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Protein

mRNA export factor

Gene

UL54

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:22334672). 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.7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi400Zinc2 Publications1
Metal bindingi479Zinc2 Publications1
Metal bindingi483Zinc2 Publications1
Metal bindingi488Zinc2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri400 – 488CHC2-type2 PublicationsAdd BLAST89

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Activation 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

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA export factor
Alternative name(s):
Immediate-early protein IE63
Infected cell protein 27
Short name:
ICP27
VMW63
Gene namesi
ORF Names:UL54
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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi500 – 512Missing : Impaired homodimerization. 1 PublicationAdd BLAST13

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001158231 – 512mRNA export factorAdd BLAST512

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16Phosphoserine; by host1 Publication1
Modified residuei18Phosphoserine; by host1 Publication1
Modified residuei114Phosphoserine; by host1 Publication1
Modified residuei138Omega-N-methylated arginine; by host1 Publication1
Modified residuei148Omega-N-methylated arginine; by host1 Publication1
Modified residuei150Omega-N-methylated arginine; by host1 Publication1

Post-translational modificationi

Methylated within the RGG box possibly by host PRMT1. When hypomethylated, ICP27 is exported to the cytoplasm earlier and more rapidly.1 Publication
Phosphorylated.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PRIDEiP10238.

PTM databases

iPTMnetiP10238.

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer (PubMed:26085142, PubMed:26062451). 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 (PubMed:12438613). Interacts with host ALYREF2 (PubMed:21253573). Interacts (via the RGG box) with host SRPK1; this interaction relocalizes SRPK1 to the nucleus and seems to alter its activity (PubMed:12660167, PubMed:19553338). Interacts with ICP4; this interaction modulates ICP4 DNA-binding activity (PubMed:8995681). Interacts with host NXF1; this interaction allows efficient export of HHV-1 early and late transcripts (PubMed:19369354).9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ICP4P083925EBI-6883946,EBI-7185388
NUP62P371983EBI-6883946,EBI-347978From a different organism.
NXF1Q9UBU94EBI-6883946,EBI-398874From a different organism.

Protein-protein interaction databases

BioGridi971451. 2 interactors.
DIPiDIP-57688N.
IntActiP10238. 4 interactors.
MINTiMINT-6732574.

Structurei

Secondary structure

1512
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi247 – 254Combined sources8
Helixi256 – 259Combined sources4
Helixi262 – 275Combined sources14
Turni279 – 282Combined sources4
Helixi293 – 296Combined sources4
Turni305 – 308Combined sources4
Helixi312 – 328Combined sources17
Helixi330 – 346Combined sources17
Helixi349 – 368Combined sources20
Helixi378 – 381Combined sources4
Helixi383 – 405Combined sources23
Helixi410 – 416Combined sources7
Helixi419 – 421Combined sources3
Helixi425 – 442Combined sources18
Beta strandi445 – 447Combined sources3
Helixi449 – 452Combined sources4
Helixi467 – 478Combined sources12
Helixi479 – 481Combined sources3
Helixi486 – 496Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KT5NMR-B103-138[»]
4YXPX-ray1.92A/B241-512[»]
5BQKX-ray2.00A/B/C242-512[»]
ProteinModelPortaliP10238.
SMRiP10238.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni104 – 112Interaction with host ALYREF9
Regioni138 – 152RGG-boxAdd BLAST15
Regioni500 – 512Important for homodimerization1 PublicationAdd BLAST13

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi5 – 17Nuclear export signalAdd BLAST13
Motifi110 – 138Nuclear localization signalAdd BLAST29

Domaini

Binds viral intronless RNAs through the RGG region.
The C-terminus is essential for homodimerization.2 Publications

Sequence similaritiesi

Belongs to the HHV-1 ICP27 protein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri400 – 488CHC2-type2 PublicationsAdd BLAST89

Keywords - Domaini

Zinc-finger

Phylogenomic databases

KOiK19443.

Family and domain databases

InterProiIPR008648. Herpes_UL69.
IPR031752. HHV-1_REF-bd.
[Graphical view]
PfamiPF05459. Herpes_UL69. 1 hit.
PF16852. HHV-1_VABD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P10238-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATDIDMLID LGLDLSDSDL DEDPPEPAES RRDDLESDSS GECSSSDEDM
60 70 80 90 100
EDPHGEDGPE PILDAARPAV RPSRPEDPGV PSTQTPRPTE RQGPNDPQPA
110 120 130 140 150
PHSVWSRLGA RRPSCSPEQH GGKVARLQPP PTKAQPARGG RRGRRRGRGR
160 170 180 190 200
GGPGAADGLS DPRRRAPRTN RNPGGPRPGA GWTDGPGAPH GEAWRGSEQP
210 220 230 240 250
DPPGGQRTRG VRQAPPPLMT LAIAPPPADP RAPAPERKAP AADTIDATTR
260 270 280 290 300
LVLRSISERA AVDRISESFG RSAQVMHDPF GGQPFPAANS PWAPVLAGQG
310 320 330 340 350
GPFDAETRRV SWETLVAHGP SLYRTFAGNP RAASTAKAMR DCVLRQENFI
360 370 380 390 400
EALASADETL AWCKMCIHHN LPLRPQDPII GTTAAVLDNL ATRLRPFLQC
410 420 430 440 450
YLKARGLCGL DELCSRRRLA DIKDIASFVF VILARLANRV ERGVAEIDYA
460 470 480 490 500
TLGVGVGEKM HFYLPGACMA GLIEILDTHR QECSSRVCEL TASHIVAPPY
510
VHGKYFYCNS LF
Length:512
Mass (Da):55,253
Last modified:July 1, 1989 - v1
Checksum:i97DF74A2B7E63A85
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti137A → V in strain: Nonneuroinvasive mutant HF10. 1
Natural varianti206Q → P in strain: Nonneuroinvasive mutant HF10. 1
Natural varianti383T → A in strain: Nonneuroinvasive mutant HF10 and 17 syn+. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14112 Genomic DNA. Translation: CAA32290.1.
DQ889502 Genomic DNA. Translation: ABI63515.1.
FJ593289 Genomic DNA. Translation: ACM62278.1.
PIRiI30089. WMBEY4.
RefSeqiYP_009137130.1. NC_001806.2.

Genome annotation databases

GeneIDi24271474.
KEGGivg:24271474.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14112 Genomic DNA. Translation: CAA32290.1.
DQ889502 Genomic DNA. Translation: ABI63515.1.
FJ593289 Genomic DNA. Translation: ACM62278.1.
PIRiI30089. WMBEY4.
RefSeqiYP_009137130.1. NC_001806.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KT5NMR-B103-138[»]
4YXPX-ray1.92A/B241-512[»]
5BQKX-ray2.00A/B/C242-512[»]
ProteinModelPortaliP10238.
SMRiP10238.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi971451. 2 interactors.
DIPiDIP-57688N.
IntActiP10238. 4 interactors.
MINTiMINT-6732574.

PTM databases

iPTMnetiP10238.

Proteomic databases

PRIDEiP10238.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24271474.
KEGGivg:24271474.

Phylogenomic databases

KOiK19443.

Family and domain databases

InterProiIPR008648. Herpes_UL69.
IPR031752. HHV-1_REF-bd.
[Graphical view]
PfamiPF05459. Herpes_UL69. 1 hit.
PF16852. HHV-1_VABD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiICP27_HHV11
AccessioniPrimary (citable) accession number: P10238
Secondary accession number(s): B9VQI3, Q09I80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 2, 2016
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.