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Protein

Neurovirulence factor ICP34.5

Gene

RL1

Organism
Human herpesvirus 1 (strain F) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.2 Publications

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 (By similarity).By similarity
The phosphatase activity of the ICP34.5-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, which inhibits viral replication.

GO - Biological processi

Keywordsi

Biological processHost-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 F) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10304 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

  • Host cytoplasm
  • Host nucleushost nucleolus
  • 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 mediated by de novo-synthesized ICP34.5, the virion-derived population being either non-functional or present in very low amounts (By similarity).By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi134L → A: Complete loss of cytoplasmic localization; when associated with A-136. 1 Publication1
Mutagenesisi136L → A: Complete loss of cytoplasmic localization; when associated with A-134. 1 Publication1
Mutagenesisi193V → E: Loss of interferon resistance; when associated with F-195. 1 Publication1
Mutagenesisi195F → L: Loss of interferon resistance; when associated with V-193. 1 Publication1
Mutagenesisi215R → A: Decrease in nuclear localization; when associated with A-216. 1 Publication1
Mutagenesisi216R → A: Decrease in nuclear localization; when associated with A-215. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001158071 – 263Neurovirulence factor ICP34.5Add BLAST263

Interactioni

Subunit structurei

Interacts with human PPP1CA to form a high-molecular-weight complex that dephosphorylates eIF2-alpha. Binds to host PCNA, which may release host cells from growth arrest and facilitate viral replication.4 Publications

Protein-protein interaction databases

IntActiP08353. 2 interactors.
MINTiMINT-8293225.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati161 – 16311 Publication3
Repeati164 – 16621 Publication3
Repeati167 – 16931 Publication3
Repeati170 – 17241 Publication3
Repeati173 – 17551 Publication3
Repeati176 – 17861 Publication3
Repeati179 – 18171 Publication3
Repeati182 – 18481 Publication3
Repeati185 – 18791 Publication3
Repeati188 – 190101 Publication3

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 16Required for nucleolar localizationAdd BLAST16
Regioni161 – 19010 X 3 AA tandem repeats of A-T-PAdd BLAST30
Regioni190 – 203Binding to PPP1CAAdd BLAST14
Regioni205 – 263Important for interferon resistanceAdd BLAST59

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi128 – 137Nuclear export signal10
Motifi215 – 233Bipartite nuclear localization signalAdd BLAST19

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 8Poly-Arg6
Compositional biasi10 – 190Pro-richAdd BLAST181
Compositional biasi75 – 81Poly-Asp7

Domaini

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

Sequence similaritiesi

Belongs to the PPP1R15 family.Curated

Keywords - Domaini

Repeat

Family and domain databases

InterProiView protein in InterPro
IPR019523. Prot_Pase1_reg-su15A/B_C.
PfamiView protein in Pfam
PF10488. PP1c_bdg. 1 hit.

Sequencei

Sequence statusi: Complete.

P08353-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARRRRHRGP RRPRPPGPTG AVPTAQSQVT STPNSEPAVR SAPAAAPPPP
60 70 80 90 100
PASGPPPSCS LLLRQWLHVP ESASDDDDDD DWPDSPPPEP APEARPTAAA
110 120 130 140 150
PRPRSPPPGA GPGGGANPSH PPSRPFRLPP RLALRLRVTA EHLARLRLRR
160 170 180 190 200
AGGEGAPEPP ATPATPATPA TPATPATPAT PATPATPATP ARVRFSPHVR
210 220 230 240 250
VRHLVVWASA ARLARRGSWA RERADRARFR RRVAEAEAVI GPCLGPEARA
260
RALARGAGPA NSV
Length:263
Mass (Da):27,533
Last modified:October 1, 1994 - v2
Checksum:iF5084106A08A8CB1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12240 Genomic DNA. Translation: AAA45794.1. Sequence problems.
M33699 Genomic DNA. Translation: AAA45790.1.
PIRiA27768. WMBE38.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiICP34_HHV1F
AccessioniPrimary (citable) accession number: P08353
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 1, 1994
Last modified: January 7, 2015
This is version 64 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families