyed. Specific for HLA-A and HLA-B2
CC alleles. {ECO:0000269|PubMed:10799607, ECO:0000269|PubMed:10859362,
CC ECO:0000269|PubMed:11413168, ECO:0000269|PubMed:11751860,
CC ECO:0000269|PubMed:11756476}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds human MHC-I, CD86, ICAM1 and CD1D. {ECO:0000305}.
CC -!- INTERACTION:
CC P90489; P88904: DBP; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7921836;
CC P90489; P88910; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7921977;
CC P90489; P88918; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7922027;
CC P90489; P88941; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7922689;
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:10684303};
CC Multi-pass membrane protein {ECO:0000269|PubMed:10684303}. Host
CC endoplasmic reticulum {ECO:0000269|PubMed:10684303}. Note=Probably
CC exerts its effects at the plasma membrane during viral infection.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U83349; AAC56949.1; -; Genomic_DNA.
DR EMBL; U75698; AAC57094.1; -; Genomic_DNA.
DR EMBL; U71366; AAC34942.1; -; Genomic_DNA.
DR EMBL; AF117253; AAF23881.1; -; mRNA.
DR EMBL; U93872; AAB62655.1; -; Genomic_DNA.
DR EMBL; AF148805; ABD28863.1; -; Genomic_DNA.
DR RefSeq; YP_001129365.1; NC_009333.1.
DR SMR; P90489; -.
DR BioGRID; 1776945; 5.
DR IntAct; P90489; 6.
DR MINT; P90489; -.
DR TCDB; 8.A.159.1.10; the march ubiquitin ligase (march) family.
DR SwissPalm; P90489; -.
DR PRIDE; P90489; -.
DR GeneID; 4961442; -.
DR KEGG; vg:4961442; -.
DR UniPathway; UPA00143; -.
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:0044078; P:positive regulation by symbiont of host receptor-mediated endocytosis; 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; IPR001841; Znf_RING.
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 Early protein; Host cell membrane; Host endoplasmic reticulum;
KW 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..256
FT /note="E3 ubiquitin-protein ligase MIR2"
FT /id="PRO_0000221390"
FT TOPO_DOM 1..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..124
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..256
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 7..66
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 179..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 15
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 18
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 40
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 56
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 59
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT MUTAGEN 15
FT /note="C->S: Loss of B7-2 and ICAM-1 surface expression
FT reduction; when associated with S56 and S-59."
FT /evidence="ECO:0000269|PubMed:10799607"
FT MUTAGEN 56
FT /note="C->S: Loss of ubiquitination; when associated with
FT S-59. Loss of B7-2 and ICAM-1 surface expression reduction;
FT when associated with S-15 and S-59."
FT /evidence="ECO:0000269|PubMed:10799607"
FT MUTAGEN 59
FT /note="C->S: Loss of ubiquitination; when associated with
FT S-56. Loss of B7-2 and ICAM-1 surface expression reduction;
FT when associated with S-15 and S-56."
FT /evidence="ECO:0000269|PubMed:10799607"
SQ SEQUENCE 256 AA; 27939 MW; 9F402B452469E54E CRC64;
MASKDVEEGV EGPICWICRE EVGNEGIHPC ACTGELDVVH PQCLSTWLTV SRNTACQMCR
VIYRTRTQWR SRLNLWPEME RQEIFELFLL MSVVVAGLVG VALCTWTLLV ILTAPAGTFS
PGAVLGFLCF FGFYQIFIVF AFGGICRVSG TVRALYAANN TRVTVLPYRR PRRPTANEDN
IELTVLVGPA GGTDEEPTDE SSEGDVASGD KERDGSSGDE PDGGPNDRAG LRGTARTDLC
APTKKPVRKN HPKNNG
