ID   E4OR1_ADE09             Reviewed;         125 AA.
AC   P89079;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   14-DEC-2022, entry version 87.
DE   RecName: Full=E4-ORF1;
DE            EC=3.6.1.23;
DE   AltName: Full=Early E4 14.0 kDa protein;
DE   AltName: Full=ORF1;
DE   AltName: Full=Probable dUTPase E4 ORF1;
GN   Name=E4;
OS   Human adenovirus D serotype 9 (HAdV-9) (Human adenovirus 9).
OC   Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC   Rowavirales; Adenoviridae; Mastadenovirus; Human mastadenovirus D.
OX   NCBI_TaxID=10527;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8738606; DOI=10.1007/bf01806078;
RA   Javier R.T., Shenk T.;
RT   "Mammary tumors induced by human adenovirus type 9: a role for the viral
RT   early region 4 gene.";
RL   Breast Cancer Res. Treat. 39:57-67(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Isolate ATCC VR-1086 / Hicks / V-209-003-014;
RA   Buettner W.H., Veres-Molnar S.K.;
RT   "Adenovirus type 9, complete sequence.";
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION AS ONCOGENE.
RX   PubMed=8189528; DOI=10.1128/jvi.68.6.3917-3924.1994;
RA   Javier R.T.;
RT   "Adenovirus type 9 E4 open reading frame 1 encodes a transforming protein
RT   required for the production of mammary tumors in rats.";
RL   J. Virol. 68:3917-3924(1994).
RN   [4]
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF 34-PHE--VAL-41; LEU-89; PHE-91;
RP   ALA-122 AND 123-THR--VAL-125.
RX   PubMed=9151828; DOI=10.1128/jvi.71.6.4385-4394.1997;
RA   Weiss R.S., Gold M.O., Vogel H., Javier R.T.;
RT   "Mutant adenovirus type 9 E4 ORF1 genes define three protein regions
RT   required for transformation of CREF cells.";
RL   J. Virol. 71:4385-4394(1997).
RN   [5]
RP   INTERACTION WITH HUMAN MPDZ, AND MUTAGENESIS OF ALA-122; 123-THR--VAL-125
RP   AND LEU-124.
RX   PubMed=11000240; DOI=10.1128/jvi.74.20.9680-9693.2000;
RA   Lee S.S., Glaunsinger B., Mantovani F., Banks L., Javier R.T.;
RT   "Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus
RT   E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins.";
RL   J. Virol. 74:9680-9693(2000).
CC   -!- FUNCTION: Plays a key role in virus oncogenecity in animals. Binds and
CC       sequesters human MUPP1/MPDZ protein in the cytoplasm, preventing it
CC       from playing a role in cellular proliferation regulation. Induces cell
CC       transformation, probably by inactivating MPDZ protein.
CC       {ECO:0000269|PubMed:8189528}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dUTP + H2O = diphosphate + dUMP + H(+); Xref=Rhea:RHEA:10248,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:61555, ChEBI:CHEBI:246422; EC=3.6.1.23;
CC   -!- SUBUNIT: Binds to human MPDZ.
CC   -!- INTERACTION:
CC       P89079; Q62696: Dlg1; Xeno; NbExp=4; IntAct=EBI-7401124, EBI-389325;
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:9151828}.
CC   -!- SIMILARITY: Belongs to the dUTPase family. {ECO:0000305}.
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DR   EMBL; S82508; AAB37504.1; -; Genomic_DNA.
DR   EMBL; AJ854486; CAI05991.1; -; Genomic_DNA.
DR   SMR; P89079; -.
DR   DIP; DIP-44835N; -.
DR   ELM; P89079; -.
DR   IntAct; P89079; 3.
DR   MINT; P89079; -.
DR   Proteomes; UP000118285; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004170; F:dUTP diphosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR   Gene3D; 2.70.40.10; -; 1.
DR   InterPro; IPR029054; dUTPase-like.
DR   InterPro; IPR036157; dUTPase-like_sf.
DR   Pfam; PF00692; dUTPase; 1.
DR   SUPFAM; SSF51283; dUTPase-like; 1.
PE   1: Evidence at protein level;
KW   Early protein; Host cytoplasm; Host-virus interaction; Hydrolase;
KW   Nucleotide metabolism; Oncogene.
FT   CHAIN           1..125
FT                   /note="E4-ORF1"
FT                   /id="PRO_0000221784"
FT   MOTIF           122..125
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         34..41
FT                   /note="FHIPPHGV->IHIPPQGA: Complete loss of
FT                   transformation."
FT                   /evidence="ECO:0000269|PubMed:9151828"
FT   MUTAGEN         89
FT                   /note="L->Q: Complete loss of transformation."
FT                   /evidence="ECO:0000269|PubMed:9151828"
FT   MUTAGEN         91
FT                   /note="F->S: Complete loss of transformation."
FT                   /evidence="ECO:0000269|PubMed:9151828"
FT   MUTAGEN         122
FT                   /note="A->D: Partial loss of transformation. Complete loss
FT                   of binding to MPDZ. Localizes aberrantly in the nucleus."
FT                   /evidence="ECO:0000269|PubMed:11000240,
FT                   ECO:0000269|PubMed:9151828"
FT   MUTAGEN         123..125
FT                   /note="TLV->P: Complete loss of transformation. Complete
FT                   loss of binding to MPDZ. Localizes aberrantly in the
FT                   nucleus."
FT                   /evidence="ECO:0000269|PubMed:11000240,
FT                   ECO:0000269|PubMed:9151828"
FT   MUTAGEN         124
FT                   /note="L->P: Partial loss of transformation. Partial loss
FT                   of binding to MPDZ. Localizes aberrantly in the nucleus."
FT                   /evidence="ECO:0000269|PubMed:11000240"
SQ   SEQUENCE   125 AA;  14041 MW;  75792A75E484BC09 CRC64;
     MAESLYAFID SPGGIAPVQE GTSNRYTFFC PESFHIPPHG VVLLHLKVSV LVPTGYQGRF
     MALNDYHARD ILTQSDVIFA GRRQELTVLL FNHTDRFLYV RKGHPVGTLL LERVIFPSVK
     IATLV
//