ICP34_HHV1N
ID ICP34_HHV1N Reviewed; 245 AA.
AC P37319;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 23-FEB-2022, entry version 57.
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 MGH-10) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=37107;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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).
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}.
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. 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:P08353,
CC ECO:0000250|UniProtKB:P36313}.
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 (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. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}.
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DR EMBL; M33700; AAA45791.1; -; Genomic_DNA.
DR PRIDE; P37319; -.
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 3: Inferred from homology;
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..245
FT /note="Neurovirulence factor ICP34.5"
FT /id="PRO_0000115809"
FT REPEAT 155..157
FT /note="1"
FT REPEAT 158..160
FT /note="2"
FT REPEAT 161..163
FT /note="3"
FT REPEAT 164..166
FT /note="4"
FT REPEAT 167..169
FT /note="5"
FT REPEAT 170..172
FT /note="6"
FT REGION 1..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..17
FT /note="Required for nucleolar localization"
FT /evidence="ECO:0000250"
FT REGION 143..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 155..172
FT /note="6 X 3 AA tandem repeats of A-T-P"
FT REGION 172..185
FT /note="Binding to PP1CA"
FT /evidence="ECO:0000250"
FT REGION 187..245
FT /note="Important for interferon resistance"
FT /evidence="ECO:0000250"
FT MOTIF 122..131
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 197..215
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 22..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..122
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 153..167
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 245 AA; 25981 MW; 55ADA50AB1B8CA11 CRC64;
MARRRRRHRG PRRPRPPGPT GAVPTAQSQV TSTPNSEPVV RSAPAAGGPP PSCSLLLRQW
LHVPESASDD DDDDDWPDSP PPEPAPEARP TAAAPRPRSP PPGAGPGGGA NPSHPPSRPF
RLPPRLALRL RVTAEHLARL RLRRAGGEGA PKPPATPATP ATPATPATPA TPARVRFSPH
VRVRHLVVWA SAARLARRGS WARERADRAR FRRRVAEAEA VIGPCLGPEA RARALARGAG
PANSV
