VIRF2_HHV8P
ID VIRF2_HHV8P Reviewed; 680 AA.
AC Q2HR71; D0UZS4;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 23-FEB-2022, entry version 84.
DE RecName: Full=Viral IRF2-like protein;
DE Short=vIRF-2;
GN Name=vIRF-2;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=10400794; DOI=10.1128/jvi.73.8.6953-6963.1999;
RA Glenn M., Rainbow L., Aurade F., Davison A., Schulz T.F.;
RT "Identification of a spliced gene from Kaposi's sarcoma-associated
RT herpesvirus encoding a protein with similarities to latent membrane
RT proteins 1 and 2A of Epstein-Barr virus.";
RL J. Virol. 73:6953-6963(1999).
RN [2]
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST EI2FAK2.
RX PubMed=11160738; DOI=10.1128/jvi.75.5.2345-2352.2001;
RA Burysek L., Pitha P.M.;
RT "Latently expressed human herpesvirus 8-encoded interferon regulatory
RT factor 2 inhibits double-stranded RNA-activated protein kinase.";
RL J. Virol. 75:2345-2352(2001).
RN [4]
RP FUNCTION.
RX PubMed=21697347; DOI=10.1099/vir.0.034322-0;
RA Mutocheluh M., Hindle L., Areste C., Chanas S.A., Butler L.M., Lowry K.,
RA Shah K., Evans D.J., Blackbourn D.J.;
RT "Kaposi's sarcoma-associated herpesvirus viral interferon regulatory
RT factor-2 inhibits type 1 interferon signalling by targeting interferon-
RT stimulated gene factor-3.";
RL J. Gen. Virol. 92:2394-2398(2011).
RN [5]
RP FUNCTION, MUTAGENESIS OF ARG-82 AND ARG-85, AND DNA-BINDING.
RX PubMed=26537687; DOI=10.1128/jvi.01392-15;
RA Hu H., Dong J., Liang D., Gao Z., Bai L., Sun R., Hu H., Zhang H., Dong Y.,
RA Lan K.;
RT "Genome-Wide Mapping of the Binding Sites and Structural Analysis of
RT Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor
RT 2 Reveal that It Is a DNA-Binding Transcription Factor.";
RL J. Virol. 90:1158-1168(2016).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26797279; DOI=10.1016/j.bbrc.2016.01.087;
RA Kim Y., Cha S., Seo T.;
RT "Activation of the phosphatidylinositol 3-kinase/Akt pathway by viral
RT interferon regulatory factor 2 of Kaposi's sarcoma-associated
RT herpesvirus.";
RL Biochem. Biophys. Res. Commun. 470:650-656(2016).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31059555; DOI=10.1371/journal.ppat.1007743;
RA Koch S., Damas M., Freise A., Hage E., Dhingra A., Rueckert J., Gallo A.,
RA Kremmer E., Tegge W., Broenstrup M., Brune W., Schulz T.F.;
RT "Kaposi's sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-
RT dependent pathway to regulate viral early gene expression.";
RL PLoS Pathog. 15:e1007743-e1007743(2019).
CC -!- FUNCTION: DNA-binding transcription factor that plays a role in the
CC modulation of host immune response (PubMed:26537687, PubMed:31059555).
CC Acts by interacting with host EIF2AK2/PKR and inhibiting its
CC activation. In turn, EIF2AK2/PKR substrates including EIF2S1 or histone
CC H2A are not phosphorylated (PubMed:11160738). Inhibits type I
CC interferon signaling by targeting host IRF3 during viral reactivation
CC from latency (PubMed:11160738, PubMed:21697347). Attenuates the
CC transcriptional activity of host FOXO3 via activation of the AKT1
CC signaling pathway, inhibiting FOXO3-mediated apoptosis
CC (PubMed:26797279). Suppresses also the expression of viral early lytic
CC genes in both newly infected and reactivated infected host cells
CC allowing regulation of viral life cycle by harnessing the interferon
CC pathway. Mechanistically, promotes host PML bodies formation as well as
CC host antiviral restriction factors IFIT1-3 expression leading to
CC inhibition of viral early lytic proteins (PubMed:31059555).
CC {ECO:0000269|PubMed:11160738, ECO:0000269|PubMed:21697347,
CC ECO:0000269|PubMed:26537687, ECO:0000269|PubMed:26797279,
CC ECO:0000269|PubMed:31059555}.
CC -!- SUBUNIT: Interacts with host EIF2AK2/PKR.
CC {ECO:0000269|PubMed:11160738}.
CC -!- INTERACTION:
CC Q2HR71; P19525: EIF2AK2; Xeno; NbExp=2; IntAct=EBI-8876177, EBI-640775;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:11160738,
CC ECO:0000269|PubMed:26797279, ECO:0000269|PubMed:31059555}. Host
CC cytoplasm {ECO:0000269|PubMed:26797279}.
CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC ProRule:PRU00840}.
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DR EMBL; AF148805; ABD28912.1; -; Genomic_DNA.
DR RefSeq; YP_001129414.1; NC_009333.1.
DR PDB; 4P55; X-ray; 2.50 A; A/B=7-114.
DR PDBsum; 4P55; -.
DR SMR; Q2HR71; -.
DR BioGRID; 1776994; 2.
DR IntAct; Q2HR71; 1.
DR PRIDE; Q2HR71; -.
DR DNASU; 4961491; -.
DR GeneID; 4961491; -.
DR KEGG; vg:4961491; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:InterPro.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039580; P:suppression by virus of host PKR signaling; 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:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR CDD; cd00103; IRF; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Host cytoplasm; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host PKR by virus;
KW Inhibition of host RLR pathway by virus;
KW Modulation of host cell apoptosis by virus; Reference proteome;
KW Transcription; Transcription regulation; Viral immunoevasion.
FT CHAIN 1..680
FT /note="Viral IRF2-like protein"
FT /id="PRO_0000423774"
FT DNA_BIND 7..103
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 156..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 343..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..365
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 82
FT /note="R->A: About 50% loss of transcriptional regulation
FT and DNA-binding."
FT /evidence="ECO:0000269|PubMed:26537687"
FT MUTAGEN 85
FT /note="R->A: About 50% loss of transcriptional regulation
FT and DNA-binding."
FT /evidence="ECO:0000269|PubMed:26537687"
FT HELIX 8..20
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4P55"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:4P55"
FT HELIX 54..64
FT /evidence="ECO:0007829|PDB:4P55"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:4P55"
FT STRAND 103..110
FT /evidence="ECO:0007829|PDB:4P55"
SQ SEQUENCE 680 AA; 75090 MW; 0FBC22C8F51F3084 CRC64;
MPRYTESEWL TDFIIDALDS GRFWGVGWLD EQKRIFTVPG RNRRERMPEG FDDFYEAFLE
ERRRHGLPEI PETETGLGCF GRLLRTANRA RQERPFTIYK GKMKLNRWIM TPRPYKGCEG
CLVYLTQEPA MKNMLKALFG IYPHDDKHRE KALRRSLRKK AQREAARKQA AAVATPTTSS
AAEVSSRSQS EDTESSDSEN ELWVGAQGFV GRDMHSLFFE EPEPSGFGSS GQSSSLLAPD
SPRPSTSQVQ GPLHVHTPTD LCLPTGGLPS PVIFPHETQG LLAPPAGQSQ TPFSPEGPVP
SHVSGLDDCL PMVDHIEGCL LDLLSDVGQE LPDLGDLGEL LCETASPQGP MQSEGGEEGS
TESVSVLPAT HPLESSAPGA SVMGSGQELP DLGDLSELLC ETASPQGPMQ SEGGEEGSTE
SVSVLPATHP LESSAPGASV MGSSFQASDN VDDFIDCIPP LCRDDRDVED QEKADQTFYW
YGSDMRPKVL TATQSVAAYL SKKQAIYKVG DKLVPLVVEV YYFGEKVKTH FDLTGGIVIC
SQVPEASPEH ICQTVPPYKC LLPRTAHCSV DANRTLEQTL DRFSMGVVAI GTNMGIFLKG
LLEYPAYFVG NASRRRIGKC RPLSHRHEIQ QAFDVERHNR EPEGSRYASL FLGRRPSPEY
DWDHYPVILH IYLAPFYHRD
