ICP27_HCMVA
ID ICP27_HCMVA Reviewed; 744 AA.
AC P16749; Q7M6M4;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=mRNA export factor ICP27 homolog;
GN ORFNames=UL69;
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.
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 FUNCTION IN CELL CYCLE ARREST.
RX PubMed=9847373; DOI=10.1128/jvi.73.1.676-683.1999;
RA Lu M., Shenk T.;
RT "Human cytomegalovirus UL69 protein induces cells to accumulate in G1 phase
RT of the cell cycle.";
RL J. Virol. 73:676-683(1999).
RN [4]
RP FUNCTION.
RX PubMed=8189530; DOI=10.1128/jvi.68.6.3943-3954.1994;
RA Winkler M., Rice S.A., Stamminger T.;
RT "UL69 of human cytomegalovirus, an open reading frame with homology to
RT ICP27 of herpes simplex virus, encodes a transactivator of gene
RT expression.";
RL J. Virol. 68:3943-3954(1994).
RN [5]
RP TEGUMENT.
RX PubMed=8971028; DOI=10.1128/jvi.70.12.8984-8987.1996;
RA Winkler M., Stamminger T.;
RT "A specific subform of the human cytomegalovirus transactivator protein
RT pUL69 is contained within the tegument of virus particles.";
RL J. Virol. 70:8984-8987(1996).
RN [6]
RP ERRATUM OF PUBMED:8971028.
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 [7]
RP VIRION.
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 [8]
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 [9]
RP INTERACTION WITH HOST DDX39A AND DDX39B.
RX PubMed=16478985; DOI=10.1128/mcb.26.5.1631-1643.2006;
RA Lischka P., Toth Z., Thomas M., Mueller R., Stamminger T.;
RT "The UL69 transactivator protein of human cytomegalovirus interacts with
RT DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of
RT unspliced RNA.";
RL Mol. Cell. Biol. 26:1631-1643(2006).
RN [10]
RP PHOSPHORYLATION BY HOST CDK1; CDK7 AND CDK9.
RX PubMed=19179338; DOI=10.1074/jbc.m805693200;
RA Rechter S., Scott G.M., Eickhoff J., Zielke K., Auerochs S., Muller R.,
RA Stamminger T., Rawlinson W.D., Marschall M.;
RT "Cyclin-dependent kinases phosphorylate the cytomegalovirus RNA Export
RT Protein pUL69 and modulate its nuclear localization and activity.";
RL J. Biol. Chem. 284:8605-8613(2009).
RN [11]
RP PHOSPHORYLATION BY UL97.
RX PubMed=19218201; DOI=10.1099/vir.0.005827-0;
RA Thomas M., Rechter S., Milbradt J., Auerochs S., Muller R., Stamminger T.,
RA Marschall M.;
RT "Cytomegaloviral protein kinase pUL97 interacts with the nuclear mRNA
RT export factor pUL69 to modulate its intranuclear localization and
RT activity.";
RL J. Gen. Virol. 90:567-578(2009).
RN [12]
RP INTERACTION WITH HOST EIF4A1 AND PABPC1.
RX PubMed=20133758; DOI=10.1073/pnas.0914856107;
RA Aoyagi M., Gaspar M., Shenk T.E.;
RT "Human cytomegalovirus UL69 protein facilitates translation by associating
RT with the mRNA cap-binding complex and excluding 4EBP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2640-2645(2010).
RN [13]
RP INTERACTION WITH HOST SUPT6H, AND FUNCTION.
RX PubMed=22171252; DOI=10.1128/jvi.06776-11;
RA Cygnar D., Hagemeier S., Kronemann D., Bresnahan W.A.;
RT "The cellular protein SPT6 is required for efficient replication of human
RT cytomegalovirus.";
RL J. Virol. 86:2011-2020(2012).
RN [14]
RP FUNCTION, INTERACTION WITH HOST DDX39B AND PRMT6, SUBCELLULAR LOCATION, AND
RP METHYLATION.
RX PubMed=26178996; DOI=10.1128/jvi.01399-15;
RA Thomas M., Sonntag E., Mueller R., Schmidt S., Zielke B., Fossen T.,
RA Stamminger T.;
RT "pUL69 of human cytomegalovirus recruits the cellular protein arginine
RT methyltransferase 6 via a domain that is crucial for mRNA export and
RT efficient viral replication.";
RL J. Virol. 89:9601-9615(2015).
RN [15]
RP SUBUNIT.
RX PubMed=29921674; DOI=10.1128/mbio.01112-18;
RA Tunnicliffe R.B., Collins R.F., Ruiz Nivia H.D., Sandri-Goldin R.M.,
RA Golovanov A.P.;
RT "The ICP27 Homology Domain of the Human Cytomegalovirus Protein UL69 Adopts
RT a Dimer-of-Dimers Structure.";
RL MBio 9:0-0(2018).
CC -!- FUNCTION: Immediate early (EI) protein that plays many roles during
CC productive infection including regulation of host cell cycle
CC progression, regulation of viral gene expression or nuclear export of
CC intronless viral RNAs. Acts as a transcriptional transactivator via
CC interaction with the cellular transcription elongation factor SUPT6H
CC (PubMed:22171252). In addition, acts as a post-transcriptional
CC transactivator that mediates the nuclear export of unspliced mRNAs via
CC interaction with DDX39B, a component of the cellular mRNA export
CC machinery (PubMed:16478985, PubMed:26178996).
CC {ECO:0000269|PubMed:16478985, ECO:0000269|PubMed:22171252,
CC ECO:0000269|PubMed:26178996, ECO:0000269|PubMed:8189530,
CC ECO:0000269|PubMed:9847373}.
CC -!- SUBUNIT: Self-associates and forms a tetramer (PubMed:29921674).
CC Interacts with host DDX39A and DDX39B; these interactions are required
CC for UL69 function in mRNA export (PubMed:26178996). Interacts with host
CC SUPT6H (PubMed:22171252). Interacts with host EIF4A1 and PABPC1
CC (PubMed:20133758). Interacts with host PRMT6.
CC {ECO:0000269|PubMed:16478985, ECO:0000269|PubMed:20133758,
CC ECO:0000269|PubMed:22171252, ECO:0000269|PubMed:26178996,
CC ECO:0000269|PubMed:29921674}.
CC -!- SUBCELLULAR LOCATION: Virion tegument. Virion. Host nucleus
CC {ECO:0000269|PubMed:26178996}. Host cytoplasm. Note=Shuttles between
CC host nucleus and cytoplasm. {ECO:0000269|PubMed:26178996}.
CC -!- PTM: Phosphorylated by UL97 and host CDK1, CDK7 and CD9.
CC Phosphorylation by CDKs impacts on UL69 nuclear localization and
CC activity (By similarity). {ECO:0000250}.
CC -!- PTM: Arginine methylated via N-terminal arginine motif.
CC {ECO:0000269|PubMed:26178996}.
CC -!- SIMILARITY: Belongs to the HHV-1 ICP27 protein family. {ECO:0000305}.
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DR EMBL; X17403; CAA35384.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00164.1; -; Genomic_DNA.
DR PIR; S09832; QQBEA7.
DR DIP; DIP-59209N; -.
DR IntAct; P16749; 20.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; 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; IPR008648; ICP27-like.
DR Pfam; PF05459; Herpes_UL69; 1.
PE 1: Evidence at protein level;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host cytoplasm;
KW Host nucleus; Host-virus interaction; Metal-binding; Methylation;
KW Modulation of host cell cycle by virus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Virion; Virion tegument; Zinc;
KW Zinc-finger.
FT CHAIN 1..744
FT /note="mRNA export factor ICP27 homolog"
FT /id="PRO_0000115835"
FT ZN_FING 387..501
FT /note="CHC2-type"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT REGION 1..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 580..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..703
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 704..719
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 494
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 496
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 501
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
SQ SEQUENCE 744 AA; 82678 MW; D0566B2009EB5828 CRC64;
MELHSRGRHD APSLSSLSER ERRARRARRF CLDYEPVPRK FRRERSPTSP STRNGAAASE
HHLAEDTVGA ASHHHRPCVP ARRPRYSKDD DTEGDPDHYP PPLPPSSRHA LGGTGGHIIM
GTAGFRGGHR ASSSFKRRVA ASASVPLNPH YGKSYDNDDG EPHHHGGDST HLRRRVPSCP
TTFGSSHPSS ANNHHGSSAG PQQQQMLALI DDELDAMDED ELQQLSRLIE KKKRARLQRG
AASSGTSPSS TSPVYDLQRY TAESLRLAPY PADLKVPTAF PQDHQPRGRI LLSHDELMHT
DYLLHIRQQF DWLEEPLLRK LVVEKIFAVY NAPNLHTLLA IIDETLSYMK YHHLHGLPVN
PHDPYLETVG GMRQLLFNKL NNLDLGCILD HQDGWGDHCS TLKRLVKKPG QMSAWLRDDV
CDLQKRPPET FSQPMHRAMA YVCSFSRVAV SLRRRALQVT GTPQFFDQFD TNNAMGTYRC
GAVSDLILGA LQCHECQNEM CELRIQRALA PYRFMIAYCP FDEQSLLDLT VFAGTTTTTA
SNHATAGGQQ RGGDQIHPTD EQYANMESRT DPATLTAYDK KDREGSHRHP SPMIAAAPPA
QPPSQPQQHY SEGELEEDED SDDASSQDLV RATDRHGDTV VYKTTAVPPS PPAPLAGVRS
HRGELNLMTP SPSHGGSPPQ VPHKQPIIPV QSANGNHSTT ATQQQQPPPP PPPPPVPQED
DSVVMRCQTP DYEDMLCYSD DMDD
