VIE2_HCMVA
ID VIE2_HCMVA Reviewed; 580 AA.
AC P19893; Q7M6S5;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 23-FEB-2022, entry version 92.
DE RecName: Full=Viral transcription factor IE2;
DE Short=IE2;
DE AltName: Full=Protein UL122;
GN Name=UL122;
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 [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 [2]
RP GENOME REANNOTATION, AND SEQUENCE REVISION.
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 [3]
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 [4]
RP IDENTIFICATION.
RX PubMed=15452216; DOI=10.1128/jvi.78.20.10960-10966.2004;
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RT "Identification of proteins in human cytomegalovirus (HCMV) particles: the
RT HCMV proteome.";
RL J. Virol. 78:10960-10966(2004).
RN [5]
RP ERRATUM OF PUBMED:15452216.
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RL J. Virol. 78:13395-13395(2004).
RN [6]
RP INTERACTION WITH HOST CREB1.
RX PubMed=7666507; DOI=10.1128/jvi.69.10.6030-6037.1995;
RA Lang D., Gebert S., Arlt H., Stamminger T.;
RT "Functional interaction between the human cytomegalovirus 86-kilodalton IE2
RT protein and the cellular transcription factor CREB.";
RL J. Virol. 69:6030-6037(1995).
RN [7]
RP FUNCTION IN HOST CELL CYCLE MODULATION.
RX PubMed=10516036; DOI=10.1128/jvi.73.11.9274-9283.1999;
RA Wiebusch L., Hagemeier C.;
RT "Human cytomegalovirus 86-kilodalton IE2 protein blocks cell cycle
RT progression in G(1).";
RL J. Virol. 73:9274-9283(1999).
RN [8]
RP FUNCTION, SUMOYLATION AT LYS-175 AND LYS-180, AND REGION.
RX PubMed=19812159; DOI=10.1128/jvi.01525-09;
RA Berndt A., Hofmann-Winkler H., Tavalai N., Hahn G., Stamminger T.;
RT "Importance of covalent and noncovalent SUMO interactions with the major
RT human cytomegalovirus transactivator IE2p86 for viral infection.";
RL J. Virol. 83:12881-12894(2009).
RN [9]
RP INTERACTION WITH HOST TAF12.
RX PubMed=20519406; DOI=10.1128/jvi.00459-10;
RA Kim E.T., Kim Y.E., Huh Y.H., Ahn J.H.;
RT "Role of noncovalent SUMO binding by the human cytomegalovirus IE2
RT transactivator in lytic growth.";
RL J. Virol. 84:8111-8123(2010).
RN [10]
RP INTERACTION WITH HOST MCM3.
RX PubMed=20545442; DOI=10.4149/av_2010_02_125;
RA Song Y.J., Stinski M.F.;
RT "Human cytomegalovirus IE86 protein binds to cellular Mcm3 protein but does
RT not inhibit its binding to the Epstein-Barr virus oriP in U373MG-p220.2
RT cells.";
RL Acta Virol. 54:125-130(2010).
CC -!- FUNCTION: Stimulates viral early and late gene expression and thus play
CC a crucial role in the regulation of productive infection. In addition,
CC activates quiescent cells to reenter the cell cycle and up-regulates
CC several E2F-responsive genes, which are responsible for pushing the
CC cell into S phase. In S-phase, inhibits cellular DNA synthesis and
CC blocks further cell cycle progression. {ECO:0000269|PubMed:10516036,
CC ECO:0000269|PubMed:19812159}.
CC -!- SUBUNIT: Interacts with host SUMO-modified form of TATA-binding protein
CC (TBP)-associated factor 12/TAF12 in a SIM-dependent manner; this
CC interaction increases the transactivation activity of IE2. Interacts
CC with host CHAF1A. Interacts with several components of the host
CC transcriptional machinery including TBP, TF2B and CREB1. Interacts with
CC host DNA replication licensing factor MCM3.
CC {ECO:0000269|PubMed:20519406, ECO:0000269|PubMed:20545442,
CC ECO:0000269|PubMed:7666507}.
CC -!- SUBCELLULAR LOCATION: Host nucleus. Note=Colocalizes with host PML-
CC associated nuclear bodies.
CC -!- DOMAIN: The SUMO-interacting motif (SIM) is required for efficient
CC transactivation function. {ECO:0000269|PubMed:19812159}.
CC -!- PTM: Sumoylated. The sumoylation is necessary for efficient replication
CC of the virus and thus for the function of this viral transcription
CC factor. {ECO:0000269|PubMed:19812159}.
CC -!- SIMILARITY: Belongs to the HHV-5 IE2 protein family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA35324.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X17403; CAA35324.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK000394; DAA00111.1; -; Genomic_DNA.
DR PIR; S09889; EDBEM4.
DR PDB; 6K5R; NMR; -; B=195-206.
DR PDB; 6K5T; NMR; -; B=195-206.
DR PDBsum; 6K5R; -.
DR PDBsum; 6K5T; -.
DR SMR; P19893; -.
DR ELM; P19893; -.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR InterPro; IPR010855; Cytomega_IE1/IE2.
DR InterPro; IPR005028; Herpes_IE2_3.
DR Pfam; PF07340; Herpes_IE1; 1.
DR Pfam; PF03361; Herpes_IE2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Early protein;
KW G0/G1 host cell cycle checkpoint dysregulation by virus;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW Host-virus interaction; Isopeptide bond; Metal-binding;
KW Modulation of host cell cycle by virus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..580
FT /note="Viral transcription factor IE2"
FT /id="PRO_0000115351"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..208
FT /note="Non-covalent SUMO1 binding region (SIM)"
FT REGION 206..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..138
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 215..240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19812159"
FT CROSSLNK 180
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19812159"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:6K5R"
SQ SEQUENCE 580 AA; 62875 MW; 41D1753A02A077ED CRC64;
MESSAKRKMD PDNPDEGPSS KVPRPETPVT KATTFLQTML RKEVNSQLSL GDPLFPELAE
ESLKTFEQVT EDCNENPEKD VLAELGDILA QAVNHAGIDS SSTGPTLTTH SCSVSSAPLN
KPTPTSVAVT NTPLPGASAT PELSPRKKPR KTTRPFKVII KPPVPPAPIM LPLIKQEDIK
PEPDFTIQYR NKIIDTAGCI VISDSEEEQG EEVETRGATA SSPSTGSGTP RVTSPTHPLS
QMNHPPLPDP LGRPDEDSSS SSSSSCSSAS DSESESEEMK CSSGGGASVT SSHHGRGGFG
GAASSSLLSC GHQSSGGAST GPRKKKSKRI SELDNEKVRN IMKDKNTPFC TPNVQTRRGR
VKIDEVSRMF RNTNRSLEYK NLPFTIPSMH QVLDEAIKAC KTMQVNNKGI QIIYTRNHEV
KSEVDAVRCR LGTMCNLALS TPFLMEHTMP VTHPPEVAQR TADACNEGVK AAWSLKELHT
HQLCPRSSDY RNMIIHAATP VDLLGALNLC LPLMQKFPKQ VMVRIFSTNQ GGFMLPIYET
AAKAYAVGQF EQPTETPPED LDTLSLAIEA AIQDLRNKSQ
