P10238 (ICP27_HHV11) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcriptional regulator ICP27

Alternative name(s):
Immediate-early protein IE63
Infected cell protein 27
Short name=ICP27
VMW63

Gene names

ORF Names:

UL54

Organism

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]

Taxonomic identifier

10299 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 1

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	512 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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.14 Ref.15 Ref.17
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.12 Ref.14 Ref.15 Ref.16 Ref.17
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.13 Phosphorylated. Ref.8
Sequence similarities	Belongs to the HHV-1 ICP27 protein family.

Ontologies

Keywords
Biological process	Activation of host NF-kappa-B 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 component	Host cytoplasm Host nucleus
Developmental stage	Early protein
Domain	Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
Molecular function	Activator
PTM	Methylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation 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 regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 512	512	Transcriptional regulator ICP27		PRO_0000115823
Regions
	Zinc finger	468 – 512	45	Potential
	Region	5 – 17	13	Nuclear export signal
	Region	104 – 112	9	Interaction with host ALYREF
	Region	110 – 138	29	Nuclear localization signal
	Region	138 – 152	15	RGG-box
Amino acid modifications
	Modified residue	16	1	Phosphoserine; by host Probable
	Modified residue	18	1	Phosphoserine; by host Probable
	Modified residue	114	1	Phosphoserine; by host Probable
	Modified residue	138	1	Omega-N-methylated arginine; by host Probable
	Modified residue	148	1	Omega-N-methylated arginine; by host Probable
	Modified residue	150	1	Omega-N-methylated arginine; by host Probable
Natural variations
	Natural variant	137	1	A → V in strain: Nonneuroinvasive mutant HF10.
	Natural variant	206	1	Q → P in strain: Nonneuroinvasive mutant HF10.
	Natural variant	383	1	T → A in strain: Nonneuroinvasive mutant HF10 and 17 syn+.

Sequences

	Sequence		Length	Mass (Da)
	P10238 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 97DF74A2B7E63A85	FASTA	512	55,253
	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

References

	« Hide 'large scale' referencesShow '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: INTERACTION WITH HOST SRPK1, FUNCTION IN HOST SHUTOFF.
[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: INTERACTION WITH HOST RPB1.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
PIR	WMBEY4. I30089.
RefSeq	NP_044657.1. NC_001806.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-6732574.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	2703426.
Phylogenomic databases
ProtClustDB	CLSP2510173.
Family and domain databases
InterPro	IPR008648. Herpes_UL69. [Graphical view]
Pfam	PF05459. Herpes_UL69. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ICP27_HHV11

Accession

Primary (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:	April 3, 2013
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program