ID   E3145_ADE02             Reviewed;         128 AA.
AC   P68976; P03249;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   23-FEB-2022, entry version 48.
DE   RecName: Full=Early 3 14.7 kDa protein;
DE            Short=E3-14.7k;
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=6262722; DOI=10.1093/nar/9.5.1229;
RA   Herisse J., Galibert F.;
RT   "Nucleotide sequence of the EcoRI E fragment of adenovirus 2 genome.";
RL   Nucleic Acids Res. 9:1229-1240(1981).
RN   [2]
RP   IDENTIFICATION OF PROTEIN.
RX   PubMed=2304142; DOI=10.1128/jvi.64.3.1250-1255.1990;
RA   Horton T.H., Tollefson A.E., Wold W.S.M., Gooding L.R.;
RT   "A protein serologically and functionally related to the group C E3 14,700-
RT   kilodalton protein is found in multiple adenovirus serotypes.";
RL   J. Virol. 64:1250-1255(1990).
RN   [3]
RP   INTERACTION WITH HOST RRAGA.
RX   PubMed=8995684; DOI=10.1128/jvi.71.2.1576-1582.1997;
RA   Li Y., Kang J., Horwitz M.S.;
RT   "Interaction of an adenovirus 14.7-kilodalton protein inhibitor of tumor
RT   necrosis factor alpha cytolysis with a new member of the GTPase superfamily
RT   of signal transducers.";
RL   J. Virol. 71:1576-1582(1997).
RN   [4]
RP   INTERACTION WITH HOST OPTN.
RX   PubMed=9488477; DOI=10.1128/mcb.18.3.1601;
RA   Li Y., Kang J., Horwitz M.S.;
RT   "Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor
RT   necrosis factor alpha-inducible cellular protein containing leucine zipper
RT   domains.";
RL   Mol. Cell. Biol. 18:1601-1610(1998).
RN   [5]
RP   INTERACTION WITH HOST IKBKG.
RX   PubMed=9927690; DOI=10.1073/pnas.96.3.1042;
RA   Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A.,
RA   Wallach D., Horwitz M.S.;
RT   "Identification of a cell protein (FIP-3) as a modulator of NF-kappaB
RT   activity and as a target of an adenovirus inhibitor of tumor necrosis
RT   factor alpha-induced apoptosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999).
RN   [6]
RP   CHARACTERIZATION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=11967368; DOI=10.1110/ps.4180102;
RA   Kim H.J., Foster M.P.;
RT   "Characterization of Ad5 E3-14.7K, an adenoviral inhibitor of apoptosis:
RT   structure, oligomeric state, and metal binding.";
RL   Protein Sci. 11:1117-1128(2002).
RN   [7]
RP   FUNCTION.
RX   PubMed=16423054; DOI=10.1111/j.1365-2567.2005.02277.x;
RA   Carmody R.J., Maguschak K., Chen Y.H.;
RT   "A novel mechanism of nuclear factor-kappaB regulation by adenoviral
RT   protein 14.7K.";
RL   Immunology 117:188-195(2006).
RN   [8]
RP   FUNCTION.
RX   PubMed=22675546; DOI=10.1371/journal.pone.0038348;
RA   Klingseisen L., Ehrenschwender M., Heigl U., Wajant H., Hehlgans T.,
RA   Schutze S., Schneider-Brachert W.;
RT   "E3-14.7K is recruited to TNF-receptor 1 and blocks TNF cytolysis
RT   independent from interaction with optineurin.";
RL   PLoS ONE 7:E38348-E38348(2012).
CC   -!- FUNCTION: May prevent Nf-kappaB activation by immune signals like Tumor
CC       necrosis factor, presumably by inhibiting NFKB1 dimer DNA-binding. May
CC       act directly at the TNF receptor to inhibit signaling.
CC       {ECO:0000269|PubMed:16423054, ECO:0000269|PubMed:22675546}.
CC   -!- SUBUNIT: May bind to host IKBKG, OPTN and RRAGA.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus.
CC   -!- SIMILARITY: Belongs to the adenoviridae E3_15 family. {ECO:0000305}.
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DR   EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A03818; ERAD42.
DR   RefSeq; AP_000188.1; AC_000007.1.
DR   Proteomes; UP000008167; 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:0039650; P:suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR   InterPro; IPR004985; Adeno_E3-15.
DR   Pfam; PF03307; Adeno_E3_15_3; 1.
PE   1: Evidence at protein level;
KW   Early protein; Host cytoplasm; Host nucleus; Host-virus interaction;
KW   Inhibition of host caspases by virus;
KW   Inhibition of host NF-kappa-B by virus;
KW   Modulation of host cell apoptosis by virus; Reference proteome.
FT   CHAIN           1..128
FT                   /note="Early 3 14.7 kDa protein"
FT                   /id="PRO_0000221745"
SQ   SEQUENCE   128 AA;  14738 MW;  09882D90B253F146 CRC64;
     MTESLDLELD GINTEQRLLE RRKAASERER LKQEVEDMVN LHQCKRGIFC VVKQAKLTYE
     KTTTGNRLSY KLPTQRQKLV LMVGEKPITV TQHSAETEGC LHFPYQGPED LCTLIKTMCG
     IRDLIPFN