ID   E1B55_ADE02             Reviewed;         495 AA.
AC   P03244; Q67789; Q67790;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 2.
DT   25-MAY-2022, entry version 90.
DE   RecName: Full=E1B 55 kDa protein;
DE            Short=E1B-55K;
DE   AltName: Full=E1B protein, large T-antigen;
DE   AltName: Full=E1B-495R;
GN   Name=E1B;
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=7142161; DOI=10.1016/s0021-9258(18)33473-2;
RA   Gingeras T.R., Sciaky D., Gelinas R.E., Bing-Dong J., Yen C.E., Kelly M.M.,
RA   Bullock P.A., Parsons B.L., O'Neill K.E., Roberts R.J.;
RT   "Nucleotide sequences from the adenovirus-2 genome.";
RL   J. Biol. Chem. 257:13475-13491(1982).
RN   [2]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH E4-ORF3 PROTEIN.
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   [3]
RP   INTERACTION WITH E4-ORF6.
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).
CC   -!- FUNCTION: Plays a major role to prevent cellular inhibition of viral
CC       genome replication. Assembles an SCF-like E3 ubiquitin ligase complex
CC       based on the cellular proteins ELOB, ELOC, CUL5 and RBX1, in
CC       cooperation with viral E4orf6. This viral RING-type ligase
CC       ubiquitinates cellular substrates and targets them to proteasomal
CC       degradation: TP53/p53, LIG4, MRE11-RAD50-NBS1 (MRN) complex, ITGA3,
CC       DAXX and BLM. Degradation of host TP53/p53 activity is essential for
CC       preventing E1A-induced TP53 accumulation that would otherwise lead to
CC       cell apoptosis and growth arrest. E1B-55K also inactivates TP53
CC       transcription-factor activity by binding its transactivation domain.
CC       E1B-55K also functions as a SUMO1 E3 ligase for TP53 which causes the
CC       latter to be sequestered in promyelocytic leukemia (PML) nuclear bodies
CC       thereby contributing to maximal inhibition of TP53 function.
CC       {ECO:0000250|UniProtKB:P03243}.
CC   -!- SUBUNIT: Interacts with the transactivation domain of TP53 (via N-
CC       terminus); this interaction leads to the inhibition of TP53 function
CC       and/or its degradation (By similarity). Interacts with host PML-4 and
CC       PML-5; this interaction promotes efficient subnuclear targeting of E1B-
CC       55K to PML nuclear bodies (By similarity). Interacts with E4-ORF3
CC       protein (PubMed:10211970). Interacts with E4-ORF6 protein
CC       (PubMed:11070042). Interacts with host DAXX protein; this interaction
CC       might alterate the normal interactions of DAXX, PML, and p53, which may
CC       contribute to cell transformation (By similarity).
CC       {ECO:0000250|UniProtKB:P03243, ECO:0000269|PubMed:10211970,
CC       ECO:0000269|PubMed:11070042}.
CC   -!- INTERACTION:
CC       P03244; Q9UER7: DAXX; Xeno; NbExp=4; IntAct=EBI-1561155, EBI-77321;
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:10211970}. Host
CC       cytoplasm {ECO:0000269|PubMed:10211970}. Note=Colocalizes with host
CC       TP53 to host PML nuclear bodies. PML localization of E1B-55K is
CC       necessary for E1B-55K-dependent SUMOylation of TP53.
CC       {ECO:0000250|UniProtKB:P03243}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC         Comment=At least five different polypeptides are generated by
CC         alternative splicing of a common mRNA precursor.;
CC       Name=E1B-495R; Synonyms=E1B-55K;
CC         IsoId=P03244-1; Sequence=Displayed;
CC       Name=E1B-155R; Synonyms=E1B-18K;
CC         IsoId=P03244-2; Sequence=Not described;
CC       Name=E1B-92R; Synonyms=E1B-16K;
CC         IsoId=P03244-3; Sequence=Not described;
CC       Name=E1B-82R; Synonyms=E1B-15K;
CC         IsoId=P03244-4; Sequence=Not described;
CC       Name=E1B-175R; Synonyms=E1B-19K;
CC         IsoId=P03247-1; Sequence=External;
CC   -!- DOMAIN: Contains a PML interaction motif that allows the subnuclear PML
CC       localization. {ECO:0000250|UniProtKB:P03243}.
CC   -!- SIMILARITY: Belongs to the adenoviridae E1B 55 kDa protein family.
CC       {ECO:0000305}.
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DR   EMBL; J01917; AAA92201.1; -; Genomic_DNA.
DR   EMBL; J01917; AAA92202.1; -; Genomic_DNA.
DR   EMBL; J01917; AAA92203.1; -; Genomic_DNA.
DR   PIR; B03809; Q1AD52.
DR   RefSeq; AP_000163.1; AC_000007.1. [P03244-1]
DR   RefSeq; NP_040511.1; NC_001405.1.
DR   SMR; P03244; -.
DR   IntAct; P03244; 3.
DR   MINT; P03244; -.
DR   GeneID; 2652981; -.
DR   KEGG; vg:2652981; -.
DR   Proteomes; UP000008167; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR   GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 2.160.20.10; -; 1.
DR   InterPro; IPR006717; Adeno_E1B_55K_N.
DR   InterPro; IPR002612; Adeno_E1B_55kDa.
DR   InterPro; IPR012334; Pectin_lyas_fold.
DR   InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR   Pfam; PF01696; Adeno_E1B_55K; 1.
DR   Pfam; PF04623; Adeno_E1B_55K_N; 1.
DR   SUPFAM; SSF51126; SSF51126; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Early protein; Host cytoplasm; Host nucleus;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host PKR by virus;
KW   Modulation of host cell apoptosis by virus; Reference proteome;
KW   Viral immunoevasion.
FT   CHAIN           1..495
FT                   /note="E1B 55 kDa protein"
FT                   /id="PRO_0000221724"
FT   REGION          1..74
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        21..37
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   495 AA;  54909 MW;  D6665B27183720CC CRC64;
     MERRNPSERG VPAGFSGHAS VESGGETQES PATVVFRPPG NNTDGGATAG GSQAAAAAGA
     EPMEPESRPG PSGMNVVQVA ELFPELRRIL TINEDGQGLK GVKRERGASE ATEEARNLTF
     SLMTRHRPEC VTFQQIKDNC ANELDLLAQK YSIEQLTTYW LQPGDDFEEA IRVYAKVALR
     PDCKYKISKL VNIRNCCYIS GNGAEVEIDT EDRVAFRCSM INMWPGVLGM DGVVIMNVRF
     TGPNFSGTVF LANTNLILHG VSFYGFNNTC VEAWTDVRVR GCAFYCCWKG VVCRPKSRAS
     IKKCLFERCT LGILSEGNSR VRHNVASDCG CFMLVKSVAV IKHNMVCGNC EDRASQMLTC
     SDGNCHLLKT IHVASHSRKA WPVFEHNILT RCSLHLGNRR GVFLPYQCNL SHTKILLEPE
     SMSKVNLNGV FDMTMKIWKV LRYDETRTRC RPCECGGKHI RNQPVMLDVT EELRPDHLVL
     ACTRAEFGSS DEDTD