ICP34_HHV1F
ID ICP34_HHV1F Reviewed; 263 AA.
AC P08353;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 23-FEB-2022, entry version 79.
DE RecName: Full=Neurovirulence factor ICP34.5;
DE AltName: Full=Infected cell protein 34.5;
DE AltName: Full=protein gamma(1)34.5;
GN Name=RL1; Synonyms=ICP34.5;
OS Human herpesvirus 1 (strain F) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10304;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3003394; DOI=10.1128/jvi.57.2.629-637.1986;
RA Chou J., Roizman B.;
RT "The terminal a sequence of the herpes simplex virus genome contains the
RT promoter of a gene located in the repeat sequences of the L component.";
RL J. Virol. 57:629-637(1986).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=2154589; DOI=10.1128/jvi.64.3.1014-1020.1990;
RA Chou J., Roizman B.;
RT "The herpes simplex virus 1 gene for ICP34.5, which maps in inverted
RT repeats, is conserved in several limited-passage isolates but not in strain
RT 17syn+.";
RL J. Virol. 64:1014-1020(1990).
RN [3]
RP FUNCTION, AND INTERACTION WITH HUMAN PPP1CA.
RX PubMed=9023344; DOI=10.1073/pnas.94.3.843;
RA He B., Gross M., Roizman B.;
RT "The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein
RT phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic
RT translation initiation factor 2 and preclude the shutoff of protein
RT synthesis by double-stranded RNA-activated protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:843-848(1997).
RN [4]
RP INTERACTION WITH HUMAN PPP1CA.
RX PubMed=9694816; DOI=10.1074/jbc.273.33.20737;
RA He B., Gross M., Roizman B.;
RT "The gamma134.5 protein of herpes simplex virus 1 has the structural and
RT functional attributes of a protein phosphatase 1 regulatory subunit and is
RT present in a high molecular weight complex with the enzyme in infected
RT cells.";
RL J. Biol. Chem. 273:20737-20743(1998).
RN [5]
RP MUTAGENESIS OF VAL-193 AND PHE-195.
RX PubMed=11882996; DOI=10.1006/viro.2001.1148;
RA Cheng G., Brett M.-E., He B.;
RT "Val193 and Phe195 of the gamma 1 34.5 protein of herpes simplex virus 1
RT are required for viral resistance to interferon-alpha/beta.";
RL Virology 290:115-120(2001).
RN [6]
RP FUNCTION.
RX PubMed=12072498; DOI=10.1128/jvi.76.14.6974-6986.2002;
RA Trgovcich J., Johnson D., Roizman B.;
RT "Cell surface major histocompatibility complex class II proteins are
RT regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes
RT simplex virus 1.";
RL J. Virol. 76:6974-6986(2002).
RN [7]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT SIGNAL,
RP AND MUTAGENESIS OF LEU-134; LEU-136; ARG-215 AND ARG-216.
RX PubMed=12186925; DOI=10.1128/jvi.76.18.9434-9445.2002;
RA Cheng G., Brett M.-E., He B.;
RT "Signals that dictate nuclear, nucleolar, and cytoplasmic shuttling of the
RT gamma(1)34.5 protein of herpes simplex virus type 1.";
RL J. Virol. 76:9434-9445(2002).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HOST PCNA.
RX PubMed=12907392; DOI=10.1080/13550280390218788;
RA Harland J., Dunn P., Cameron E., Conner J., Brown S.M.;
RT "The herpes simplex virus (HSV) protein ICP34.5 is a virion component that
RT forms a DNA-binding complex with proliferating cell nuclear antigen and HSV
RT replication proteins.";
RL J. Neurovirol. 9:477-488(2003).
RN [9]
RP REGION OF TRIPLET REPEATS.
RX PubMed=16099898; DOI=10.1099/vir.0.81033-0;
RA Jing X., He B.;
RT "Characterization of the triplet repeats in the central domain of the
RT gamma134.5 protein of herpes simplex virus 1.";
RL J. Gen. Virol. 86:2411-2419(2005).
RN [10]
RP INTERACTION WITH PPP1CA.
RX PubMed=15705855; DOI=10.1126/science.1101902;
RA Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D.,
RA Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J.;
RT "A selective inhibitor of eIF2alpha dephosphorylation protects cells from
RT ER stress.";
RL Science 307:935-939(2005).
CC -!- FUNCTION: Plays essential roles in viral nuclear egress to mediate
CC capsid transit across the nuclear membrane and also in the inhibition
CC of host immune response. Facilitates nuclear egress cooperatively with
CC host C1QBP and protein kinase C/PKC to induce lamin A/C phosphorylation
CC and subsequent reorganization. In turn, lamina disassembles and nuclear
CC egress occurs. Recruits the serine/threonine protein phosphatase
CC PPP1CA/PP1-alpha to dephosphorylate the translation initiation factor
CC eIF-2A, thereby couteracting the host shutoff of protein synthesis
CC involving double-stranded RNA-dependent protein kinase EIF2AK2/PKR. In
CC turn, controls host IRF3 activation and subsequently inhibits host
CC interferon response. Controls the DNA sensing pathway by interacting
CC with and inhibiting host STING/TMEM173. Also down-modulates the host
CC MHC class II proteins cell surface expression. Acts as a neurovirulence
CC factor that has a profound effect on the growth of the virus in central
CC nervous system tissue, by interqcting with host BECN1 and thereby
CC antagonizing the host autophagy response.
CC {ECO:0000250|UniProtKB:P36313, ECO:0000269|PubMed:12072498,
CC ECO:0000269|PubMed:9023344}.
CC -!- SUBUNIT: Interacts with human PPP1CA to form a high-molecular-weight
CC complex that dephosphorylates eIF2-alpha (PubMed:9023344,
CC PubMed:9694816, PubMed:15705855). Binds to proliferating cell nuclear
CC antigen (PCNA), which may release host cells from growth arrest and
CC facilitate viral replication (PubMed:12907392). Interacts (via N-
CC terminus) with host C1QBP and PRKCA. Interacts with protein UL31.
CC Interacts with host TBK1. Interacts with host STING/TMEM173; this
CC interaction inhibits the intracellular DNA sensing pathway. Interacts
CC with host BECN1; this interaction modulates host autophagy (By
CC similarity). {ECO:0000250|UniProtKB:P36313,
CC ECO:0000269|PubMed:12907392, ECO:0000269|PubMed:15705855,
CC ECO:0000269|PubMed:9023344, ECO:0000269|PubMed:9694816}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:12186925}.
CC Host nucleus {ECO:0000269|PubMed:12186925}. Host nucleus, host
CC nucleolus {ECO:0000269|PubMed:12186925}. Virion. Note=At early times in
CC infection, colocalizes with PCNA and replication proteins in the host
CC cell nucleus, before accumulating in the host cytoplasm by 8 to 12
CC hours post-infection. {ECO:0000269|PubMed:12186925}.
CC -!- DOMAIN: The triplet repeats region may play a role in modulating virus
CC egress.
CC -!- MISCELLANEOUS: ICP34.5 is detected as early as 3 hpi prior to viral
CC replication but reaches maximal levels late in infection. ICP34.5 gene
CC is therefore classified as gamma-1 or leaky late gene (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: The phosphatase activity of the ICP34.5-PP1 complex
CC toward EIF2S1 is specifically inhibited by Salubrinal, which inhibits
CC viral replication.
CC -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}.
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; M12240; AAA45794.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M33699; AAA45790.1; -; Genomic_DNA.
DR PIR; A27768; WMBE38.
DR ELM; P08353; -.
DR IntAct; P08353; 1.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039521; P:suppression by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host autophagy by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host RLR pathway by virus;
KW Modulation of host PP1 activity by virus; Repeat; Viral immunoevasion;
KW Virion; Virulence.
FT CHAIN 1..263
FT /note="Neurovirulence factor ICP34.5"
FT /id="PRO_0000115807"
FT REPEAT 161..163
FT /note="1"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 164..166
FT /note="2"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 167..169
FT /note="3"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 170..172
FT /note="4"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 173..175
FT /note="5"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 176..178
FT /note="6"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 179..181
FT /note="7"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 182..184
FT /note="8"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 185..187
FT /note="9"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REPEAT 188..190
FT /note="10"
FT /evidence="ECO:0000269|PubMed:16099898"
FT REGION 1..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..16
FT /note="Required for nucleolar localization"
FT /evidence="ECO:0000269|PubMed:12186925"
FT REGION 149..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..190
FT /note="10 X 3 AA tandem repeats of A-T-P"
FT REGION 190..203
FT /note="Binding to PPP1CA"
FT REGION 205..263
FT /note="Important for interferon resistance"
FT MOTIF 128..137
FT /note="Nuclear export signal"
FT MOTIF 215..233
FT /note="Bipartite nuclear localization signal"
FT COMPBIAS 21..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..57
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..128
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..185
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 134
FT /note="L->A: Complete loss of cytoplasmic localization;
FT when associated with A-136."
FT /evidence="ECO:0000269|PubMed:12186925"
FT MUTAGEN 136
FT /note="L->A: Complete loss of cytoplasmic localization;
FT when associated with A-134."
FT /evidence="ECO:0000269|PubMed:12186925"
FT MUTAGEN 193
FT /note="V->E: Loss of interferon resistance; when associated
FT with F-195."
FT /evidence="ECO:0000269|PubMed:11882996"
FT MUTAGEN 195
FT /note="F->L: Loss of interferon resistance; when associated
FT with V-193."
FT /evidence="ECO:0000269|PubMed:11882996"
FT MUTAGEN 215
FT /note="R->A: Decrease in nuclear localization; when
FT associated with A-216."
FT /evidence="ECO:0000269|PubMed:12186925"
FT MUTAGEN 216
FT /note="R->A: Decrease in nuclear localization; when
FT associated with A-215."
FT /evidence="ECO:0000269|PubMed:12186925"
SQ SEQUENCE 263 AA; 27533 MW; F5084106A08A8CB1 CRC64;
MARRRRHRGP RRPRPPGPTG AVPTAQSQVT STPNSEPAVR SAPAAAPPPP PASGPPPSCS
LLLRQWLHVP ESASDDDDDD DWPDSPPPEP APEARPTAAA PRPRSPPPGA GPGGGANPSH
PPSRPFRLPP RLALRLRVTA EHLARLRLRR AGGEGAPEPP ATPATPATPA TPATPATPAT
PATPATPATP ARVRFSPHVR VRHLVVWASA ARLARRGSWA RERADRARFR RRVAEAEAVI
GPCLGPEARA RALARGAGPA NSV