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E3RDB_ADE02
ID   E3RDB_ADE02             Reviewed;         130 AA.
AC   P03250;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-DEC-2020, entry version 78.
DE   RecName: Full=Early 3 receptor internalization and degradation beta protein;
DE            Short=E3 RID-beta protein;
DE   AltName: Full=Early E3B 14.5 kDa protein;
DE            Short=E3-14.5k;
DE   Flags: Precursor;
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=2309441; DOI=10.1016/0042-6822(90)90182-q;
RA   Tollefson A.E., Krajcsi P., Pursley M.H., Gooding L.R., Wold W.S.M.;
RT   "A 14,500 MW protein is coded by region E3 of group C human adenoviruses.";
RL   Virology 175:19-29(1990).
RN   [3]
RP   PHOSPHORYLATION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=1532104; DOI=10.1016/0042-6822(92)90451-t;
RA   Krajcsi P., Wold W.S.M.;
RT   "The adenovirus E3-14.5K protein which is required for prevention of TNF
RT   cytolysis and for down-regulation of the EGF receptor contains
RT   phosphoserine.";
RL   Virology 187:492-498(1992).
RN   [4]
RP   GLYCOSYLATION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=1533979; DOI=10.1016/0042-6822(92)90511-m;
RA   Krajcsi P., Tollefson A.E., Wold W.S.M.;
RT   "The E3-14.5K integral membrane protein of adenovirus that is required for
RT   down-regulation of the EGF receptor and for prevention of TNF cytolysis is
RT   O-glycosylated but not N-glycosylated.";
RL   Virology 188:570-579(1992).
RN   [5]
RP   TOPOLOGY.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=1531370; DOI=10.1128/jvi.66.3.1665-1673.1992;
RA   Krajcsi P., Tollefson A.E., Anderson C.W., Wold W.S.M.;
RT   "The adenovirus E3 14.5-kilodalton protein, which is required for down-
RT   regulation of the epidermal growth factor receptor and prevention of tumor
RT   necrosis factor cytolysis, is an integral membrane protein oriented with
RT   its C-terminus in the cytoplasm.";
RL   J. Virol. 66:1665-1673(1992).
RN   [6]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=7983708; DOI=10.1128/jvi.69.1.172-181.1995;
RA   Stewart A.R., Tollefson A.E., Krajcsi P., Yei S.P., Wold W.S.;
RT   "The adenovirus E3 10.4K and 14.5K proteins, which function to prevent
RT   cytolysis by tumor necrosis factor and to down-regulate the epidermal
RT   growth factor receptor, are localized in the plasma membrane.";
RL   J. Virol. 69:172-181(1995).
RN   [7]
RP   TYROSINE-BASED SORTING MOTIF.
RC   STRAIN=Human adenovirus C serotype 5;
RX   PubMed=12388693; DOI=10.1128/jvi.76.22.11329-11342.2002;
RA   Lichtenstein D.L., Krajcsi P., Esteban D.J., Tollefson A.E., Wold W.S.;
RT   "Adenovirus RIDbeta subunit contains a tyrosine residue that is critical
RT   for RID-mediated receptor internalization and inhibition of Fas- and TRAIL-
RT   induced apoptosis.";
RL   J. Virol. 76:11329-11342(2002).
RN   [8]
RP   REVIEW.
RX   PubMed=14690856; DOI=10.1080/08830180490265556;
RA   Lichtenstein D.L., Toth K., Doronin K., Tollefson A.E., Wold W.S.;
RT   "Functions and mechanisms of action of the adenovirus E3 proteins.";
RL   Int. Rev. Immunol. 23:75-111(2004).
RN   [9]
RP   REVIEW.
RX   PubMed=14674598; DOI=10.1007/978-3-662-05599-1_2;
RA   Windheim M., Hilgendorf A., Burgert H.G.;
RT   "Immune evasion by adenovirus E3 proteins: exploitation of intracellular
RT   trafficking pathways.";
RL   Curr. Top. Microbiol. Immunol. 273:29-85(2004).
CC   -!- FUNCTION: Prevents infected cell apoptosis induced by the host immune
CC       system. Acts by down-regulating a number of cell surface receptors in
CC       the tumor necrosis factor (TNF) receptor superfamily, namely FAS,
CC       TNFRSF10A/TRAIL receptor 1, and TNFRSF10B/TRAIL receptor 2. Down-
CC       regulation of these death receptors protects adenovirus-infected cells
CC       from apoptosis induced by the death receptor ligands Fas ligand and
CC       TRAIL. RID complex also down-regulates certain tyrosine kinase cell
CC       surface receptors, especially the epidermal growth factor receptor
CC       (EGFR). RID-mediated Fas and EGFR down-regulation occurs via
CC       endocytosis of the receptors into endosomes followed by transport to
CC       and degradation within lysosomes.
CC   -!- SUBUNIT: Interacts with E3 RID-alpha and E3 CR1-alpha.
CC   -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000269|PubMed:7983708};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:7983708}.
CC   -!- PTM: Phosphorylated on serine. {ECO:0000269|PubMed:1532104}.
CC   -!- PTM: O-glycosylated, but not N-glycosylated.
CC       {ECO:0000269|PubMed:1533979}.
CC   -!- SIMILARITY: Belongs to the adenoviridae E3_RID-beta family.
CC       {ECO:0000305}.
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DR   EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A03820; ERAD52.
DR   RefSeq; AP_000187.1; AC_000007.1.
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   GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR   InterPro; IPR008131; Adeno_E3_14_5.
DR   Pfam; PF04834; Adeno_E3_14_5; 1.
PE   1: Evidence at protein level;
KW   Early protein; Glycoprotein; Host membrane; Membrane; Phosphoprotein;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..130
FT                   /note="Early 3 receptor internalization and degradation
FT                   beta protein"
FT                   /id="PRO_0000036476"
FT   TRANSMEM        53..77
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          122..125
FT                   /note="Tyrosine-based sorting motif"
SQ   SEQUENCE   130 AA;  14529 MW;  4FADC90F04ABE5D1 CRC64;
     MKRSVIFVLL IFCALPVLCS QTSAPPKRHI SCRFTQIWNI PSCYNKQSDL SEAWLYAIIS
     VMVFCSTIFA LAIYPYLDIG WNAIDAMNHP TFPVPAVIPL QQVIAPINQP RPPSPTPTEI
     SYFNLTGGDD
 
 
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