ID   E4RF5_ADE02             Reviewed;         150 AA.
AC   P03238;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2013, sequence version 2.
DT   29-SEP-2021, entry version 59.
DE   RecName: Full=Early 4 ORF6/7 control protein;
DE            Short=E4-ORF6/7;
DE   AltName: Full=Early E4 17 kDa protein;
OS   Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2).
OC   Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC   Rowavirales; Adenoviridae; Mastadenovirus.
OX   NCBI_TaxID=10515;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6985482; DOI=10.1093/nar/9.16.4023;
RA   Herisse J., Rigolet M., Dupont de Dinechin S., Galibert F.;
RT   "Nucleotide sequence of adenovirus 2 DNA fragment encoding for the
RT   carboxylic region of the fiber protein and the entire E4 region.";
RL   Nucleic Acids Res. 9:4023-4042(1981).
RN   [2]
RP   INTERACTION WITH HOST E2F.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=2532611; DOI=10.1101/gad.3.11.1699;
RA   Huang M.M., Hearing P.;
RT   "The adenovirus early region 4 open reading frame 6/7 protein regulates the
RT   DNA binding activity of the cellular transcription factor, E2F, through a
RT   direct complex.";
RL   Genes Dev. 3:1699-1710(1989).
RN   [3]
RP   INTERACTION WITH HOST E2F.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=1832724; DOI=10.1128/jvi.65.10.5364-5373.1991;
RA   Neill S.D., Nevins J.R.;
RT   "Genetic analysis of the adenovirus E4 6/7 trans activator: interaction
RT   with E2F and induction of a stable DNA-protein complex are critical for
RT   activity.";
RL   J. Virol. 65:5364-5373(1991).
RN   [4]
RP   FUNCTION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=8289811; DOI=10.1128/mcb.14.2.1333-1346.1994;
RA   Obert S., O'Connor R.J., Schmid S., Hearing P.;
RT   "The adenovirus E4-6/7 protein transactivates the E2 promoter by inducing
RT   dimerization of a heteromeric E2F complex.";
RL   Mol. Cell. Biol. 14:1333-1346(1994).
RN   [5]
RP   FUNCTION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=10666238; DOI=10.1128/jvi.74.5.2084-2093.2000;
RA   Schaley J., O'Connor R.J., Taylor L.J., Bar-Sagi D., Hearing P.;
RT   "Induction of the cellular E2F-1 promoter by the adenovirus E4-6/7
RT   protein.";
RL   J. Virol. 74:2084-2093(2000).
RN   [6]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=15681431; DOI=10.1128/jvi.79.4.2301-2308.2005;
RA   Schaley J.E., Polonskaia M., Hearing P.;
RT   "The adenovirus E4-6/7 protein directs nuclear localization of E2F-4 via an
RT   arginine-rich motif.";
RL   J. Virol. 79:2301-2308(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=15769610; DOI=10.2741/1604;
RA   Weitzman M.D.;
RT   "Functions of the adenovirus E4 proteins and their impact on viral
RT   vectors.";
RL   Front. Biosci. 10:1106-1117(2005).
CC   -!- FUNCTION: Modulates viral and host transcriptional activity to promote
CC       viral genome replication. Stimulates viral E2a promoter activity by
CC       binding and inducing dimerization of host E2F. During viral infection
CC       E1A protein binds to cellular retinablastoma (RB) family members and
CC       dissociates these repressors from a complex with E2F proteins. Free E2F
CC       is then bound to E4orf6/7 which leads to transactivation of viral E2
CC       promoter, and cellular promoters such as E2F-1 promoter. Activation of
CC       cellular E2F targets promote cell cycle S phase and thereby possibly
CC       favorises viral DNA replication process. {ECO:0000269|PubMed:10666238,
CC       ECO:0000269|PubMed:8289811}.
CC   -!- SUBUNIT: Interacts with host E2F proteins. {ECO:0000269|PubMed:1832724,
CC       ECO:0000269|PubMed:2532611}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:15681431}.
CC   -!- SIMILARITY: Belongs to the adenoviridae E4-orf6/7 family.
CC       {ECO:0000305}.
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DR   EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A03804; Q4ADB2.
DR   RefSeq; AP_000191.1; AC_000007.1.
DR   Proteomes; UP000008167; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0019083; P:viral transcription; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Early protein; Host nucleus; Reference proteome; Transcription;
KW   Transcription regulation; Viral transcription.
FT   CHAIN           1..150
FT                   /note="Early 4 ORF6/7 control protein"
FT                   /id="PRO_0000036489"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           1..58
FT                   /note="Nuclear localization signal"
SQ   SEQUENCE   150 AA;  17054 MW;  D72D54018AD9DDB5 CRC64;
     MTTSGVPFGM TLRPTRSRLS RRTPYSRDRL PPFETETRAT ILEDHPLLPE CNTLTMHNAW
     TSPSPPVEQP QVGQQPVAQQ LDSDMNLSEL PGEFINITDE RLARQETVWN ITPKNMSVTH
     DMMLFKASRG ERTVYSVCWE GGGRLNTRVL