P13202 · VIE1_HCMVA
- ProteinImmediate early protein IE1
- GeneUL123
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids491 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity).
Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417).
Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (PubMed:27903803, PubMed:34370791).
Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity).
In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity).
Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity).
Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834).
This repression is followed by phosphorylation and activation of STAT1 (By similarity).
Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity).
Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).
Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417).
Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (PubMed:27903803, PubMed:34370791).
Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity).
In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity).
Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity).
Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834).
This repression is followed by phosphorylation and activation of STAT1 (By similarity).
Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity).
Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell nucleus | |
Biological Process | bidirectional double-stranded viral DNA replication | |
Biological Process | DNA-templated viral transcription | |
Biological Process | symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint | |
Biological Process | symbiont-mediated suppression of host innate immune response | |
Biological Process | symbiont-mediated suppression of host type I interferon-mediated signaling pathway | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameImmediate early protein IE1
- Short namesIE1
- Alternative names
Gene names
Organism names
- Taxonomic lineageViruses > Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales > Orthoherpesviridae > Betaherpesvirinae > Cytomegalovirus > Cytomegalovirus humanbeta5 > Human cytomegalovirus
- Virus hosts
Accessions
- Primary accessionP13202
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with host PML-associated nuclear bodies very early post infection.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Mutagenesis | 174 | Enhanced degradation of IE1 during infection; complete loss of interference with PML sumoylation, disruption of PML-associated nuclear bodies and transactivation activity. | |||
PTM/Processing
Features
Showing features for chain, cross-link.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000115355 | 1-491 | Immediate early protein IE1 | ||
Cross-link | 450 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | |||
Post-translational modification
Sumoylated by host PML (PubMed:28250117).
Sumoylation abolishes the interaction with host STAT2 and thus the IE1-mediated repression of interferon-stimulated genes (By similarity).
Sumoylation abolishes the interaction with host STAT2 and thus the IE1-mediated repression of interferon-stimulated genes (By similarity).
Keywords
- PTM
Expression
Keywords
- Developmental stage
Interaction
Subunit
Forms homodimers (PubMed:34370791).
Interacts with human p53/TP53; this interaction inhibits p53/TP53-dependent transactivation activity. Interacts with host STAT1. Interacts with host STAT2; this interaction promotes viral growth and counteracts the antiviral interferon response. May also interact with the host STAT1-STAT2 heterodimer. Interacts with host STAT3; this interaction leads to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation (By similarity).
Interacts with host PML; this interaction inhibits host PML de novo sumoylation and probably inhibits PML regulation of type I and type II interferon-induced gene expression (PubMed:27903803, PubMed:34370791).
Interacts with host DAXX. Interacts with host SP100. Interacts with host E2F1. Interacts with host RB1. Interacts with host HDAC1; this interaction inhibits histone deacetylation and promotes viral transcription. Interacts with host HDAC2; this interaction inhibits histone deacetylation and promotes viral transcription. Interacts with host HDAC3; this interaction inhibits histone deacetylation and promotes viral transcription (By similarity).
Interacts with host PLSCR1; this interaction inhibits IE1 transactivating activity
Interacts with human p53/TP53; this interaction inhibits p53/TP53-dependent transactivation activity. Interacts with host STAT1. Interacts with host STAT2; this interaction promotes viral growth and counteracts the antiviral interferon response. May also interact with the host STAT1-STAT2 heterodimer. Interacts with host STAT3; this interaction leads to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation (By similarity).
Interacts with host PML; this interaction inhibits host PML de novo sumoylation and probably inhibits PML regulation of type I and type II interferon-induced gene expression (PubMed:27903803, PubMed:34370791).
Interacts with host DAXX. Interacts with host SP100. Interacts with host E2F1. Interacts with host RB1. Interacts with host HDAC1; this interaction inhibits histone deacetylation and promotes viral transcription. Interacts with host HDAC2; this interaction inhibits histone deacetylation and promotes viral transcription. Interacts with host HDAC3; this interaction inhibits histone deacetylation and promotes viral transcription (By similarity).
Interacts with host PLSCR1; this interaction inhibits IE1 transactivating activity
Protein-protein interaction databases
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 1-19 | Basic and acidic residues | |||
Region | 1-24 | Nuclear localization signal | |||
Region | 1-30 | Disordered | |||
Region | 132-346 | Interaction with host PML, interference with PML sumoylation and disruption of PML-associated nuclear bodies | |||
Region | 373-445 | Interaction with host STAT2 | |||
Region | 410-420 | Modulation of STAT3/STAT1 signaling | |||
Region | 410-445 | Interaction with host STAT3 | |||
Region | 421-472 | Acidic | |||
Region | 421-491 | Disordered | |||
Compositional bias | 425-442 | Acidic residues | |||
Region | 449-452 | Interaction with host SUMO1 | |||
Region | 475-491 | Chromosome-tethering domain (CTD), binding to histones | |||
Domain
The N-terminal region is required for nuclear targeting. The C-terminal 16-amino acid is termed the chromosome-tethering domain (CTD) and is required for the association of IE1, host PML and host STAT2 with the mitotic chromosomes. Targets host nucleosomes by directly binding to the acidic pocket of core histones.
Sequence similarities
Belongs to the HHV-5 IE1 protein family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length491
- Mass (Da)55,110
- Last updated1990-01-01 v1
- ChecksumCC5966B00CD8C8B4
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 1-19 | Basic and acidic residues | |||
Compositional bias | 425-442 | Acidic residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X17403 EMBL· GenBank· DDBJ | CAA35325.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21295 EMBL· GenBank· DDBJ | AAA45980.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK000394 EMBL· GenBank· DDBJ | DAA00112.1 EMBL· GenBank· DDBJ | Genomic DNA |