E4RF3_ADE02
ID E4RF3_ADE02 Reviewed; 116 AA.
AC P03241;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 29-SEP-2021, entry version 62.
DE RecName: Full=Early 4 ORF3 protein;
DE Short=E4-ORF3;
DE AltName: Full=E4 ORF3 control protein;
DE AltName: Full=Early 4 11 kDa protein;
DE Short=E4-11k;
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 FUNCTION.
RX PubMed=8264611; DOI=10.1128/mcb.14.1.437-445.1994;
RA Nordqvist K., Ohman K., Akusjarvi G.;
RT "Human adenovirus encodes two proteins which have opposite effects on
RT accumulation of alternatively spliced mRNAs.";
RL Mol. Cell. Biol. 14:437-445(1994).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=7559785; DOI=10.1083/jcb.131.1.45;
RA Carvalho T., Seeler J.S., Ohman K., Jordan P., Pettersson U., Akusjarvi G.,
RA Carmo-Fonseca M., Dejean A.;
RT "Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-
RT associated PML bodies.";
RL J. Cell Biol. 131:45-56(1995).
RN [4]
RP INTERACTION WITH E1B-55K PROTEIN.
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 INTERACTION WITH HOST MRE11/RAD50/NBS1.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=12124628; DOI=10.1038/nature00863;
RA Stracker T.H., Carson C.T., Weitzman M.D.;
RT "Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair
RT complex.";
RL Nature 418:348-352(2002).
RN [6]
RP INTERACTION WITH E1B-55K, CREBBP, EP300, AND PRKDC.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=12692231; DOI=10.1128/jvi.77.9.5295-5304.2003;
RA Evans J.D., Hearing P.;
RT "Distinct roles of the Adenovirus E4 ORF3 protein in viral DNA replication
RT and inhibition of genome concatenation.";
RL J. Virol. 77:5295-5304(2003).
RN [7]
RP MUTAGENESIS OF ASN-82; LEU-103 AND LEU-106.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=15858005; DOI=10.1128/jvi.79.10.6207-6215.2005;
RA Evans J.D., Hearing P.;
RT "Relocalization of the Mre11-Rad50-Nbs1 complex by the adenovirus E4 ORF3
RT protein is required for viral replication.";
RL J. Virol. 79:6207-6215(2005).
RN [8]
RP INTERACTION WITH HOST PML ISOFORM-2.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=16501113; DOI=10.1128/jvi.80.6.3042-3049.2006;
RA Hoppe A., Beech S.J., Dimmock J., Leppard K.N.;
RT "Interaction of the adenovirus type 5 E4 Orf3 protein with promyelocytic
RT leukemia protein isoform II is required for ND10 disruption.";
RL J. Virol. 80:3042-3049(2006).
RN [9]
RP INTERACTION WITH HOST TRIM24.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=17287283; DOI=10.1128/jvi.02629-06;
RA Yondola M.A., Hearing P.;
RT "The adenovirus E4 ORF3 protein binds and reorganizes the TRIM family
RT member transcriptional intermediary factor 1 alpha.";
RL J. Virol. 81:4264-4271(2007).
RN [10]
RP FUNCTION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=17301128; DOI=10.1128/jvi.02385-06;
RA Ullman A.J., Reich N.C., Hearing P.;
RT "Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral
RT response.";
RL J. Virol. 81:4744-4752(2007).
RN [11]
RP FUNCTION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=18480450; DOI=10.1128/jvi.00723-08;
RA Ullman A.J., Hearing P.;
RT "Cellular proteins PML and Daxx mediate an innate antiviral defense
RT antagonized by the adenovirus E4 ORF3 protein.";
RL J. Virol. 82:7325-7335(2008).
RN [12]
RP INTERACTION WITH HOST PML ISOFORM-2.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=19088278; DOI=10.1099/vir.0.005512-0;
RA Leppard K.N., Emmott E., Cortese M.S., Rich T.;
RT "Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML)
RT protein nuclear domains for disruption via a sequence in PML isoform II
RT that is predicted as a protein interaction site by bioinformatic
RT analysis.";
RL J. Gen. Virol. 90:95-104(2009).
RN [13]
RP FUNCTION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=21700307; DOI=10.1016/j.virol.2011.05.017;
RA Greer A.E., Hearing P., Ketner G.;
RT "The adenovirus E4 11 k protein binds and relocalizes the cytoplasmic P-
RT body component Ddx6 to aggresomes.";
RL Virology 417:161-168(2011).
RN [14]
RP INTERACTION WITH TRIM24.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=22123502; DOI=10.1016/j.virol.2011.10.033;
RA Vink E.I., Yondola M.A., Wu K., Hearing P.;
RT "Adenovirus E4-ORF3-dependent relocalization of TIF1alpha and TIF1gamma
RT relies on access to the Coiled-Coil motif.";
RL Virology 422:317-325(2012).
RN [15]
RP SUBUNIT.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=22573317; DOI=10.1074/jbc.m112.344234;
RA Patsalo V., Yondola M.A., Luan B., Shoshani I., Kisker C., Green D.F.,
RA Raleigh D.P., Hearing P.;
RT "Biophysical and functional analyses suggest that adenovirus E4-ORF3
RT protein requires higher-order multimerization to function against
RT promyelocytic leukemia protein nuclear bodies.";
RL J. Biol. Chem. 287:22573-22583(2012).
RN [16]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=23063122; DOI=10.1016/j.cell.2012.08.035;
RA Ou H.D., Kwiatkowski W., Deerinck T.J., Noske A., Blain K.Y., Land H.S.,
RA Soria C., Powers C.J., May A.P., Shu X., Tsien R.Y., Fitzpatrick J.A.,
RA Long J.A., Ellisman M.H., Choe S., O'Shea C.C.;
RT "A structural basis for the assembly and functions of a viral polymer that
RT inactivates multiple tumor suppressors.";
RL Cell 151:304-319(2012).
RN [17]
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: Forms a multivalent network in host nucleus that inhibits
CC nuclear bodies and prevents antiviral cellular activities. The network
CC is made of multimerized dimers and surrounds adenovirus replication
CC centers and nucleolus. Plays a role in splicing of the major late
CC transcript. Prevents viral genome concatemer formation.
CC {ECO:0000269|PubMed:17301128, ECO:0000269|PubMed:18480450,
CC ECO:0000269|PubMed:21700307, ECO:0000269|PubMed:8264611}.
CC -!- SUBUNIT: Homodimer. Multimerizes through C-terminus tail by reciprocal
CC or nonreciprocal interactions. Interacts with host PML isoform 2 C-
CC terminal disordered region. Interacts with E1B-55k; this interaction is
CC necessary for E1B 55 kDa protein to localize to the nuclear matrix
CC fraction of the cell (PubMed:10211970). May interact with host TRIM24,
CC CREBBP, EP300, PRKDC and the MRN complex MRE11/RAD50/NBS1; these
CC interactions may happen through nuclear bodies complexes.
CC {ECO:0000269|PubMed:10211970, ECO:0000269|PubMed:12124628,
CC ECO:0000269|PubMed:12692231, ECO:0000269|PubMed:16501113,
CC ECO:0000269|PubMed:17287283, ECO:0000269|PubMed:19088278,
CC ECO:0000269|PubMed:22123502, ECO:0000269|PubMed:22573317,
CC ECO:0000269|PubMed:23063122}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:23063122,
CC ECO:0000269|PubMed:7559785}. Note=forms networks in the nucleus that
CC may surround adenovirus replication centers.
CC -!- INDUCTION: Synthesized early during infection.
CC -!- SIMILARITY: Belongs to the adenoviridae E4 ORF3 family. {ECO:0000305}.
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DR EMBL; J01917; AAA92224.1; -; Genomic_DNA.
DR PIR; A03807; Q4ADE2.
DR RefSeq; AP_000194.1; AC_000007.1.
DR RefSeq; NP_040534.1; NC_001405.1.
DR SMR; P03241; -.
DR GeneID; 2652989; -.
DR Proteomes; UP000008167; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.2870; -; 1.
DR InterPro; IPR009699; Mastadenovirus_E4/Orf3.
DR InterPro; IPR038368; Mastadenovirus_E4/Orf3_sf.
DR Pfam; PF06931; Adeno_E4_ORF3; 1.
PE 1: Evidence at protein level;
KW Early protein; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Reference proteome;
KW Viral immunoevasion.
FT CHAIN 1..116
FT /note="Early 4 ORF3 protein"
FT /id="PRO_0000221770"
FT MUTAGEN 82
FT /note="N->A: Complete loss of virus replication."
FT /evidence="ECO:0000269|PubMed:15858005"
FT MUTAGEN 88..90
FT /note="LAV->AAA: No effect on viral DNA replication."
FT MUTAGEN 103
FT /note="L->A: Complete loss of virus replication."
FT /evidence="ECO:0000269|PubMed:15858005"
FT MUTAGEN 105..106
FT /note="DL->AA: Complete loss of viral DNA replication."
FT MUTAGEN 106
FT /note="L->A: Complete loss of virus replication."
FT /evidence="ECO:0000269|PubMed:15858005"
FT MUTAGEN 107..108
FT /note="HF->AA: Complete loss of viral DNA replication."
SQ SEQUENCE 116 AA; 13255 MW; B4E5F39A9F90EF1A CRC64;
MIRCLRLKVE GALEQIFTMA GLNIRDLLRD ILIRWRDENY LGMVEGAGMF IEEIHPEGFS
LYVHLDVRAV CLLEAIVQHL TNAIICSLAV EFDHATGGER VHLIDLHFEV LDNLLE
