VE2_BPV1
ID VE2_BPV1 Reviewed; 410 AA.
AC P03122; Q9WMH0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 23-FEB-2022, entry version 161.
DE RecName: Full=Regulatory protein E2 {ECO:0000255|HAMAP-Rule:MF_04001};
GN Name=E2 {ECO:0000255|HAMAP-Rule:MF_04001};
OS Bovine papillomavirus type 1.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Deltapapillomavirus.
OX NCBI_TaxID=337052;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6289124; DOI=10.1038/299529a0;
RA Chen E.Y., Howley P.M., Levinson A.D., Seeburg P.H.;
RT "The primary structure and genetic organization of the bovine
RT papillomavirus type 1 genome.";
RL Nature 299:529-534(1982).
RN [2]
RP DNA-BINDING REGION.
RX PubMed=2835232; DOI=10.1002/j.1460-2075.1988.tb02842.x;
RA McBride A.A., Schlegel R., Howley P.M.;
RT "The carboxy-terminal domain shared by the bovine papillomavirus E2
RT transactivator and repressor proteins contains a specific DNA binding
RT activity.";
RL EMBO J. 7:533-539(1988).
RN [3]
RP PHOSPHORYLATION AT SER-298 AND SER-301.
RX PubMed=2555544; DOI=10.1128/jvi.63.12.5076-5085.1989;
RA McBride A.A., Bolen J.B., Howley P.M.;
RT "Phosphorylation sites of the E2 transcriptional regulatory proteins of
RT bovine papillomavirus type 1.";
RL J. Virol. 63:5076-5085(1989).
RN [4]
RP REQUIREMENT FOR REPLICATION.
RX PubMed=1846806; DOI=10.1002/j.1460-2075.1991.tb07967.x;
RA Ustav M., Stenlung A.;
RT "Transient replication of BPV-1 requires two viral polypeptides encoded by
RT the E1 and E2 open reading frames.";
RL EMBO J. 10:449-457(1991).
RN [5]
RP REDOX REGULATION, AND MUTAGENESIS OF CYS-340.
RX PubMed=1323841; DOI=10.1073/pnas.89.16.7531;
RA McBride A.A., Klausner R.D., Howley P.M.;
RT "Conserved cysteine residue in the DNA-binding domain of the bovine
RT papillomavirus type 1 E2 protein confers redox regulation of the DNA-
RT binding activity in vitro.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7531-7535(1992).
RN [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH DDX11 AND BRD4, AND MUTAGENESIS OF
RP TRP-130.
RX PubMed=17189189; DOI=10.1016/j.molcel.2006.11.005;
RA Parish J.L., Bean A.M., Park R.B., Androphy E.J.;
RT "ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes
RT and viral genome maintenance.";
RL Mol. Cell 24:867-876(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 326-410.
RX PubMed=1328886; DOI=10.1038/359505a0;
RA Hegde R.S., Grossman S.R., Laimins L.A., Sigler P.B.;
RT "Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DNA-binding
RT domain bound to its DNA target.";
RL Nature 359:505-512(1992).
CC -!- FUNCTION: Plays a role in the initiation of viral DNA replication. A
CC dimer of E2 interacts with a dimer of E1 in order to improve
CC specificity of E1 DNA binding activity. Once the complex recognizes and
CC binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also
CC regulates viral transcription through binding to the E2RE response
CC element (5'-ACCNNNNNNGGT-3') present in multiple copies in the
CC regulatory regions of the viral genome. Activates or represses
CC transcription depending on E2RE's position with regards to proximal
CC promoter elements including the TATA-box. Repression occurs by
CC sterically hindering the assembly of the transcription initiation
CC complex. {ECO:0000255|HAMAP-Rule:MF_04001}.
CC -!- ACTIVITY REGULATION: Inactivated by oxidation of Cys-340 to a sulfenic
CC acid.
CC -!- SUBUNIT: Binds DNA as homodimer. Interacts with protein E1; this
CC interaction greatly increases E1 DNA-binding activity. Interacts with
CC protein L1; this interaction enhances E2-dependent replication and
CC transcription activation. Interacts with protein L2; this interaction
CC inhibits E2 transcriptional activity but not DNA replication function
CC E2. Interacts with protein E7; this interaction inhibits E7 oncogenic
CC activity. Interacts with host TAF1; this interaction modulates E2-
CC dependent transcriptional regulation. Interacts with host BRD4; this
CC interaction mediates E2 transcriptional activation function.
CC Additionally, the interaction with host BRD4 on mitotic chromosomes
CC mediates tethering of the viral genome. Interacts with host TOPBP1;
CC this interaction is required for optimal viral DNA replication.
CC Interacts with human DDX11. {ECO:0000255|HAMAP-Rule:MF_04001,
CC ECO:0000269|PubMed:17189189}.
CC -!- INTERACTION:
CC P03122; O60885-1: BRD4; Xeno; NbExp=2; IntAct=EBI-7028618, EBI-9345088;
CC P03122; P49715: CEBPA; Xeno; NbExp=2; IntAct=EBI-7028618, EBI-1172054;
CC P03122; P17676: CEBPB; Xeno; NbExp=3; IntAct=EBI-7028618, EBI-969696;
CC P03122; Q09472: EP300; Xeno; NbExp=3; IntAct=EBI-7028618, EBI-447295;
CC P03122; P41229: KDM5C; Xeno; NbExp=2; IntAct=EBI-7028618, EBI-1246541;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04001,
CC ECO:0000269|PubMed:17189189}. Note=Colocalizes with DDX11 at early
CC stages of mitosis.
CC -!- PTM: Oxidation of Cys-340 in response to redox signaling leads to the
CC loss of DNA-binding activity and the inactivation of gene activator or
CC repressor function. {ECO:0000269|PubMed:1323841}.
CC -!- PTM: Phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04001}.
CC -!- SIMILARITY: Belongs to the papillomaviridae E2 protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04001}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB46512.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X02346; CAB46512.1; ALT_FRAME; Genomic_DNA.
DR PIR; A03672; W2WLEB.
DR RefSeq; NP_056740.1; NC_001522.1.
DR PDB; 1DBD; NMR; -; A/B=311-410.
DR PDB; 1JJH; X-ray; 2.50 A; A/B/C=326-410.
DR PDB; 2BOP; X-ray; 1.70 A; A=326-410.
DR PDB; 2JEU; X-ray; 2.80 A; A=1-209.
DR PDB; 2JEX; X-ray; 2.35 A; A=1-209.
DR PDB; 6BUS; X-ray; 1.90 A; 1/2/3/4=310-410.
DR PDBsum; 1DBD; -.
DR PDBsum; 1JJH; -.
DR PDBsum; 2BOP; -.
DR PDBsum; 2JEU; -.
DR PDBsum; 2JEX; -.
DR PDBsum; 6BUS; -.
DR BMRB; P03122; -.
DR SMR; P03122; -.
DR DIP; DIP-40866N; -.
DR IntAct; P03122; 8.
DR MINT; P03122; -.
DR iPTMnet; P03122; -.
DR DNASU; 1489020; -.
DR GeneID; 1489020; -.
DR KEGG; vg:1489020; -.
DR EvolutionaryTrace; P03122; -.
DR Proteomes; UP000006567; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006275; P:regulation of DNA replication; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0039693; P:viral DNA genome replication; IDA:UniProtKB.
DR Gene3D; 1.10.287.30; -; 1.
DR Gene3D; 2.170.200.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR HAMAP; MF_04001; PPV_E2; 1.
DR InterPro; IPR035975; E2/EBNA1_C_sf.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR000427; Papillomavirus_E2_C.
DR InterPro; IPR001866; Papillomavirus_E2_N.
DR InterPro; IPR033668; Reg_prot_E2.
DR InterPro; IPR036050; Regulatory_protein_E2_N.
DR InterPro; IPR042503; Regulatory_protein_E2_N_1.
DR InterPro; IPR042504; Regulatory_protein_E2_N_2.
DR Pfam; PF00511; PPV_E2_C; 1.
DR Pfam; PF00508; PPV_E2_N; 1.
DR SUPFAM; SSF51332; SSF51332; 1.
DR SUPFAM; SSF54957; SSF54957; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA replication; DNA-binding; Early protein;
KW Host nucleus; Oxidation; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..410
FT /note="Regulatory protein E2"
FT /id="PRO_0000133172"
FT REGION 1..202
FT /note="Transactivation domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT REGION 198..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 325..410
FT /note="DNA-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001,
FT ECO:0000269|PubMed:2835232"
FT MOD_RES 298
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2555544"
FT MOD_RES 301
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2555544"
FT MUTAGEN 130
FT /note="W->R: Loss of ability to bind to DDX11, no effect on
FT ability to bind BRD4, loss of attachment to mitotic
FT chromosomes, and interference with the maintenance of
FT replicating viral episomes."
FT /evidence="ECO:0000269|PubMed:17189189"
FT MUTAGEN 340
FT /note="C->A: 90% decrease in DNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:1323841"
FT MUTAGEN 340
FT /note="C->G: <50% decrease in DNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:1323841"
FT MUTAGEN 340
FT /note="C->S: 50% decrease in DNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:1323841"
FT HELIX 4..21
FT /evidence="ECO:0007829|PDB:2JEX"
FT HELIX 26..48
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2JEX"
FT HELIX 62..83
FT /evidence="ECO:0007829|PDB:2JEX"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:2JEX"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:2JEX"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 104..120
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 127..140
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 142..152
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:2JEX"
FT TURN 162..165
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:2JEX"
FT HELIX 173..180
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:2JEX"
FT STRAND 327..333
FT /evidence="ECO:0007829|PDB:2BOP"
FT HELIX 335..348
FT /evidence="ECO:0007829|PDB:2BOP"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:2BOP"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:2BOP"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:2BOP"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:6BUS"
FT STRAND 370..382
FT /evidence="ECO:0007829|PDB:2BOP"
FT HELIX 383..392
FT /evidence="ECO:0007829|PDB:2BOP"
FT STRAND 400..405
FT /evidence="ECO:0007829|PDB:2BOP"
SQ SEQUENCE 410 AA; 45450 MW; F45B0BB74E679045 CRC64;
METACERLHV AQETQMQLIE KSSDKLQDHI LYWTAVRTEN TLLYAARKKG VTVLGHCRVP
HSVVCQERAK QAIEMQLSLQ ELSKTEFGDE PWSLLDTSWD RYMSEPKRCF KKGARVVEVE
FDGNASNTNW YTVYSNLYMR TEDGWQLAKA GADGTGLYYC TMAGAGRIYY SRFGDEAARF
STTGHYSVRD QDRVYAGVSS TSSDFRDRPD GVWVASEGPE GDPAGKEAEP AQPVSSLLGS
PACGPIRAGL GWVRDGPRSH PYNFPAGSGG SILRSSSTPV QGTVPVDLAS RQEEEEQSPD
STEEEPVTLP RRTTNDGFHL LKAGGSCFAL ISGTANQVKC YRFRVKKNHR HRYENCTTTW
FTVADNGAER QGQAQILITF GSPSQRQDFL KHVPLPPGMN ISGFTASLDF
