VIE1_HCMVA
ID VIE1_HCMVA Reviewed; 491 AA.
AC P13202; Q7M6S4;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 02-JUN-2021, entry version 77.
DE RecName: Full=Immediate early protein IE1;
DE Short=IE1;
DE AltName: Full=55 kDa immediate-early protein 1;
DE AltName: Full=IE1p72 {ECO:0000303|PubMed:28250117};
DE AltName: Full=IE72 {ECO:0000250|UniProtKB:P03169};
GN Name=UL123;
OS Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10360;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2986374; DOI=10.1016/0168-1702(85)90242-4;
RA Akrigg A., Wilkinson G.W.G., Oram J.D.;
RT "The structure of the major immediate early gene of human cytomegalovirus
RT strain AD169.";
RL Virus Res. 2:107-121(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT "Analysis of the protein-coding content of the sequence of human
RT cytomegalovirus strain AD169.";
RL Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN [3]
RP GENOME REANNOTATION.
RX PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RT "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT cytomegalovirus genome.";
RL J. Gen. Virol. 84:17-28(2003).
RN [4]
RP ERRATUM OF PUBMED:12533697.
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RL J. Gen. Virol. 84:1053-1053(2003).
RN [5]
RP FUNCTION.
RX PubMed=23903834; DOI=10.1128/jvi.01197-13;
RA Reitsma J.M., Sato H., Nevels M., Terhune S.S., Paulus C.;
RT "Human cytomegalovirus IE1 protein disrupts interleukin-6 signaling by
RT sequestering STAT3 in the nucleus.";
RL J. Virol. 87:10763-10776(2013).
RN [6]
RP FUNCTION.
RX PubMed=27466417; DOI=10.1128/jvi.00741-16;
RA Arend K.C., Ziehr B., Vincent H.A., Moorman N.J.;
RT "Multiple Transcripts Encode Full-Length Human Cytomegalovirus IE1 and IE2
RT Proteins during Lytic Infection.";
RL J. Virol. 90:8855-8865(2016).
RN [7]
RP SUMOYLATION BY HOST PML.
RX PubMed=28250117; DOI=10.1128/jvi.02335-16;
RA Reuter N., Schilling E.M., Scherer M., Mueller R., Stamminger T.;
RT "The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for
RT SUMOylation of the Major Immediate Early Protein IE1 of Human
RT Cytomegalovirus.";
RL J. Virol. 91:0-0(2017).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST PML.
RX PubMed=27903803; DOI=10.1128/jvi.02049-16;
RA Schilling E.M., Scherer M., Reuter N., Schweininger J., Muller Y.A.,
RA Stamminger T.;
RT "The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-
RT Mediated Intrinsic Immunity via the Inhibition of PML De Novo
RT SUMOylation.";
RL J. Virol. 91:0-0(2017).
RN [9]
RP MUTAGENESIS OF LEU-174, AND FUNCTION.
RX PubMed=26559840; DOI=10.1128/jvi.01973-15;
RA Scherer M., Otto V., Stump J.D., Klingl S., Mueller R., Reuter N.,
RA Muller Y.A., Sticht H., Stamminger T.;
RT "Characterization of Recombinant Human Cytomegaloviruses Encoding IE1
RT Mutants L174P and 1-382 Reveals that Viral Targeting of PML Bodies Perturbs
RT both Intrinsic and Innate Immune Responses.";
RL J. Virol. 90:1190-1205(2016).
CC -!- FUNCTION: Plays an important role in transactivating viral early genes
CC as well as activating its own promoter, probably by altering the viral
CC chromatin structure (By similarity). Expression of IE1 and IE2 proteins
CC is critical for the establishment of lytic infection and reactivation
CC from viral latency (PubMed:27466417). Disrupts PML-associated ND10
CC nuclear bodies by interfering with host PML and SP100 sumoylation
CC thereby altering the regulation of type I and type II interferon-
CC induced gene expression (Probable) (PubMed:27903803). Promotes
CC efficient viral growth by interacting with and directing host SP100 to
CC degradation, leading to enhanced acetylation level of histones (By
CC similarity). In addition, functions in counteracting the host innate
CC antiviral response. Inhibits the type I interferon pathway by directly
CC interacting with and sequestrating host STAT2 (By similarity). Also
CC targets type II interferon pathway by repressing IL6- and STAT3 target
CC genes (By similarity). Repression of STAT3 genes is due to STAT3
CC nuclear accumulation and disruption of IL6-induced STAT3
CC phosphorylation by IE1 (PubMed:23903834). This repression is followed
CC by phosphorylation and activation of STAT1 (By similarity). Inhibits
CC host ISG transcription by sequestering host ISGF3 in a PML- and
CC STAT2- binding dependent manner (By similarity). Alters host cell cycle
CC progression, probably through its interaction with host E2F1 or RB1
CC that overcomes the RB1-mediated repression of E2F-responsive promoters
CC (By similarity). {ECO:0000250|UniProtKB:P03169,
CC ECO:0000269|PubMed:23903834, ECO:0000269|PubMed:27466417,
CC ECO:0000269|PubMed:27903803, ECO:0000305|PubMed:26559840}.
CC -!- SUBUNIT: Interacts with human p53/TP53; this interaction inhibits
CC p53/TP53-dependent transactivation activity. Interacts with host STAT1.
CC Interacts with host STAT2; this interaction promotes viral growth and
CC counteracts the antiviral interferon response. May also interact with
CC the host STAT1-STAT2 heterodimer. Interacts with host STAT3; this
CC interaction leads to STAT3 nuclear accumulation and disruption of IL6-
CC induced STAT3 phosphorylation (By similarity). Interacts with host PML;
CC this interaction inhibits host PML de novo sumoylation and probably
CC inhibits PML regulation of type I and type II interferon-induced gene
CC expression (PubMed:27903803). Interacts with host DAXX. Interacts with
CC host SP100. Interacts with host E2F1. Interacts with host RB1.
CC Interacts with host HDAC1; this interaction inhibits histone
CC deacetylation and promotes viral transcription. Interacts with host
CC HDAC2; this interaction inhibits histone deacetylation and promotes
CC viral transcription. Interacts with host HDAC3; this interaction
CC inhibits histone deacetylation and promotes viral transcription (By
CC similarity). {ECO:0000250|UniProtKB:P03169,
CC ECO:0000269|PubMed:27903803}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P03169}.
CC Note=Colocalizes with host PML-associated nuclear bodies very early
CC post infection. {ECO:0000250|UniProtKB:P03169}.
CC -!- DOMAIN: The N-terminal region is required for nuclear targeting. The C-
CC terminal 16-amino acid is termed the chromosome-tethering domain (CTD)
CC and is required for the association of IE1, host PML and host STAT2
CC with the mitotic chromosomes. Targets host nucleosomes by directly
CC binding to the acidic pocket of core histones.
CC {ECO:0000250|UniProtKB:P03169}.
CC -!- PTM: Sumoylated by host PML (PubMed:28250117). Sumoylation abolishes
CC the interaction with host STAT2 and thus the IE1-mediated repression of
CC interferon-stimulated genes (By similarity).
CC {ECO:0000250|UniProtKB:P03169, ECO:0000269|PubMed:28250117}.
CC -!- SIMILARITY: Belongs to the HHV-5 IE1 protein family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X17403; CAA35325.1; -; Genomic_DNA.
DR EMBL; M21295; AAA45980.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00112.1; -; Genomic_DNA.
DR PIR; S09890; EDBEM5.
DR PDB; 6TGZ; X-ray; 3.20 A; F=14-382.
DR PDBsum; 6TGZ; -.
DR SMR; P13202; -.
DR ELM; P13202; -.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039686; P:bidirectional double-stranded viral DNA replication; IDA:UniProtKB.
DR GO; GO:0039695; P:DNA-templated viral transcription; ISS:UniProtKB.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR010855; Cytomega_IE1/IE2.
DR Pfam; PF07340; Herpes_IE1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus; Isopeptide bond;
KW Modulation of host cell cycle by virus; Reference proteome;
KW Ubl conjugation; Viral immunoevasion.
FT CHAIN 1..491
FT /note="Immediate early protein IE1"
FT /id="PRO_0000115355"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..24
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 132..346
FT /note="Interaction with host PML, interference with PML
FT sumoylation and disruption of PML-associated nuclear
FT bodies"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 373..445
FT /note="Interaction with host STAT2"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 410..445
FT /note="Interaction with host STAT3"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 410..420
FT /note="Modulation of STAT3/STAT1 signaling"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 421..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..472
FT /note="Acidic"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 449..452
FT /note="Interaction with host SUMO1"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT REGION 475..491
FT /note="Chromosome-tethering domain (CTD), binding to
FT histones"
FT /evidence="ECO:0000250|UniProtKB:P03169"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..442
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 450
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT MUTAGEN 174
FT /note="L->P: Enhanced degradation of IE1 during infection;
FT complete loss of interference with PML sumoylation,
FT disruption of PML-associated nuclear bodies and
FT transactivation activity."
FT /evidence="ECO:0000269|PubMed:26559840"
FT HELIX 28..47
FT /evidence="ECO:0007829|PDB:6TGZ"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 66..75
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 81..136
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 164..218
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 243..262
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 264..326
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 332..354
FT /evidence="ECO:0007829|PDB:6TGZ"
FT HELIX 368..381
FT /evidence="ECO:0007829|PDB:6TGZ"
SQ SEQUENCE 491 AA; 55110 MW; CC5966B00CD8C8B4 CRC64;
MESSAKRKMD PDNPDEGPSS KVPRPETPVT KATTFLQTML RKEVNSQLSL GDPLFPELAE
ESLKTFEQVT EDCNENPEKD VLAELVKQIK VRVDMVRHRI KEHMLKKYTQ TEEKFTGAFN
MMGGCLQNAL DILDKVHEPF EEMKCIGLTM QSMYENYIVP EDKREMWMAC IKELHDVSKG
AANKLGGALQ AKARAKKDEL RRKMMYMCYR NIEFFTKNSA FPKTTNGCSQ AMAALQNLPQ
CSPDEIMAYA QKIFKILDEE RDKVLTHIDH IFMDILTTCV ETMCNEYKVT SDACMMTMYG
GISLLSEFCR VLCCYVLEET SVMLAKRPLI TKPEVISVMK RRIEEICMKV FAQYILGADP
LRVCSPSVDD LRAIAEESDE EEAIVAYTLA TAGVSSSDSL VSPPESPVPA TIPLSSVIVA
ENSDQEESEQ SDEEEEEGAQ EEREDTVSVK SEPVSEIEEV APEEEEDGAE EPTASGGKST
HPMVTRSKAD Q
