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E3 ubiquitin-protein ligase MIR2 (EC 2 3 2 27) (IE1A protein) (Modulator of immune recognition 2) (ORF K5) (RING-type E3 ubiquitin transferase MIR2)

 MIR2_HHV8P              Reviewed;         256 AA.
P90489; D0UZM4; Q2HRC0;
27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
01-MAY-1997, sequence version 1.
17-JUN-2020, entry version 122.
RecName: Full=E3 ubiquitin-protein ligase MIR2;
EC=2.3.2.27;
AltName: Full=IE1A protein;
AltName: Full=Modulator of immune recognition 2;
AltName: Full=ORF K5;
AltName: Full=RING-type E3 ubiquitin transferase MIR2 {ECO:0000305};
Name=K5;
Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's
sarcoma-associated herpesvirus).
Viruses; Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
NCBI_TaxID=868565;
NCBI_TaxID=9606; Homo sapiens (Human).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=9032328;
Nicholas J., Ruvolo V., Zong J., Ciufo D., Guo H.-G., Reitz M.S.,
Hayward G.S.;
"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.";
J. Virol. 71:1963-1974(1997).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=8962146; DOI=10.1073/pnas.93.25.14862;
Russo J.J., Bohenzky R.A., Chien M.-C., Chen J., Yan M., Maddalena D.,
Parry J.P., Peruzzi D., Edelman I.S., Chang Y., Moore P.S.;
"Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8).";
Proc. Natl. Acad. Sci. U.S.A. 93:14862-14867(1996).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Neipel F., Albrecht J.-C., Ensser A., Huang Y.-Q., Li J.J.,
Friedman-Kien A.E., Fleckenstein B.;
"The genome of human herpesvirus 8 cloned from Kaposi's sarcoma.";
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
PubMed=10684303; DOI=10.1128/jvi.74.6.2867-2875.2000;
Haque M., Chen J., Ueda K., Mori Y., Nakano K., Hirata Y., Kanamori S.,
Uchiyama Y., Inagi R., Okuno T., Yamanishi K.;
"Identification and analysis of the K5 gene of Kaposi's sarcoma-associated
herpesvirus.";
J. Virol. 74:2867-2875(2000).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16760382; DOI=10.1099/vir.0.81919-0;
Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.;
"Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.";
J. Gen. Virol. 87:1781-1804(2006).
[6]
FUNCTION, DOMAIN RINGV-TYPE ZINC-FINGER, AND MUTAGENESIS OF CYS-15; CYS-56
AND CYS-59.
PubMed=10799607; DOI=10.1128/jvi.74.11.5300-5309.2000;
Ishido S., Wang C., Lee B.-S., Cohen G.B., Jung J.U.;
"Downregulation of major histocompatibility complex class I molecules by
Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins.";
J. Virol. 74:5300-5309(2000).
[7]
FUNCTION.
PubMed=10859362; DOI=10.1073/pnas.140129797;
Coscoy L., Ganem D.;
"Kaposi's sarcoma-associated herpesvirus encodes two proteins that block
cell surface display of MHC class I chains by enhancing their
endocytosis.";
Proc. Natl. Acad. Sci. U.S.A. 97:8051-8056(2000).
[8]
FUNCTION.
PubMed=11756476; DOI=10.1083/jcb.200111010;
Coscoy L., Sanchez D.J., Ganem D.;
"A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases
regulates endocytosis of proteins involved in immune recognition.";
J. Cell Biol. 155:1265-1273(2001).
[9]
FUNCTION.
PubMed=11413168; DOI=10.1172/jci12432;
Coscoy L., Ganem D.;
"A viral protein that selectively downregulates ICAM-1 and B7-2 and
modulates T cell costimulation.";
J. Clin. Invest. 107:1599-1606(2001).
[10]
FUNCTION.
PubMed=11751860; DOI=10.1074/jbc.m110265200;
Sanchez D.J., Coscoy L., Ganem D.;
"Functional organization of MIR2, a novel viral regulator of selective
endocytosis.";
J. Biol. Chem. 277:6124-6130(2002).
-!- FUNCTION: E3 ubiquitin-protein ligase which promotes ubiquitination and
subsequent degradation of host MHC-I, CD86, ICAM1 and CD1D molecules,
presumably to prevent lysis of infected cells by cytotoxic T-
lymphocytes and NK cell. 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. Specific for HLA-A and HLA-B2
alleles. {ECO:0000269|PubMed:10799607, ECO:0000269|PubMed:10859362,
ECO:0000269|PubMed:11413168, ECO:0000269|PubMed:11751860,
ECO:0000269|PubMed:11756476}.
-!- CATALYTIC ACTIVITY:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
[acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
EC=2.3.2.27;
-!- PATHWAY: Protein modification; protein ubiquitination.
-!- SUBUNIT: Binds human MHC-I, CD86, ICAM1 and CD1D. {ECO:0000305}.
-!- INTERACTION:
P90489; P88904: DBP; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7921836;
P90489; P88910; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7921977;
P90489; P88918; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7922027;
P90489; P88941; Xeno; NbExp=2; IntAct=EBI-6150009, EBI-7922689;
-!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:10684303};
Multi-pass membrane protein {ECO:0000269|PubMed:10684303}. Host
endoplasmic reticulum {ECO:0000269|PubMed:10684303}. Note=Probably
exerts its effects at the plasma membrane during viral infection.
---------------------------------------------------------------------------
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EMBL; U83349; AAC56949.1; -; Genomic_DNA.
EMBL; U75698; AAC57094.1; -; Genomic_DNA.
EMBL; U71366; AAC34942.1; -; Genomic_DNA.
EMBL; AF117253; AAF23881.1; -; mRNA.
EMBL; U93872; AAB62655.1; -; Genomic_DNA.
EMBL; AF148805; ABD28863.1; -; Genomic_DNA.
RefSeq; YP_001129365.1; NC_009333.1.
SMR; P90489; -.
BioGRID; 1776945; 5.
IntAct; P90489; 6.
MINT; P90489; -.
SwissPalm; P90489; -.
PRIDE; P90489; -.
GeneID; 4961442; -.
KEGG; vg:4961442; -.
KO; K21666; -.
BRENDA; 6.3.2.19; 2803.
UniPathway; UPA00143; -.
Proteomes; UP000000942; Genome.
GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IMP:CACAO.
GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IMP:CACAO.
GO; GO:0044078; P:positive regulation by symbiont of host receptor-mediated endocytosis; IMP:CACAO.
GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
GO; GO:0039504; P:suppression by virus of host adaptive immune response; IMP:CACAO.
GO; GO:0039511; P:suppression by virus of host interferon receptor activity; IEA:UniProtKB-KW.
GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:CACAO.
Gene3D; 3.30.40.10; -; 1.
InterPro; IPR011016; Znf_RING-CH.
InterPro; IPR013083; Znf_RING/FYVE/PHD.
Pfam; PF12906; RINGv; 1.
SMART; SM00744; RINGv; 1.
PROSITE; PS51292; ZF_RING_CH; 1.
1: Evidence at protein level;
Early protein; Host cell membrane; Host endoplasmic reticulum;
Host membrane; 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; Membrane;
Metal-binding; Reference proteome; Transferase; Transmembrane;
Transmembrane helix; Ubl conjugation pathway; Viral immunoevasion; Zinc;
Zinc-finger.
CHAIN 1..256
/note="E3 ubiquitin-protein ligase MIR2"
/id="PRO_0000221390"
TOPO_DOM 1..83
/note="Cytoplasmic"
/evidence="ECO:0000255"
TRANSMEM 84..104
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 105..124
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 125..145
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 146..256
/note="Cytoplasmic"
/evidence="ECO:0000255"
ZN_FING 7..66
/note="RING-CH-type"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
MUTAGEN 15
/note="C->S: Loss of B7-2 and ICAM-1 surface expression
reduction; when associated with S56 and S-59."
/evidence="ECO:0000269|PubMed:10799607"
MUTAGEN 56
/note="C->S: Loss of ubiquitination; when associated with
S-59. Loss of B7-2 and ICAM-1 surface expression reduction;
when associated with S-15 and S-59."
/evidence="ECO:0000269|PubMed:10799607"
MUTAGEN 59
/note="C->S: Loss of ubiquitination; when associated with
S-56. Loss of B7-2 and ICAM-1 surface expression reduction;
when associated with S-15 and S-56."
/evidence="ECO:0000269|PubMed:10799607"
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


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WP1371: G Protein Signaling Pathways
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Related Genes :
[K5] E3 ubiquitin-protein ligase MIR2 (EC 2.3.2.27) (IE1A protein) (Modulator of immune recognition 2) (ORF K5) (RING-type E3 ubiquitin transferase MIR2)
[K3] E3 ubiquitin-protein ligase MIR1 (EC 2.3.2.27) (IE1B protein) (Modulator of immune recognition 1) (ORF K3) (RING-type E3 ubiquitin transferase MIR1)
[TRAF2 TRAP3] TNF receptor-associated factor 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF2) (RING-type E3 ubiquitin transferase TRAF2) (Tumor necrosis factor type 2 receptor-associated protein 3)
[K3] E3 ubiquitin-protein ligase MIR1 (EC 2.3.2.27) (MK3) (Modulator of immune recognition 1 homolog) (ORF K3) (RING-type E3 ubiquitin transferase MIR1)
[Rnf2 DinG Ring1b] E3 ubiquitin-protein ligase RING2 (EC 2.3.2.27) (RING finger protein 1B) (RING1b) (RING finger protein 2) (RING-type E3 ubiquitin transferase RING2)
[Traf2] TNF receptor-associated factor 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF2) (RING-type E3 ubiquitin transferase TRAF2)
[RAG1 RNF74] V(D)J recombination-activating protein 1 (RAG-1) (RING finger protein 74) [Includes: Endonuclease RAG1 (EC 3.1.-.-); E3 ubiquitin-protein ligase RAG1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase RAG1)]
[Uhrf1 Np95] E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (RING-type E3 ubiquitin transferase UHRF1) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (mUhrf1) (Ubiquitin-like-containing PHD and RING finger domains protein 1)
[AMFR RNF45] E3 ubiquitin-protein ligase AMFR (EC 2.3.2.27) (Autocrine motility factor receptor) (AMF receptor) (RING finger protein 45) (RING-type E3 ubiquitin transferase AMFR) (gp78)
[RNF213 ALO17 C17orf27 KIAA1554 KIAA1618 MYSTR] E3 ubiquitin-protein ligase RNF213 (EC 2.3.2.27) (EC 3.6.4.-) (ALK lymphoma oligomerization partner on chromosome 17) (Mysterin) (RING finger protein 213) (RING-type E3 ubiquitin transferase RNF213)
[ubr-1 C32E8.11] E3 ubiquitin-protein ligase ubr-1 (EC 2.3.2.27) (N-recognin-1) (RING-type E3 ubiquitin transferase ubr-1) (Ubiquitin-protein ligase E3-alpha)
[TRAF6 RNF85] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (Interleukin-1 signal transducer) (RING finger protein 85) (RING-type E3 ubiquitin transferase TRAF6)
[RNF2 BAP1 DING HIPI3 RING1B] E3 ubiquitin-protein ligase RING2 (EC 2.3.2.27) (Huntingtin-interacting protein 2-interacting protein 3) (HIP2-interacting protein 3) (Protein DinG) (RING finger protein 1B) (RING1b) (RING finger protein 2) (RING finger protein BAP-1) (RING-type E3 ubiquitin transferase RING2)
[TRAF6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)
[Ubr3 Kiaa2024 Zfp650 Znf650] E3 ubiquitin-protein ligase UBR3 (EC 2.3.2.27) (N-recognin-3) (RING-type E3 ubiquitin transferase UBR3) (Ubiquitin-protein ligase E3-alpha-3) (Ubiquitin-protein ligase E3-alpha-III) (Zinc finger protein 650)
[SH3RF2 POSH3 POSHER PPP1R39 RNF158] E3 ubiquitin-protein ligase SH3RF2 (EC 2.3.2.27) (Heart protein phosphatase 1-binding protein) (HEPP1) (POSH-eliminating RING protein) (Protein phosphatase 1 regulatory subunit 39) (RING finger protein 158) (RING-type E3 ubiquitin transferase SH3RF2) (SH3 domain-containing RING finger protein 2)
[TRIM21 RNF81 RO52 SSA1] E3 ubiquitin-protein ligase TRIM21 (EC 2.3.2.27) (52 kDa Ro protein) (52 kDa ribonucleoprotein autoantigen Ro/SS-A) (RING finger protein 81) (RING-type E3 ubiquitin transferase TRIM21) (Ro(SS-A)) (Sjoegren syndrome type A antigen) (SS-A) (Tripartite motif-containing protein 21)
[DTX3L BBAP] E3 ubiquitin-protein ligase DTX3L (EC 2.3.2.27) (B-lymphoma- and BAL-associated protein) (Protein deltex-3-like) (RING-type E3 ubiquitin transferase DTX3L) (Rhysin-2) (Rhysin2)
[CBLB RNF56 Nbla00127] E3 ubiquitin-protein ligase CBL-B (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene b) (RING finger protein 56) (RING-type E3 ubiquitin transferase CBL-B) (SH3-binding protein CBL-B) (Signal transduction protein CBL-B)
[RNF8 KIAA0646] E3 ubiquitin-protein ligase RNF8 (hRNF8) (EC 2.3.2.27) (RING finger protein 8) (RING-type E3 ubiquitin transferase RNF8)
[RNF43] E3 ubiquitin-protein ligase RNF43 (EC 2.3.2.27) (RING finger protein 43) (RING-type E3 ubiquitin transferase RNF43)
[RAD18 RNF73] E3 ubiquitin-protein ligase RAD18 (EC 2.3.2.27) (Postreplication repair protein RAD18) (hHR18) (hRAD18) (RING finger protein 73) (RING-type E3 ubiquitin transferase RAD18)
[Rnf115 Zfp364 Znf364] E3 ubiquitin-protein ligase RNF115 (EC 2.3.2.27) (RING finger protein 115) (RING-type E3 ubiquitin transferase RNF115) (Rabring 7) (Zinc finger protein 364)
[Traf6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)
[Traf6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)
[Rag1] V(D)J recombination-activating protein 1 (RAG-1) [Includes: Endonuclease RAG1 (EC 3.1.-.-); E3 ubiquitin-protein ligase RAG1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase RAG1)]
[RBX1 RNF75 ROC1] E3 ubiquitin-protein ligase RBX1 (EC 2.3.2.27) (EC 2.3.2.32) (E3 ubiquitin-protein transferase RBX1) (Protein ZYP) (RING finger protein 75) (RING-box protein 1) (Rbx1) (Regulator of cullins 1) (ROC1) [Cleaved into: E3 ubiquitin-protein ligase RBX1, N-terminally processed (E3 ubiquitin-protein transferase RBX1, N-terminally processed)]
[TRAF6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)
[CCNB1IP1 C14orf18 HEI10] E3 ubiquitin-protein ligase CCNB1IP1 (EC 2.3.2.27) (Cyclin-B1-interacting protein 1) (Human enhancer of invasion 10) (RING-type E3 ubiquitin transferase CCNB1IP1)
[TRAF6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)

Bibliography :