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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 similarity1 Publication

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

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 17) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10299 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000009294 Componenti: 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

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001158061 – 248Neurovirulence factor ICP34.5Add BLAST248

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 Homo sapiens.

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP36313.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati161 – 16313
Repeati164 – 16623
Repeati167 – 16933
Repeati170 – 17243
Repeati173 – 17553

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 16Required for nucleolar localizationBy similarityAdd BLAST16
Regioni161 – 1755 X 3 AA tandem repeats of A-T-PAdd BLAST15
Regioni175 – 188Binding to PP1CABy similarityAdd BLAST14
Regioni190 – 248Important for interferon resistanceBy similarityAdd BLAST59

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi128 – 137Nuclear export signalBy similarity10
Motifi200 – 218Bipartite nuclear localization signalBy similarityAdd BLAST19

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 8Poly-Arg6
Compositional biasi10 – 175Pro-richAdd BLAST166
Compositional biasi75 – 81Poly-Asp7

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

Phylogenomic databases

KOiK19437.

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.

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.
RefSeqiYP_009137073.1. NC_001806.2.
YP_009137134.1. NC_001806.2.

Genome annotation databases

GeneIDi2703395.
2703396.
KEGGivg:2703395.
vg: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.
RefSeqiYP_009137073.1. NC_001806.2.
YP_009137134.1. NC_001806.2.

3D structure databases

ProteinModelPortaliP36313.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi2703395.
2703396.
KEGGivg:2703395.
vg:2703396.

Phylogenomic databases

KOiK19437.

Family and domain databases

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

Entry informationi

Entry nameiICP34_HHV11
AccessioniPrimary (citable) accession number: P36313
Secondary accession number(s): O12396
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 26, 2008
Last modified: September 7, 2016
This is version 67 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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.