ICP34_HHV2H
ID ICP34_HHV2H Reviewed; 261 AA.
AC P28283;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 73.
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 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10315;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1662697; DOI=10.1099/0022-1317-72-12-3057;
RA McGeoch D.J., Cunningham C., McIntyre G., Dolan A.;
RT "Comparative sequence analysis of the long repeat regions and adjoining
RT parts of the long unique regions in the genomes of herpes simplex viruses
RT types 1 and 2.";
RL J. Gen. Virol. 72:3057-3075(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=9499055; DOI=10.1128/jvi.72.3.2010-2021.1998;
RA Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J.;
RT "The genome sequence of herpes simplex virus type 2.";
RL J. Virol. 72:2010-2021(1998).
CC -!- FUNCTION: Contributes to HSV resistance to the antiviral effects of
CC alpha/beta interferon. 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. Also down-modulates the host MHC class II proteins
CC cell surface expression. Acts as a neurovirulence factor that has a
CC profound effect on the growth of the virus in central nervous system
CC tissue, probably through its ability to maintain an environment
CC favorable for viral replication (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with human PPP1CA to form a high-molecular-weight
CC complex that dephosphorylates eIF2-alpha. Binds to proliferating cell
CC nuclear antigen (PCNA), which may release host cells from growth arrest
CC and facilitate viral replication (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250}. Host nucleus, host
CC nucleolus {ECO:0000250}. Virion {ECO:0000250}. Note=At early times in
CC infection, colocalizes with PCNA and replication proteins in cell
CC nuclei, before accumulating in the cytoplasm by 8 to 12 hours post-
CC infection. The effects on the host cell are probably mediated by de
CC novo-synthesized ICP34.5, the virion-derived population being either
CC non-functional or present in very low amounts (By similarity).
CC {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 -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}.
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DR EMBL; D10471; BAA23428.1; -; Genomic_DNA.
DR EMBL; Z86099; CAB06759.1; -; Genomic_DNA.
DR EMBL; Z86099; CAB06706.1; -; Genomic_DNA.
DR PIR; JQ1502; WMBEXE.
DR RefSeq; YP_009137150.1; NC_001798.2.
DR RefSeq; YP_009137211.1; NC_001798.2.
DR PRIDE; P28283; -.
DR DNASU; 1487286; -.
DR GeneID; 1487286; -.
DR GeneID; 1487287; -.
DR KEGG; vg:1487286; -.
DR KEGG; vg:1487287; -.
DR Proteomes; UP000001874; Genome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProt.
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.
DR InterPro; IPR019523; Prot_Pase1_reg-su15A/B_C.
DR Pfam; PF10488; PP1c_bdg; 1.
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; Reference proteome; Repeat;
KW Viral immunoevasion; Virion; Virulence.
FT CHAIN 1..261
FT /note="Neurovirulence factor ICP34.5"
FT /id="PRO_0000116339"
FT REPEAT 3..7
FT REPEAT 8..12
FT REPEAT 16..23
FT REPEAT 24..31
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..19
FT /note="Required for nucleolar localization"
FT /evidence="ECO:0000250"
FT REGION 3..12
FT /note="2 X 5 AA tandem repeats of R-R-R-G-P"
FT REGION 16..31
FT /note="2 X 8 AA tandem repeats of P-R-P-G-A-P-A-V"
FT REGION 75..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..176
FT /note="Binding to PP1CA"
FT /evidence="ECO:0000250"
FT REGION 178..261
FT /note="Important for interferon resistance"
FT /evidence="ECO:0000250"
FT REGION 223..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 128..137
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 188..206
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..16
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..33
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..123
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..241
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 261 AA; 27908 MW; 4BBD13AF3D906D71 CRC64;
MSRRRGPRRR GPRRRPRPGA PAVPRPGAPA VPRPGALPTA DSQMVPAYDS GTAVESAPAA
SSLLRRWLLV PQADDSDDAD YAGNDDAEWA NSPPSEGGGK APEAPHAAPA AACPPPPPRK
ERGPQRPLPP HLALRLRTTT EYLARLSLRR RRPPASPPAD APRGKVCFSP RVQVRHLVAW
ETAARLARRG SWARERADRD RFRRRVAAAE AVIGPCLEPE ARARARARAR AHEDGGPAEE
EEAAAAARGS SAAAGPGRRA V
