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

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi400 – 4001Zinc2 Publications
Metal bindingi479 – 4791Zinc2 Publications
Metal bindingi483 – 4831Zinc2 Publications
Metal bindingi488 – 4881Zinc2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri400 – 48889CHC2-type2 PublicationsAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi500 – 51213Missing : Impaired homodimerization. 1 PublicationAdd
BLAST

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 512512mRNA export factorPRO_0000115823Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei16 – 161Phosphoserine; by host1 Publication
Modified residuei18 – 181Phosphoserine; by host1 Publication
Modified residuei114 – 1141Phosphoserine; by host1 Publication
Modified residuei138 – 1381Omega-N-methylated arginine; by host1 Publication
Modified residuei148 – 1481Omega-N-methylated arginine; by host1 Publication
Modified residuei150 – 1501Omega-N-methylated arginine; by host1 Publication

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

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 interactions.
IntActiP10238. 4 interactions.
MINTiMINT-6732574.

Structurei

Secondary structure

1
512
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi247 – 2548Combined sources
Helixi256 – 2594Combined sources
Helixi262 – 27514Combined sources
Turni279 – 2824Combined sources
Helixi293 – 2964Combined sources
Turni305 – 3084Combined sources
Helixi312 – 32817Combined sources
Helixi330 – 34617Combined sources
Helixi349 – 36820Combined sources
Helixi378 – 3814Combined sources
Helixi383 – 40523Combined sources
Helixi410 – 4167Combined sources
Helixi419 – 4213Combined sources
Helixi425 – 44218Combined sources
Beta strandi445 – 4473Combined sources
Helixi449 – 4524Combined sources
Helixi467 – 47812Combined sources
Helixi479 – 4813Combined sources
Helixi486 – 49611Combined sources

3D structure databases

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

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni104 – 1129Interaction with host ALYREF
Regioni138 – 15215RGG-boxAdd
BLAST
Regioni500 – 51213Important for homodimerization1 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi5 – 1713Nuclear export signalAdd
BLAST
Motifi110 – 13829Nuclear localization signalAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri400 – 48889CHC2-type2 PublicationsAdd
BLAST

Keywords - Domaini

Zinc-finger

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti137 – 1371A → V in strain: Nonneuroinvasive mutant HF10.
Natural varianti206 – 2061Q → P in strain: Nonneuroinvasive mutant HF10.
Natural varianti383 – 3831T → A in strain: Nonneuroinvasive mutant HF10 and 17 syn+.

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2KT5NMR-B103-138[»]
4YXPX-ray1.92A/B241-512[»]
5BQKX-ray2.00A/B/C242-512[»]
ProteinModelPortaliP10238.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi971451. 2 interactions.
IntActiP10238. 4 interactions.
MINTiMINT-6732574.

PTM databases

iPTMnetiP10238.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24271474.
KEGGivg:24271474.

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: September 7, 2016
This is version 93 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.