ID   E4RF1_ADE02             Reviewed;         128 AA.
AC   P03242;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2013, sequence version 2.
DT   23-FEB-2022, entry version 76.
DE   RecName: Full=Early 4 ORF1 protein;
DE            Short=E4-ORF1;
DE   AltName: Full=E4 ORF1 control 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], AND ALTERNATIVE SPLICING.
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   FUNCTION.
RX   PubMed=12569363; DOI=10.1038/sj.onc.1206151;
RA   Frese K.K., Lee S.S., Thomas D.L., Latorre I.J., Weiss R.S.,
RA   Glaunsinger B.A., Javier R.T.;
RT   "Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-
RT   kinase by the adenovirus E4-ORF1 oncoprotein.";
RL   Oncogene 22:710-721(2003).
RN   [3]
RP   FUNCTION.
RX   PubMed=15970698; DOI=10.4161/cc.4.7.1791;
RA   O'Shea C.C., Choi S., McCormick F., Stokoe D.;
RT   "Adenovirus overrides cellular checkpoints for protein translation.";
RL   Cell Cycle 4:883-888(2005).
RN   [4]
RP   INTERACTION WITH HOST PDZ-MOTIF PROTEINS.
RX   PubMed=17314165; DOI=10.1128/jvi.02855-06;
RA   Chung S.H., Frese K.K., Weiss R.S., Prasad B.V., Javier R.T.;
RT   "A new crucial protein interaction element that targets the adenovirus E4-
RT   ORF1 oncoprotein to membrane vesicles.";
RL   J. Virol. 81:4787-4797(2007).
RN   [5]
RP   INTERACTION WITH HOST DLG1; PATJ AND TJP2.
RX   PubMed=19029943; DOI=10.1038/onc.2008.352;
RA   Javier R.T.;
RT   "Cell polarity proteins: common targets for tumorigenic human viruses.";
RL   Oncogene 27:7031-7046(2008).
RN   [6]
RP   FUNCTION.
RX   PubMed=21775458; DOI=10.1128/jvi.05410-11;
RA   Javier R.T., Rice A.P.;
RT   "Emerging theme: cellular PDZ proteins as common targets of pathogenic
RT   viruses.";
RL   J. Virol. 85:11544-11556(2011).
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: May modulate tight-junctions functions of infected cells
CC       through interactions with PDZ proteins. E4 ORF1 has ben show for
CC       Adenovirus 9 to interact with protein involved in tight junction
CC       regulation. May play a role in mTOR activation by activating PI3-
CC       kinase, thus overriding cellular checkpoint for translation.
CC       {ECO:0000269|PubMed:12569363, ECO:0000269|PubMed:15970698,
CC       ECO:0000269|PubMed:21775458}.
CC   -!- SUBUNIT: May interact with host PDZ proteins through the PDZ domain
CC       binding motif (PBM), namely host DLG1, PATJ AND TJP2.
CC   -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the adenoviridae E4-ORF1 family. {ECO:0000305}.
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DR   EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A03808; Q4ADG2.
DR   RefSeq; AP_000196.1; AC_000007.1.
DR   SMR; P03242; -.
DR   Proteomes; UP000008167; Genome.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; 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; SSF51283; 1.
PE   1: Evidence at protein level;
KW   Early protein; Host membrane; Host-virus interaction; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..128
FT                   /note="Early 4 ORF1 protein"
FT                   /id="PRO_0000221785"
FT   TOPO_DOM        1..26
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        27..47
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        48..99
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        100..120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        121..128
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOTIF           125..128
FT                   /note="PBZ domain binding motif"
SQ   SEQUENCE   128 AA;  14277 MW;  5CC9ADE844F8C060 CRC64;
     MAAAVEALYV VLEREGAILP RQEGFSGVYV FFSPINFVIP PMGAVMLSLR LRVCIPPGYF
     GRFLALTDVN QPDVFTESYI MTPDMTEELS VVLFNHGDQF FYGHAGMAVV RLMLIRVVFP
     VVRQASNV