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P10238 (ICP27_HHV11) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
mRNA export factor
Alternative name(s):
Immediate-early protein IE63
Infected cell protein 27
Short name=ICP27
VMW63
Gene names
ORF Names:UL54
OrganismHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]
Taxonomic identifier10299 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length512 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Multifunctional regulator of the expression of viral genes that contributes to the shutoff of host protein synthesis and mediates nuclear export of viral intronless mRNAs. Early in infection, this immediate early (EI) protein mediates the inhibition of cellular splicing. This results in the accumulation of unprocessed 3'end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off early after virus infection. Later in the infection, it helps recruit cellular RNA polymerase II to viral replication sites and promotes the nuclear export of viral intronless mRNAs by interacting with mRNAs and host NXF1/TAP. ICP27 binds to NUP62 which may provide facilitated viral mRNA export and may indirectly compete with some host cell transport receptors for binding and inhibit cellular nucleocytoplasmic transport pathways. Also stimulates translation of viral transcripts. Repression of host gene expression blocks the cell cycle at the G1 phase and prevents apoptosis. Seems to silence the 3' splice site of the promyelocytic leukemia (PML) intron 7a, thereby switching PML isoforms from PML-II to PML-V. This could be linked to the accelerated mRNA export induced by ICP27 which might not provide sufficient time for PML pre-mRNA to be spliced in the nucleus. Ref.7 Ref.9 Ref.11 Ref.12 Ref.15 Ref.16 Ref.18

Subunit structure

Interacts with host RBP1; this interaction facilitates the RNA polymerase recruitment to viral transcription sites. Interacts (via the RGG box) with host ALYREF/THOC4; this interaction recruits ALYREF to viral replication compartments and probably directs viral mRNA to the TAP/NFX1 pathway. Interacts (via the RGG box) with host SRPK1; this interaction relocalizes SRPK1 to the nucleus and seems to alter its activity. Interacts with ICP4; this interaction modulates ICP4 DNA-binding activity. Interacts with host NXF1; this interaction allows efficient export of HHV-1 early and late transcripts. Ref.5 Ref.10 Ref.11 Ref.15 Ref.16 Ref.17 Ref.18

Subcellular location

Host cytoplasm. Host nucleus. Note: Shuttles between the nucleus and the cytoplasm. Ref.6

Domain

Binds viral intronless RNAs through the RGG region.

Post-translational modification

Methylated within the RGG box possibly by host PRMT1. When hypomethylated, ICP27 is exported to the cytoplasm earlier and more rapidly. Ref.14

Phosphorylated. Ref.8

Sequence similarities

Belongs to the HHV-1 ICP27 protein family.

Caution

A role in degradation of host polymerase has been suggested in PubMed 16537625, but this could be a consequence of binding to immature mRNAs simultaneously to transcription by the polymerase.

Ontologies

Keywords
   Biological processActivation of host NF-kappa-B by virus
Eukaryotic host gene expression shutoff by virus
G1/S host cell cycle checkpoint dysregulation by virus
Host gene expression shutoff by virus
Host mRNA suppression by virus
Host-virus interaction
Inhibition of host pre-mRNA processing by virus
Modulation of host cell cycle by virus
Transcription
Transcription regulation
   Cellular componentHost cytoplasm
Host nucleus
   Developmental stageEarly protein
   DomainZinc-finger
   LigandMetal-binding
RNA-binding
Zinc
   Molecular functionActivator
   PTMMethylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation by virus of host NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host G1/S transition checkpoint

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host mRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.18Ref.5. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ICP4P083925EBI-6883946,EBI-7185388
NUP62P371983EBI-6883946,EBI-347978From a different organism.
NXF1Q9UBU94EBI-6883946,EBI-398874From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 512512mRNA export factor
PRO_0000115823

Regions

Zinc finger468 – 51245 Potential
Region5 – 1713Nuclear export signal
Region104 – 1129Interaction with host ALYREF
Region110 – 13829Nuclear localization signal
Region138 – 15215RGG-box

Amino acid modifications

Modified residue161Phosphoserine; by host Probable
Modified residue181Phosphoserine; by host Probable
Modified residue1141Phosphoserine; by host Probable
Modified residue1381Omega-N-methylated arginine; by host Probable
Modified residue1481Omega-N-methylated arginine; by host Probable
Modified residue1501Omega-N-methylated arginine; by host Probable

Natural variations

Natural variant1371A → V in strain: Nonneuroinvasive mutant HF10.
Natural variant2061Q → P in strain: Nonneuroinvasive mutant HF10.
Natural variant3831T → A in strain: Nonneuroinvasive mutant HF10 and 17 syn+.

Sequences

Sequence LengthMass (Da)Tools
P10238 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 97DF74A2B7E63A85

FASTA51255,253
        10         20         30         40         50         60 
MATDIDMLID LGLDLSDSDL DEDPPEPAES RRDDLESDSS GECSSSDEDM EDPHGEDGPE 

        70         80         90        100        110        120 
PILDAARPAV RPSRPEDPGV PSTQTPRPTE RQGPNDPQPA PHSVWSRLGA RRPSCSPEQH 

       130        140        150        160        170        180 
GGKVARLQPP PTKAQPARGG RRGRRRGRGR GGPGAADGLS DPRRRAPRTN RNPGGPRPGA 

       190        200        210        220        230        240 
GWTDGPGAPH GEAWRGSEQP DPPGGQRTRG VRQAPPPLMT LAIAPPPADP RAPAPERKAP 

       250        260        270        280        290        300 
AADTIDATTR LVLRSISERA AVDRISESFG RSAQVMHDPF GGQPFPAANS PWAPVLAGQG 

       310        320        330        340        350        360 
GPFDAETRRV SWETLVAHGP SLYRTFAGNP RAASTAKAMR DCVLRQENFI EALASADETL 

       370        380        390        400        410        420 
AWCKMCIHHN LPLRPQDPII GTTAAVLDNL ATRLRPFLQC YLKARGLCGL DELCSRRRLA 

       430        440        450        460        470        480 
DIKDIASFVF VILARLANRV ERGVAEIDYA TLGVGVGEKM HFYLPGACMA GLIEILDTHR 

       490        500        510 
QECSSRVCEL TASHIVAPPY VHGKYFYCNS LF 

« Hide

References

« Hide 'large scale' references
[1]"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].
[2]"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 [LARGE SCALE GENOMIC DNA].
[3]"Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus."
Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.
Microbes Infect. 9:142-149(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Nonneuroinvasive mutant HF10.
[4]"Herpes simplex virus type 1 bacterial artificial chromosome."
Cunningham C., Davison A.J.
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 17 syn+.
[5]"Physical and functional interactions between herpes simplex virus immediate-early proteins ICP4 and ICP27."
Panagiotidis C.A., Lium E.K., Silverstein S.J.
J. Virol. 71:1547-1557(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ICP4.
[6]"The herpes simplex virus immediate-early protein ICP27 shuttles between nucleus and cytoplasm."
Mears W.E., Rice S.A.
Virology 242:128-137(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif."
Sandri-Goldin R.M.
Genes Dev. 12:868-879(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Analysis of the phosphorylation sites of herpes simplex virus type 1 regulatory protein ICP27."
Zhi Y., Sandri-Goldin R.M.
J. Virol. 73:3246-3257(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-16; SER-18 AND SER-114.
[9]"Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step."
Bryant H.E., Wadd S.E., Lamond A.I., Silverstein S.J., Clements J.B.
J. Virol. 75:4376-4385(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"ICP27 interacts with the RNA export factor Aly/REF to direct herpes simplex virus type 1 intronless mRNAs to the TAP export pathway."
Chen I.-H.B., Sciabica K.S., Sandri-Goldin R.M.
J. Virol. 76:12877-12889(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST ALYREF/THOC4.
[11]"ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation."
Sciabica K.S., Dai Q.J., Sandri-Goldin R.M.
EMBO J. 22:1608-1619(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST SRPK1.
[12]"ICP27 interacts with the C-terminal domain of RNA polymerase II and facilitates its recruitment to herpes simplex virus 1 transcription sites, where it undergoes proteasomal degradation during infection."
Dai-Ju J.Q., Li L., Johnson L.A., Sandri-Goldin R.M.
J. Virol. 80:3567-3581(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"The many roles of the regulatory protein ICP27 during herpes simplex virus infection."
Sandri-Goldin R.M.
Front. Biosci. 13:5241-5256(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication."
Souki S.K., Gershon P.D., Sandri-Goldin R.M.
J. Virol. 83:5309-5320(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT ARG-138; ARG-148 AND ARG-150.
[15]"Arginine methylation of the ICP27 RGG box regulates the functional interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1 infection."
Souki S.K., Sandri-Goldin R.M.
J. Virol. 83:8970-8975(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST SRPK1, FUNCTION.
[16]"The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein Aly/REF appears to be dispensable."
Johnson L.A., Li L., Sandri-Goldin R.M.
J. Virol. 83:6335-6346(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST NXF1, FUNCTION.
[17]"Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57."
Tunnicliffe R.B., Hautbergue G.M., Kalra P., Jackson B.R., Whitehouse A., Wilson S.A., Golovanov A.P.
PLoS Pathog. 7:E1001244-E1001244(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST ALYREF.
[18]"Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through Nup62, inhibiting host nucleocytoplasmic transport pathways."
Malik P., Tabarraei A., Kehlenbach R.H., Korfali N., Iwasawa R., Graham S.V., Schirmer E.C.
J. Biol. Chem. 287:12277-12292(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST NUP62, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14112 Genomic DNA. Translation: CAA32290.1.
DQ889502 Genomic DNA. Translation: ABI63515.1.
FJ593289 Genomic DNA. Translation: ACM62278.1.
PIRWMBEY4. I30089.
RefSeqNP_044657.1. NC_001806.1.

3D structure databases

ProteinModelPortalP10238.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid971451. 1 interaction.
IntActP10238. 4 interactions.
MINTMINT-6732574.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2703426.

Family and domain databases

InterProIPR008648. Herpes_UL69.
[Graphical view]
PfamPF05459. Herpes_UL69. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameICP27_HHV11
AccessionPrimary (citable) accession number: P10238
Secondary accession number(s): B9VQI3, Q09I80
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families