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P36313

- ICP34_HHV11

UniProt

P36313 - ICP34_HHV11

Protein

Neurovirulence factor ICP34.5

Gene

RL1

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 58 (01 Oct 2014)
      Sequence version 2 (26 Feb 2008)
      Previous versions | rss
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    Functioni

    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.By similarity

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. modulation by virus of host PP1 activity Source: UniProtKB-KW
    2. pathogenesis Source: UniProtKB-KW
    3. suppression by virus of host autophagy Source: UniProtKB-KW
    4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW

    Keywords - Biological processi

    Host-virus interaction, Inhibition of host autophagy by virus, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host RLR pathway by virus, Modulation of host PP1 activity by virus, Viral immunoevasion, Virulence

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Neurovirulence factor ICP34.5
    Alternative name(s):
    Infected cell protein 34.5
    protein gamma(1)34.5
    Gene namesi
    Name:RL1
    Synonyms:ICP34.5
    OrganismiHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
    Taxonomic identifieri10299 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000009294: Genome

    Subcellular locationi

    Host cytoplasm By similarity. Host nucleushost 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.

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell nucleolus Source: UniProtKB-SubCell
    3. virion Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 248248Neurovirulence factor ICP34.5PRO_0000115806Add
    BLAST

    Interactioni

    Subunit structurei

    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.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PPP1CAP621364EBI-6149234,EBI-357253From a different organism.

    Protein-protein interaction databases

    BioGridi971431. 12 interactions.
    IntActiP36313. 13 interactions.
    MINTiMINT-6175580.

    Structurei

    3D structure databases

    ProteinModelPortaliP36313.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati161 – 16331
    Repeati164 – 16632
    Repeati167 – 16933
    Repeati170 – 17234
    Repeati173 – 17535

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 1616Required for nucleolar localizationBy similarityAdd
    BLAST
    Regioni161 – 175155 X 3 AA tandem repeats of A-T-PAdd
    BLAST
    Regioni175 – 18814Binding to PP1CABy similarityAdd
    BLAST
    Regioni190 – 24859Important for interferon resistanceBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi128 – 13710Nuclear export signalBy similarity
    Motifi200 – 21819Bipartite nuclear localization signalBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi3 – 86Poly-Arg
    Compositional biasi10 – 175166Pro-richAdd
    BLAST
    Compositional biasi75 – 817Poly-Asp

    Domaini

    The triplet repeats region may play a role in modulating virus egress.By similarity

    Sequence similaritiesi

    Belongs to the PPP1R15 family.Curated

    Keywords - Domaini

    Repeat

    Family and domain databases

    InterProiIPR019523. Prot_Pase1_reg-su15A/B_C.
    [Graphical view]
    PfamiPF10488. PP1c_bdg. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P36313-1 [UniParc]FASTAAdd to Basket

    « Hide

    MARRRRHRGP RRPRPPGPTG AVPTAQSQVT STPNSEPAVR SAPAAAPPPP    50
    PAGGPPPSCS LLLRQWLHVP ESASDDDDDD DWPDSPPPEP APEARPTAAA 100
    PRPRPPPPGV GPGGGADPSH PPSRPFRLPP RLALRLRVTA EHLARLRLRR 150
    AGGEGAPEPP ATPATPATPA TPATPARVRF SPHVRVRHLV VWASAARLAR 200
    RGSWARERAD RARFRRRVAE AEAVIGPCLG PEARARALAR GAGPANSV 248
    Length:248
    Mass (Da):26,196
    Last modified:February 26, 2008 - v2
    Checksum:iBF216520CB379478
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14112 Genomic DNA. Translation: CAA32285.1.
    X14112 Genomic DNA. Translation: CAA32348.1.
    PIRiJQ1682.
    RefSeqiNP_044600.1. NC_001806.1.
    NP_044661.1. NC_001806.1.

    Genome annotation databases

    GeneIDi2703395.
    2703396.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14112 Genomic DNA. Translation: CAA32285.1 .
    X14112 Genomic DNA. Translation: CAA32348.1 .
    PIRi JQ1682.
    RefSeqi NP_044600.1. NC_001806.1.
    NP_044661.1. NC_001806.1.

    3D structure databases

    ProteinModelPortali P36313.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 971431. 12 interactions.
    IntActi P36313. 13 interactions.
    MINTi MINT-6175580.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 2703395.
    2703396.

    Family and domain databases

    InterProi IPR019523. Prot_Pase1_reg-su15A/B_C.
    [Graphical view ]
    Pfami PF10488. PP1c_bdg. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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].
    2. "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.
    3. "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].
    4. "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.
    5. "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.

    Entry informationi

    Entry nameiICP34_HHV11
    AccessioniPrimary (citable) accession number: P36313
    Secondary accession number(s): O12396
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: February 26, 2008
    Last modified: October 1, 2014
    This is version 58 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3