ID   VE2_HPV28               Reviewed;         376 AA.
AC   P50771;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   03-AUG-2022, entry version 88.
DE   RecName: Full=Regulatory protein E2 {ECO:0000255|HAMAP-Rule:MF_04001};
GN   Name=E2 {ECO:0000255|HAMAP-Rule:MF_04001};
OS   Human papillomavirus 28.
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC   Alphapapillomavirus.
OX   NCBI_TaxID=37111;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Delius H.;
RL   Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
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   -!- 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; U31783; AAA79425.1; -; Genomic_DNA.
DR   SMR; P50771; -.
DR   PRIDE; P50771; -.
DR   Proteomes; UP000009158; 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   3: Inferred from homology;
KW   Activator; DNA replication; DNA-binding; Early protein; Host nucleus;
KW   Isopeptide bond; Phosphoprotein; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation.
FT   CHAIN           1..376
FT                   /note="Regulatory protein E2"
FT                   /id="PRO_0000133207"
FT   REGION          1..206
FT                   /note="Transactivation domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT   REGION          211..271
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          294..376
FT                   /note="DNA-binding domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT   COMPBIAS        218..271
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CROSSLNK        301
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
SQ   SEQUENCE   376 AA;  43234 MW;  7F16BFDB7E85DF79 CRC64;
     METLANRLDV CQDKMLELYE KDSNKLEDQI MHWQLMRVEN ALLYKARECG LTHIGHQVVP
     PLSVTKAKAR SAIEVHVALL QLQESAYAQD SWTLRDTSRE MWDTVPKKCW KKRGVTVEVR
     YDGDETKSMC YVHWRDIFTQ NYSDDKWVKV AGHVSYEGLY YIHEGEQTFY VKFKDDAYVY
     GETGKWEVHV GGKVIHHHAF DPVSSTREIP AAGPLCTGDT TKASTETSVG ATEGPQQKRQ
     RLETLNWEQQ QRQYPQTPST QTTERASQPL DVTRTSDCDT TCPYTVGHPS DPDCAPVVHL
     KGDPNCLKCF RYRLHKGKRK LYCKTSSTWR WSCESENQAA FVTIWYTSYS QRNEFLSTVK
     VPPGIQVILG HMSMFV