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   04-NOV-2026, entry version 90.
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; Orthoherpesviridae; Betaherpesvirinae; Cytomegalovirus;
OC   Cytomegalovirus humanbeta5; Human 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).
RN   [10] {ECO:0007744|PDB:6TGZ}
RP   X-RAY CRYSTALLOGRAPHY, FUNCTION, INTERACTION WITH HOST PML, SUBCELLULAR
RP   LOCATION, AND SUBUNIT.
RX   PubMed=34370791; DOI=10.1371/journal.ppat.1009863;
RA   Schweininger J., Scherer M., Rothemund F., Schilling E.M., Worz S.,
RA   Stamminger T., Muller Y.A.;
RT   "Cytomegalovirus immediate-early 1 proteins form a structurally distinct
RT   protein class with adaptations determining cross-species barriers.";
RL   PLoS Pathog. 17:1-31(2021).
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 (PubMed:27903803, PubMed:34370791). 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:0000269|PubMed:34370791,
CC       ECO:0000305|PubMed:26559840}.
CC   -!- SUBUNIT: Forms homodimers (PubMed:34370791). Interacts with human
CC       p53/TP53; this interaction inhibits p53/TP53-dependent transactivation
CC       activity. Interacts with host STAT1. Interacts with host STAT2; this
CC       interaction promotes viral growth and counteracts the antiviral
CC       interferon response. May also interact with the host STAT1-STAT2
CC       heterodimer. Interacts with host STAT3; this interaction leads to STAT3
CC       nuclear accumulation and disruption of IL6-induced STAT3
CC       phosphorylation (By similarity). Interacts with host PML; this
CC       interaction inhibits host PML de novo sumoylation and probably inhibits
CC       PML regulation of type I and type II interferon-induced gene expression
CC       (PubMed:27903803, PubMed:34370791). Interacts with host DAXX. Interacts
CC       with 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). Interacts with host PLSCR1; this interaction inhibits IE1
CC       transactivating activity. {ECO:0000250|UniProtKB:P03169,
CC       ECO:0000269|PubMed:27903803, ECO:0000269|PubMed:34370791}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:34370791}.
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}.
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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   SMR; P13202; -.
DR   ELM; P13202; -.
DR   PRO; PR:P13202; -.
DR   Proteomes; UP000008992; Segment.
DR   GO; GO:0042025; C:host cell nucleus; EXP:UniProtKB.
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:symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint; IEA:UniProtKB-KW.
DR   GO; GO:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:symbiont-mediated suppression 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;
KW   Interferon antiviral system evasion; 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..11
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        423..444
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        455..470
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..259
FT                   /evidence="ECO:0007829|PDB:6TGZ"
FT   HELIX           260..264
FT                   /evidence="ECO:0007829|PDB:6TGZ"
FT   HELIX           265..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
//