P36313 (ICP34_HHV11) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 55. History...
Names and origin
|Protein names||Recommended name:|
Neurovirulence factor ICP34.5
Infected cell protein 34.5
|Organism||Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]|
|Taxonomic identifier||10299 [NCBI]|
|Taxonomic lineage||Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||248 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Contributes to HSV resistance to the antiviral effects of alpha/beta interferon. Recruits the serine/threonine-protein phosphatase PPP1CA/PP1-alpha to dephosphorylate the translation initiation factor eIF-2A, thereby couteracting the host shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase EIF2AK2/PKR. Also down-modulates the host MHC class II proteins cell surface expression. Acts as a neurovirulence factor that has a profound effect on the growth of the virus in central nervous system tissue, probably through its ability to maintain an environment favorable for viral replication By similarity. Ref.4
Interacts with human PPP1CA to form a high-molecular-weight complex that dephosphorylates eIF2-alpha By similarity. Binds to proliferating cell nuclear antigen (PCNA), which may release host cells from growth arrest and facilitate viral replication. Ref.5
Host cytoplasm By similarity. Host nucleus › host nucleolus By similarity. Virion By similarity. Note: At early times in infection, colocalizes with PCNA and replication proteins in cell nuclei, before accumulating in the cytoplasm by 8 to 12 hours post-infection. The effects on the host cell are probably mediated by de novo-synthesized ICP34.5, the virion-derived population being either non-functional or present in very low amounts.
The triplet repeats region may play a role in modulating virus egress By similarity.
ICP34.5 is detected as early as 3 hpi prior to viral replication but reaches maximal levels late in infection. ICP34.5 gene is therefore classified as gamma-1 or leaky late gene.
The phosphatase activity of the ICP34.5-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, which inhibits viral replication By similarity.
Belongs to the PPP1R15 family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 248||248||Neurovirulence factor ICP34.5||PRO_0000115806|
|Repeat||161 – 163||3||1|
|Repeat||164 – 166||3||2|
|Repeat||167 – 169||3||3|
|Repeat||170 – 172||3||4|
|Repeat||173 – 175||3||5|
|Region||1 – 16||16||Required for nucleolar localization By similarity|
|Region||161 – 175||15||5 X 3 AA tandem repeats of A-T-P|
|Region||175 – 188||14||Binding to PP1CA By similarity|
|Region||190 – 248||59||Important for interferon resistance By similarity|
|Motif||128 – 137||10||Nuclear export signal By similarity|
|Motif||200 – 218||19||Bipartite nuclear localization signal By similarity|
|Compositional bias||3 – 8||6||Poly-Arg|
|Compositional bias||10 – 175||166||Pro-rich|
|Compositional bias||75 – 81||7||Poly-Asp|
|||"The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1."|
McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P.
J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17."|
Dolan A., McKie E., MacLean A.R., McGeoch D.J.
J. Gen. Virol. 73:971-973(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
|||"The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1."|
Perry L.J., McGeoch D.J.
J. Gen. Virol. 69:2831-2846(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2."|
Brown S.M., Harland J., MacLean A.R., Podlech J., Clements J.B.
J. Gen. Virol. 75:2367-2377(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Strain: 17syn+ and 17termA.
|||"The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34."|
Brown S.M., MacLean A.R., McKie E.A., Harland J.
J. Virol. 71:9442-9449(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCNA.
|+||Additional computationally mapped references.|
|X14112 Genomic DNA. Translation: CAA32285.1.|
X14112 Genomic DNA. Translation: CAA32348.1.
|RefSeq||NP_044600.1. NC_001806.1. |
3D structure databases
Protein-protein interaction databases
|BioGrid||971431. 12 interactions.|
|IntAct||P36313. 13 interactions.|
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR019523. Prot_Pase1_reg-su15A/B_C. |
|Pfam||PF10488. PP1c_bdg. 1 hit. |
|Accession||Primary (citable) accession number: P36313|
Secondary accession number(s): O12396
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families