Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Neurovirulence factor ICP34.5

Gene

RL1

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: Annotation score: 4 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 (By similarity).By similarity

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
Complete GO annotation...

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
Complete GO annotation...

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

        10         20         30         40         50
MARRRRHRGP RRPRPPGPTG AVPTAQSQVT STPNSEPAVR SAPAAAPPPP
60 70 80 90 100
PAGGPPPSCS LLLRQWLHVP ESASDDDDDD DWPDSPPPEP APEARPTAAA
110 120 130 140 150
PRPRPPPPGV GPGGGADPSH PPSRPFRLPP RLALRLRVTA EHLARLRLRR
160 170 180 190 200
AGGEGAPEPP ATPATPATPA TPATPARVRF SPHVRVRHLV VWASAARLAR
210 220 230 240
RGSWARERAD RARFRRRVAE AEAVIGPCLG PEARARALAR GAGPANSV
Length:248
Mass (Da):26,196
Last modified:February 26, 2008 - v2
Checksum:iBF216520CB379478
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP36313.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi2703395.
2703396.

Family and domain databases

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

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: January 7, 2015
This is version 60 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

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 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.