E434_ADE02
ID E434_ADE02 Reviewed; 294 AA.
AC P03239;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 65.
DE RecName: Full=Early 4 ORF6 protein;
DE Short=E4-ORF6;
DE AltName: Full=Early 4 34 kDa protein;
DE Short=E4-34k;
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 E1B-55K.
RX PubMed=6699935; DOI=10.1128/jvi.49.3.692-700.1984;
RA Sarnow P., Hearing P., Anderson C.W., Halbert D.N., Shenk T., Levine A.J.;
RT "Adenovirus early region 1B 58,000-dalton tumor antigen is physically
RT associated with an early region 4 25,000-dalton protein in productively
RT infected cells.";
RL J. Virol. 49:692-700(1984).
RN [3]
RP SUBCELLULAR LOCATION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=10233919; DOI=10.1128/jvi.73.6.4600-4610.1999;
RA Orlando J.S., Ornelles D.A.;
RT "An arginine-faced amphipathic alpha helix is required for adenovirus type
RT 5 e4orf6 protein function.";
RL J. Virol. 73:4600-4610(1999).
RN [4]
RP SUBCELLULAR LOCATION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=10211970; DOI=10.1099/0022-1317-80-4-997;
RA Leppard K.N., Everett R.D.;
RT "The adenovirus type 5 E1b 55K and E4 Orf3 proteins associate in infected
RT cells and affect ND10 components.";
RL J. Gen. Virol. 80:997-1008(1999).
RN [5]
RP ZINC-BINDING.
RX PubMed=10747932; DOI=10.1074/jbc.m000566200;
RA Boyer J.L., Ketner G.;
RT "Genetic analysis of a potential zinc-binding domain of the adenovirus E4
RT 34k protein.";
RL J. Biol. Chem. 275:14969-14978(2000).
RN [6]
RP INTERACTION WITH E1B-55K, AND MUTAGENESIS OF 243-ARG--LEU-245.
RX PubMed=11070042; DOI=10.1128/jvi.74.23.11407-11412.2000;
RA Cathomen T., Weitzman M.D.;
RT "A functional complex of adenovirus proteins E1B-55kDa and E4orf6 is
RT necessary to modulate the expression level of p53 but not its
RT transcriptional activity.";
RL J. Virol. 74:11407-11412(2000).
RN [7]
RP FUNCTION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=20484509; DOI=10.1128/jvi.00074-10;
RA Schreiner S., Wimmer P., Sirma H., Everett R.D., Blanchette P., Groitl P.,
RA Dobner T.;
RT "Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in
RT human adenovirus-infected cells.";
RL J. Virol. 84:7029-7038(2010).
RN [8]
RP FUNCTION.
RX PubMed=21123383; DOI=10.1128/jvi.02134-10;
RA Orazio N.I., Naeger C.M., Karlseder J., Weitzman M.D.;
RT "The adenovirus E1b55K/E4orf6 complex induces degradation of the Bloom
RT helicase during infection.";
RL J. Virol. 85:1887-1892(2011).
RN [9]
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: Plays a major role to prevent cellular inhibition of viral
CC genome replication by nuclear bodies. Assembles an SCF-like E3
CC ubiquitin ligase complex based on the cellular proteins ELOB, ELOC,
CC CUL5 and RBX1, in cooperation with viral E1B-55K. This viral RING-type
CC ligase ubiquitinates cellular substrates prior to proteasomal
CC degradation: p53/TP53, LIG4, MRE11-RAD50-NBS1 (MRN) complex, ITGA3,
CC DAXX and BLM. {ECO:0000269|PubMed:20484509,
CC ECO:0000269|PubMed:21123383}.
CC -!- SUBUNIT: Interacts with E1B-55k. {ECO:0000269|PubMed:11070042,
CC ECO:0000269|PubMed:6699935}.
CC -!- SUBCELLULAR LOCATION: Host nucleus. Host cytoplasm. Note=Colocalizes
CC with host PML-associated nuclear bodies.
CC -!- SIMILARITY: Belongs to the adenoviridae E4 30 to 34 kDa protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J01917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A03805; Q4ADC2.
DR RefSeq; AP_000192.1; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR007615; Adenovirus_E4_30/34.
DR Pfam; PF04528; Adeno_E4_34; 1.
PE 1: Evidence at protein level;
KW Early protein; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Metal-binding;
KW Modulation of host ubiquitin pathway by viral E3 ligase;
KW Modulation of host ubiquitin pathway by virus; Reference proteome;
KW Ubl conjugation pathway; Viral immunoevasion; Zinc.
FT CHAIN 1..294
FT /note="Early 4 ORF6 protein"
FT /id="PRO_0000221776"
FT MOTIF 239..255
FT /note="Nuclear localization signal"
FT MUTAGEN 243..245
FT /note="RRL->ARA: Complete loss of interaction with E1B-
FT 55k."
FT /evidence="ECO:0000269|PubMed:11070042"
SQ SEQUENCE 294 AA; 34116 MW; F60C83A38240BE0C CRC64;
MTTSGVPFGM TLRPTRSRLS RRTPYSRDRL PPFETETRAT ILEDHPLLPE CNTLTMHNVS
YVRGLPCSVG FTLIQEWVVP WDMVLTREEL VILRKCMHVC LCCANIDIMT SMMIHGYESW
ALHCHCSSPG SLQCIAGGQV LASWFRMVVD GAMFNQRFIW YREVVNYNMP KEVMFMSSVF
MRGRHLIYLR LWYDGHVGSV VPAMSFGYSA LHCGILNNIV VLCCSYCADL SEIRVRCCAR
RTRRLMLRAV RIIAEETTAM LYSCRTERRR QQFIRALLQH HRPILMHDYD STPM
