ORF45_HHV8P
ID ORF45_HHV8P Reviewed; 407 AA.
AC F5HDE4;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Protein ORF45;
GN Name=ORF45;
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 INTERACTION WITH HOST IRF7, PHOSPHORYLATION AT SER-41 AND SER-162, AND
RP FUNCTION.
RX PubMed=11943871; DOI=10.1073/pnas.082420599;
RA Zhu F.X., King S.M., Smith E.J., Levy D.E., Yuan Y.;
RT "A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated
RT induction of type I interferon by blocking IRF-7 phosphorylation and
RT nuclear accumulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:5573-5578(2002).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=12634379; DOI=10.1128/jvi.77.7.4221-4230.2003;
RA Zhu F.X., Yuan Y.;
RT "The ORF45 protein of Kaposi's sarcoma-associated herpesvirus is associated
RT with purified virions.";
RL J. Virol. 77:4221-4230(2003).
RN [5]
RP EARLY PROTEIN.
RX PubMed=15353285; DOI=10.2741/1394;
RA Lacoste V., de la Fuente C., Kashanchi F., Pumfery A.;
RT "Kaposi's sarcoma-associated herpesvirus immediate early gene activity.";
RL Front. Biosci. 9:2245-2272(2004).
RN [6]
RP NUCLEAR EXPORT SIGNAL, AND SUBCELLULAR LOCATION.
RX PubMed=19116250; DOI=10.1128/jvi.02209-08;
RA Li X., Zhu F.;
RT "Identification of the nuclear export and adjacent nuclear localization
RT signals for ORF45 of Kaposi's sarcoma-associated herpesvirus.";
RL J. Virol. 83:2531-2539(2009).
RN [7]
RP FUNCTION.
RX PubMed=20485504; DOI=10.1371/journal.pone.0010573;
RA Zhu F.X., Sathish N., Yuan Y.;
RT "Antagonism of host antiviral responses by Kaposi's sarcoma-associated
RT herpesvirus tegument protein ORF45.";
RL PLoS ONE 5:E10573-E10573(2010).
RN [8]
RP FUNCTION, PHOSPHORYLATION AT SER-41 AND SER-162, AND MUTAGENESIS OF SER-41
RP AND SER-162.
RX PubMed=22787218; DOI=10.1128/jvi.05224-11;
RA Liang Q., Fu B., Wu F., Li X., Yuan Y., Zhu F.;
RT "ORF45 of Kaposi's sarcoma-associated herpesvirus inhibits phosphorylation
RT of interferon regulatory factor 7 by IKKepsilon and TBK1 as an alternative
RT substrate.";
RL J. Virol. 86:10162-10172(2012).
RN [9]
RP FUNCTION, MUTAGENESIS OF PHE-66, AND INTERACTION WITH HOST RPS6KA1.
RX PubMed=30842327; DOI=10.1128/jvi.02154-18;
RA Li X., Huang L., Xiao Y., Yao X., Long X., Zhu F., Kuang E.;
RT "Development of an ORF45-Derived Peptide To Inhibit the Sustained RSK
RT Activation and Lytic Replication of Kaposi's Sarcoma-Associated
RT Herpesvirus.";
RL J. Virol. 93:0-0(2019).
RN [10]
RP INTERACTION WITH HOST RAB11FIP5, AND SUBCELLULAR LOCATION.
RX PubMed=33315947; DOI=10.1371/journal.ppat.1009099;
RA Wei X., Dong J., Cheng C.C., Ji M., Yu L., Luo S., Wu S., Bai L., Lan K.;
RT "Host RAB11FIP5 protein inhibits the release of Kaposi's sarcoma-associated
RT herpesvirus particles by promoting lysosomal degradation of ORF45.";
RL PLoS Pathog. 16:e1009099-e1009099(2020).
RN [11]
RP FUNCTION, INTERACTION WITH HOST TP53, AND MUTAGENESIS OF GLU-223 AND
RP SER-226.
RX PubMed=34523970; DOI=10.1128/jvi.01459-21;
RA Alzhanova D., Meyo J.O., Juarez A., Dittmer D.P.;
RT "The ORF45 protein of Kaposi Sarcoma-associated Herpesvirus (KSHV) is an
RT inhibitor of p53 signaling during viral reactivation.";
RL J. Virol. 0:0-0(2021).
CC -!- FUNCTION: Prevents the establishment of cellular antiviral state by
CC blocking virus-induced phosphorylation and activation of host
CC interferon regulatory factor 7/IRF7, a transcription factor critical
CC for the induction of interferons alpha and beta. Mechanistically, ORF45
CC competes with the associated IRF7 and inhibits its phosphorylation by
CC IKBKE or TBK1 by acting as an alternative substrate (PubMed:11943871,
CC PubMed:22787218). Also plays a role in promoting the late transcription
CC and translation of viral lytic genes by constitutively activating host
CC extracellular signal-regulated kinase (ERK)-p90 ribosomal S6
CC kinase/RPS6KA1 (PubMed:30842327). In addition, supports the viral
CC replication cycle by modulating host TP53 signaling pathway. Interacts
CC with host TP53 and prevents its interaction with the deubiquitinase
CC USP7, leading to sequestration of TP53 in the host cytoplasm thereby
CC diminishing its transcriptional activity (PubMed:34523970).
CC {ECO:0000269|PubMed:11943871, ECO:0000269|PubMed:20485504,
CC ECO:0000269|PubMed:30842327, ECO:0000269|PubMed:34523970}.
CC -!- SUBUNIT: Interacts with host IRF7 (PubMed:11943871). Interacts with
CC host RPS6KA1 (PubMed:30842327). Interacts with host RAB11FIP5; this
CC interaction results in the lysosomal degradation of ORF45 and the
CC inhibition of viral particle release (PubMed:33315947). Interacts with
CC host TP53; this interaction down-regulates TP53 signaling pathway
CC (PubMed:34523970). {ECO:0000269|PubMed:11943871,
CC ECO:0000269|PubMed:30842327, ECO:0000269|PubMed:33315947,
CC ECO:0000269|PubMed:34523970}.
CC -!- INTERACTION:
CC F5HDE4; Q92985: IRF7; Xeno; NbExp=3; IntAct=EBI-8843990, EBI-968267;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000269|PubMed:12634379}.
CC Host cytoplasm {ECO:0000269|PubMed:19116250}. Host nucleus
CC {ECO:0000269|PubMed:19116250}. Host Golgi apparatus
CC {ECO:0000269|PubMed:33315947}.
CC -!- PTM: Phosphorylated on Ser-41 and Ser-162 by host IKBKE and TBK1.
CC {ECO:0000269|PubMed:11943871, ECO:0000269|PubMed:22787218}.
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DR EMBL; AF148805; ABD28895.1; -; Genomic_DNA.
DR RefSeq; YP_001129397.1; NC_009333.1.
DR PDB; 7OPM; X-ray; 2.45 A; C=27-40.
DR PDB; 7OPO; X-ray; 2.75 A; B/D/F/H/J/L=16-76.
DR PDBsum; 7OPM; -.
DR PDBsum; 7OPO; -.
DR SMR; F5HDE4; -.
DR BioGRID; 1776977; 18.
DR IntAct; F5HDE4; 1.
DR iPTMnet; F5HDE4; -.
DR PRIDE; F5HDE4; -.
DR DNASU; 4961474; -.
DR GeneID; 4961474; -.
DR KEGG; vg:4961474; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IDA:CACAO.
DR GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Early protein; Host cytoplasm; Host Golgi apparatus;
KW Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host IRF7 by virus; Inhibition of host RLR pathway by virus;
KW Phosphoprotein; Reference proteome; Viral immunoevasion; Virion;
KW Virion tegument.
FT CHAIN 1..407
FT /note="Protein ORF45"
FT /id="PRO_0000423770"
FT REGION 1..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 284..294
FT /note="Nuclear export signal"
FT MOTIF 297..300
FT /note="Nuclear localization signal"
FT COMPBIAS 29..43
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..117
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..258
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="Phosphoserine; by host TBK1 and IKKE"
FT /evidence="ECO:0000269|PubMed:11943871,
FT ECO:0000269|PubMed:22787218"
FT MOD_RES 162
FT /note="Phosphoserine; by host TBK1 and IKKE"
FT /evidence="ECO:0000269|PubMed:11943871,
FT ECO:0000269|PubMed:22787218"
FT MUTAGEN 41
FT /note="S->A: Impairs the inhibition of host IRF7
FT transactivation activity."
FT /evidence="ECO:0000269|PubMed:22787218"
FT MUTAGEN 66
FT /note="F->A: Loss of sustained host ERK-RSK activation and
FT decreases lytic replication."
FT /evidence="ECO:0000269|PubMed:30842327"
FT MUTAGEN 162
FT /note="S->A: Impairs the inhibition of host IRF7
FT transactivation activity."
FT /evidence="ECO:0000269|PubMed:22787218"
FT MUTAGEN 223
FT /note="E->A: Loss of TP53 sequestration to the host
FT cytoplasm; when associated with A-226."
FT /evidence="ECO:0000269|PubMed:34523970"
FT MUTAGEN 226
FT /note="S->A: Loss of TP53 sequestration to the host
FT cytoplasm; when associated with A-223."
FT /evidence="ECO:0000269|PubMed:34523970"
SQ SEQUENCE 407 AA; 43327 MW; F8F5876EFDA2BB35 CRC64;
MAMFVRTSSS THDEERMLPI EGAPRRRPPV KFIFPPPPLS SLPGFGRPRG YAGPTVIDMS
APDDVFAEDT PSPPATPLDL QISPDQSSGE SEYDEDEEDE DEEENDDVQE EDEPEGYPAD
FFQPLSHLRP RPLARRAHTP KPVAVVAGRV RSSTDTAESE ASMGWVSQDD GFSPAGLSPS
DDEGVAILEP MAAYTGTGAY GLSPASRNSV PGTQSSPYSD PDEGPSWRPL RAAPTAIVDL
TSDSDSDDSS NSPDVNNEAA FTDARHFSHQ PPSSEEDGED QGEVLSQRIG LMDVGQKRKR
QSTASSGSED VVRCQRQPNL SRKAVASVII ISSGSDTDEE PSSAVSVIVS PSSTKGHLPT
QSPSTSAHSI SSGSTTTAGS RCSDPTRILA STPPLCGNGA YNWPWLD
