ICP34_HHV11
ID ICP34_HHV11 Reviewed; 248 AA.
AC P36313; O12396;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 23-FEB-2022, entry version 81.
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=ICP34.5; Synonyms=RL1;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=1321882; DOI=10.1099/0022-1317-73-4-971;
RA Dolan A., McKie E., MacLean A.R., McGeoch D.J.;
RT "Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17.";
RL J. Gen. Virol. 73:971-973(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2846760; DOI=10.1099/0022-1317-69-11-2831;
RA Perry L.J., McGeoch D.J.;
RT "The DNA sequences of the long repeat region and adjoining parts of the
RT long unique region in the genome of herpes simplex virus type 1.";
RL J. Gen. Virol. 69:2831-2846(1988).
RN [4]
RP FUNCTION.
RC STRAIN=17syn+, and 17termA;
RX PubMed=8077935; DOI=10.1099/0022-1317-75-9-2367;
RA Brown S.M., Harland J., MacLean A.R., Podlech J., Clements J.B.;
RT "Cell type and cell state determine differential in vitro growth of non-
RT neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2.";
RL J. Gen. Virol. 75:2367-2377(1994).
RN [5]
RP FUNCTION.
RX PubMed=7996163; DOI=10.1099/0022-1317-75-12-3679;
RA Brown S.M., MacLean A.R., Aitken J.D., Harland J.;
RT "ICP34.5 influences herpes simplex virus type 1 maturation and egress from
RT infected cells in vitro.";
RL J. Gen. Virol. 75:3679-3686(1994).
RN [6]
RP INTERACTION WITH PCNA.
RX PubMed=9371605; DOI=10.1128/jvi.71.12.9442-9449.1997;
RA Brown S.M., MacLean A.R., McKie E.A., Harland J.;
RT "The herpes simplex virus virulence factor ICP34.5 and the cellular protein
RT MyD116 complex with proliferating cell nuclear antigen through the 63-
RT amino-acid domain conserved in ICP34.5, MyD116, and GADD34.";
RL J. Virol. 71:9442-9449(1997).
RN [7]
RP FUNCTION, AND INTERACTION WITH HOST BECN1.
RX PubMed=18005679; DOI=10.1016/j.chom.2006.12.001;
RA Orvedahl A., Alexander D., Talloczy Z., Sun Q., Wei Y., Zhang W., Burns D.,
RA Leib D.A., Levine B.;
RT "HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy
RT protein.";
RL Cell Host Microbe 1:23-35(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH UL31; HOST C1QBP AND HOST PRKCA.
RX PubMed=27630226; DOI=10.1128/jvi.01392-16;
RA Wu S., Pan S., Zhang L., Baines J., Roller R., Ames J., Yang M., Wang J.,
RA Chen D., Liu Y., Zhang C., Cao Y., He B.;
RT "Herpes Simplex Virus 1 Induces Phosphorylation and Reorganization of Lamin
RT A/C through the gamma134.5 Protein That Facilitates Nuclear Egress.";
RL J. Virol. 90:10414-10422(2016).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST TBK1.
RX PubMed=28904192; DOI=10.1128/jvi.01156-17;
RA Manivanh R., Mehrbach J., Knipe D.M., Leib D.A.;
RT "Role of Herpes Simplex Virus 1 gamma34.5 in the Regulation of IRF3
RT Signaling.";
RL J. Virol. 91:0-0(2017).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST STING/TMEM173.
RX PubMed=30045990; DOI=10.1128/jvi.01015-18;
RA Pan S., Liu X., Ma Y., Cao Y., He B.;
RT "34.5 Protein Inhibits STING Activation That Restricts Viral Replication.";
RL J. Virol. 0:0-0(2018).
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 (PubMed:27630226). Recruits the serine/threonine protein
CC phosphatase PPP1CA/PP1-alpha to dephosphorylate the translation
CC initiation factor eIF-2A, thereby couteracting the host shutoff of
CC protein synthesis involving double-stranded RNA-dependent protein
CC kinase EIF2AK2/PKR. In turn, controls host IRF3 activation and
CC subsequently inhibits host interferon response (PubMed:28904192).
CC Controls the DNA sensing pathway by interacting with and inhibiting
CC host STING/TMEM173 (PubMed:30045990). Also down-modulates the host MHC
CC 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 (PubMed:18005679).
CC {ECO:0000269|PubMed:18005679, ECO:0000269|PubMed:27630226,
CC ECO:0000269|PubMed:28904192, ECO:0000269|PubMed:30045990,
CC ECO:0000269|PubMed:7996163, ECO:0000269|PubMed:8077935}.
CC -!- SUBUNIT: Interacts with human PPP1CA to form a high-molecular-weight
CC complex that dephosphorylates eIF2-alpha (By similarity). Binds to
CC proliferating cell nuclear antigen (PCNA), which may release host cells
CC from growth arrest and facilitate viral replication. Interacts (via N-
CC terminus) with host C1QBP and PRKCA (PubMed:27630226). Interacts with
CC protein UL31 (PubMed:27630226). Interacts with host TBK1
CC (PubMed:28904192). Interacts with host STING/TMEM173; this interaction
CC inhibits the intracellular DNA sensing pathway (PubMed:30045990).
CC Interacts with host BECN1; this interaction modulates host autophagy
CC (PubMed:18005679). {ECO:0000250|UniProtKB:P08353,
CC ECO:0000269|PubMed:18005679, ECO:0000269|PubMed:27630226,
CC ECO:0000269|PubMed:28904192, ECO:0000269|PubMed:30045990,
CC ECO:0000269|PubMed:9371605}.
CC -!- INTERACTION:
CC P36313; P62136: PPP1CA; Xeno; NbExp=4; IntAct=EBI-6149234, EBI-357253;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:P08353}.
CC Host nucleus {ECO:0000250|UniProtKB:P08353}. Host nucleus, host
CC nucleolus {ECO:0000250|UniProtKB:P08353}. Virion
CC {ECO:0000250|UniProtKB:P08353}. Note=At early times in infection,
CC colocalizes with PCNA and replication proteins in the host cell
CC nucleus, before accumulating in the host cytoplasm by 8 to 12 hours
CC post-infection. {ECO:0000250|UniProtKB:P08353}.
CC -!- DOMAIN: The triplet repeats region may play a role in modulating virus
CC egress. {ECO:0000250}.
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.
CC -!- MISCELLANEOUS: The phosphatase activity of the ICP34.5-PP1 complex
CC toward EIF2S1 is specifically inhibited by Salubrinal, which inhibits
CC viral replication. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}.
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DR EMBL; X14112; CAA32285.1; -; Genomic_DNA.
DR EMBL; X14112; CAA32348.1; -; Genomic_DNA.
DR PIR; JQ1682; JQ1682.
DR RefSeq; YP_009137073.1; NC_001806.2.
DR RefSeq; YP_009137134.1; NC_001806.2.
DR BioGRID; 971431; 12.
DR IntAct; P36313; 13.
DR MINT; P36313; -.
DR PRIDE; P36313; -.
DR GeneID; 2703395; -.
DR GeneID; 2703396; -.
DR KEGG; vg:2703395; -.
DR KEGG; vg:2703396; -.
DR Proteomes; UP000009294; Genome.
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; Reference proteome; Repeat;
KW Viral immunoevasion; Virion; Virulence.
FT CHAIN 1..248
FT /note="Neurovirulence factor ICP34.5"
FT /id="PRO_0000115806"
FT REPEAT 161..163
FT /note="1"
FT REPEAT 164..166
FT /note="2"
FT REPEAT 167..169
FT /note="3"
FT REPEAT 170..172
FT /note="4"
FT REPEAT 173..175
FT /note="5"
FT REGION 1..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..16
FT /note="Required for nucleolar localization"
FT /evidence="ECO:0000250|UniProtKB:P08353"
FT REGION 149..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..175
FT /note="5 X 3 AA tandem repeats of A-T-P"
FT REGION 175..188
FT /note="Binding to PP1CA"
FT /evidence="ECO:0000250|UniProtKB:P08353"
FT REGION 190..248
FT /note="Important for interferon resistance"
FT /evidence="ECO:0000250|UniProtKB:P08353"
FT MOTIF 128..137
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P08353"
FT MOTIF 200..218
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08353"
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"
SQ SEQUENCE 248 AA; 26196 MW; BF216520CB379478 CRC64;
MARRRRHRGP RRPRPPGPTG AVPTAQSQVT STPNSEPAVR SAPAAAPPPP PAGGPPPSCS
LLLRQWLHVP ESASDDDDDD DWPDSPPPEP APEARPTAAA PRPRPPPPGV GPGGGADPSH
PPSRPFRLPP RLALRLRVTA EHLARLRLRR AGGEGAPEPP ATPATPATPA TPATPARVRF
SPHVRVRHLV VWASAARLAR RGSWARERAD RARFRRRVAE AEAVIGPCLG PEARARALAR
GAGPANSV
