E3RDA_ADE02
ID E3RDA_ADE02 Reviewed; 91 AA.
AC P15133;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Pre-early 3 receptor internalization and degradation alpha protein;
DE Short=Pre-E3-RID-alpha protein;
DE Contains:
DE RecName: Full=Early 3 receptor internalization and degradation alpha protein;
DE Short=E3-RID-alpha protein;
DE AltName: Full=Pre-Early E3B 10.4 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=6253880; DOI=10.1093/nar/8.10.2173;
RA Herisse J., Courtois G., Galibert F.;
RT "Nucleotide sequence of the EcoRI D fragment of adenovirus 2 genome.";
RL Nucleic Acids Res. 8:2173-2192(1980).
RN [2]
RP SUBUNIT, AND MUTAGENESIS OF CYS-31.
RX PubMed=1377684; DOI=10.1016/s0021-9258(18)42237-5;
RA Hoffman P., Yaffe M.B., Hoffman B.L., Yei S., Wold W.S., Carlin C.;
RT "Characterization of the adenovirus E3 protein that down-regulates the
RT epidermal growth factor receptor. Evidence for intermolecular disulfide
RT bonding and plasma membrane localization.";
RL J. Biol. Chem. 267:13480-13487(1992).
RN [3]
RP SIGNAL SEQUENCE CLEAVAGE SITE, AND ALTERNATIVE PROCESSING.
RX PubMed=1531278; DOI=10.1016/0042-6822(92)90302-6;
RA Krajsci P., Tollefson A.E., Anderson C.W., Stewart A.R., Carlin C.R.,
RA Wold W.S.M.;
RT "The E3-10.4K protein of adenovirus is an integral membrane protein that is
RT partially cleaved between Ala22 and Ala23 and has a Ccyt orientation.";
RL Virology 187:131-144(1992).
RN [4]
RP FUNCTION.
RX PubMed=16227281; DOI=10.1128/jvi.79.21.13606-13617.2005;
RA Chin Y.R., Horwitz M.S.;
RT "Mechanism for removal of tumor necrosis factor receptor 1 from the cell
RT surface by the adenovirus RIDalpha/beta complex.";
RL J. Virol. 79:13606-13617(2005).
RN [5]
RP FUNCTION.
RX PubMed=18039930; DOI=10.1083/jcb.200702187;
RA Shah A.H., Cianciola N.L., Mills J.L., Sonnichsen F.D., Carlin C.;
RT "Adenovirus RIDalpha regulates endosome maturation by mimicking GTP-Rab7.";
RL J. Cell Biol. 179:965-980(2007).
RN [6]
RP FUNCTION.
RX PubMed=19948501; DOI=10.1083/jcb.200903039;
RA Cianciola N.L., Carlin C.R.;
RT "Adenovirus RID-alpha activates an autonomous cholesterol regulatory
RT mechanism that rescues defects linked to Niemann-Pick disease type C.";
RL J. Cell Biol. 187:537-552(2009).
RN [7]
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 [8]
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. {ECO:0000269|PubMed:16227281,
CC ECO:0000269|PubMed:18039930, ECO:0000269|PubMed:19948501}.
CC -!- SUBUNIT: Homodimer with only one chain cleaved by signal peptidase.
CC Interacts with E3 RID-beta and E3 CR1-alpha.
CC {ECO:0000269|PubMed:1377684}.
CC -!- SUBCELLULAR LOCATION: [Pre-early 3 receptor internalization and
CC degradation alpha protein]: Host membrane; Multi-pass membrane protein.
CC Host endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [Early 3 receptor internalization and degradation
CC alpha protein]: Host membrane; Single-pass type I membrane protein.
CC Host endoplasmic reticulum.
CC -!- PTM: The signal peptide is only cleaved partially by host signal
CC peptidase. This results in two forms of the protein, one uncleaved with
CC two transmembrane regions, and one cleaved with one transmembrane
CC region (PubMed:1531278). {ECO:0000269|PubMed:1531278}.
CC -!- SIMILARITY: Belongs to the adenoviridae E3-RID-alpha family.
CC {ECO:0000305}.
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DR EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; AP_000186.1; AC_000007.1.
DR SMR; P15133; -.
DR Proteomes; UP000008167; Genome.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR InterPro; IPR005041; Adeno_E3B.
DR Pfam; PF03376; Adeno_E3B; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Early protein; Host endoplasmic reticulum; Host membrane;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..91
FT /note="Pre-early 3 receptor internalization and degradation
FT alpha protein"
FT /id="PRO_0000421689"
FT PROPEP 1..22
FT /note="Signal peptide"
FT /id="PRO_0000421690"
FT CHAIN 23..91
FT /note="Early 3 receptor internalization and degradation
FT alpha protein"
FT /id="PRO_0000036470"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Name=TM1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..34
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 22..23
FT /note="Cleavage; by host signal peptidase"
FT DISULFID 31
FT /note="Interchain (with C-31 in Early 3 receptor
FT internalization and degradation alpha protein)"
FT MUTAGEN 31
FT /note="C->S: Complete loss of disulfide bonding."
FT /evidence="ECO:0000269|PubMed:1377684"
SQ SEQUENCE 91 AA; 10375 MW; 9328F70C6BBCE9EE CRC64;
MIPRVLILLT LVALFCACST LAAVAHIEVD CIPPFTVYLL YGFVTLILIC SLVTVVIAFI
QFIDWVCVRI AYLRHHPQYR DRTIADLLRI L
