ID   VE2_HPV31               Reviewed;         372 AA.
AC   P17383;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   02-JUN-2021, entry version 133.
DE   RecName: Full=Regulatory protein E2 {ECO:0000255|HAMAP-Rule:MF_04001};
GN   Name=E2 {ECO:0000255|HAMAP-Rule:MF_04001};
OS   Human papillomavirus 31.
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC   Alphapapillomavirus.
OX   NCBI_TaxID=10585;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2545036; DOI=10.1016/0042-6822(89)90545-x;
RA   Goldsborough M.D., Disilvestre D., Temple G.F., Lorincz A.T.;
RT   "Nucleotide sequence of human papillomavirus type 31: a cervical neoplasia-
RT   associated virus.";
RL   Virology 171:306-311(1989).
RN   [2]
RP   STRUCTURE BY NMR OF 291-372.
RX   PubMed=8652551; DOI=10.1021/bi951932w;
RA   Liang H., Petros A.M., Meadows R.P., Yoon H.S., Egan D.A., Walter K.,
RA   Holzman T.F., Robins T., Fesik S.W.;
RT   "Solution structure of the DNA-binding domain of a human papillomavirus E2
RT   protein: evidence for flexible DNA-binding regions.";
RL   Biochemistry 35:2095-2103(1996).
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   -!- 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       {ECO:0000255|HAMAP-Rule:MF_04001}.
CC   -!- INTERACTION:
CC       P17383; O60885: BRD4; Xeno; NbExp=2; IntAct=EBI-7010529, EBI-723869;
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04001}.
CC   -!- PTM: Phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04001}.
CC   -!- PTM: Sumoylation plays a regulatory role in E2 transcriptional
CC       activity. {ECO:0000255|HAMAP-Rule:MF_04001}.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E2 protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04001}.
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DR   EMBL; J04353; AAA46953.1; -; Genomic_DNA.
DR   PIR; D32444; W2WL31.
DR   PDB; 1A7G; X-ray; 2.40 A; E=291-372.
DR   PDB; 1DHM; NMR; -; A/B=291-372.
DR   PDBsum; 1A7G; -.
DR   PDBsum; 1DHM; -.
DR   BMRB; P17383; -.
DR   SMR; P17383; -.
DR   IntAct; P17383; 1.
DR   MINT; P17383; -.
DR   EvolutionaryTrace; P17383; -.
DR   Proteomes; UP000009116; 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; IEA:UniProtKB-UniRule.
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; Isopeptide bond; Phosphoprotein; Reference proteome;
KW   Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT   CHAIN           1..372
FT                   /note="Regulatory protein E2"
FT                   /id="PRO_0000133211"
FT   REGION          1..200
FT                   /note="Transactivation domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT   REGION          235..262
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          292..372
FT                   /note="DNA-binding domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT   COMPBIAS        240..262
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CROSSLNK        299
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT   STRAND          292..300
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   HELIX           302..311
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   HELIX           312..314
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   HELIX           316..318
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   STRAND          331..333
FT                   /evidence="ECO:0007829|PDB:1DHM"
FT   TURN            334..337
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   STRAND          338..343
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   HELIX           347..356
FT                   /evidence="ECO:0007829|PDB:1A7G"
FT   STRAND          363..371
FT                   /evidence="ECO:0007829|PDB:1A7G"
SQ   SEQUENCE   372 AA;  42104 MW;  4F387C5E3AFB9D1D CRC64;
     METLSQRLNV CQDKILEHYE NDSKRLCDHI DYWKHIRLEC VLMYKAREMG IHSINHQVVP
     ALSVSKAKAL QAIELQMMLE TLNNTEYKNE DWTMQQTSLE LYLTAPTGCL KKHGYTVEVQ
     FDGDVHNTMH YTNWKFIYLC IDGQCTVVEG QVNCKGIYYV HEGHITYFVN FTEEAKKYGT
     GKKWEVHAGG QVIVFPESVF SSDEISFAGI VTKLPTANNT TTSNSKTCAL GTSEGVRRAT
     TSTKRPRTEP EHRNTHHPNK LLRGDSVDSV NCGVISAAAC TNQTRAVSCP ATTPIIHLKG
     DANILKCLRY RLSKYKQLYE QVSSTWHWTC TDGKHKNAIV TLTYISTSQR DDFLNTVKIP
     NTVSVSTGYM TI