VE2_HPV18
ID VE2_HPV18 Reviewed; 365 AA.
AC P06790;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 02-JUN-2021, entry version 152.
DE RecName: Full=Regulatory protein E2 {ECO:0000255|HAMAP-Rule:MF_04001};
GN Name=E2 {ECO:0000255|HAMAP-Rule:MF_04001};
OS Human papillomavirus type 18.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333761;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3039146; DOI=10.1016/0022-2836(87)90343-3;
RA Cole S.T., Danos O.;
RT "Nucleotide sequence and comparative analysis of the human papillomavirus
RT type 18 genome. Phylogeny of papillomaviruses and repeated structure of the
RT E6 and E7 gene products.";
RL J. Mol. Biol. 193:599-608(1987).
RN [2]
RP SEQUENCE REVISION TO 90.
RX PubMed=8383836; DOI=10.1093/nar/21.4.1041;
RA Meissner J.;
RT "TaqI is a single cut enzyme for HPV-18.";
RL Nucleic Acids Res. 21:1041-1041(1993).
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 P06790; O60885: BRD4; Xeno; NbExp=2; IntAct=EBI-7010629, EBI-723869;
CC P06790; P17676: CEBPB; Xeno; NbExp=4; IntAct=EBI-7010629, EBI-969696;
CC P06790; Q09472: EP300; Xeno; NbExp=6; IntAct=EBI-7010629, EBI-447295;
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X05015; CAA28667.1; ALT_SEQ; Genomic_DNA.
DR PIR; D26251; W2WL18.
DR PDB; 1F9F; X-ray; 1.90 A; A/B/C/D=287-365.
DR PDB; 1JJ4; X-ray; 2.40 A; A/B=287-365.
DR PDB; 1QQH; X-ray; 2.10 A; A=70-213.
DR PDB; 1TUE; X-ray; 2.10 A; B/E/G/J/L/Q=1-215.
DR PDBsum; 1F9F; -.
DR PDBsum; 1JJ4; -.
DR PDBsum; 1QQH; -.
DR PDBsum; 1TUE; -.
DR BMRB; P06790; -.
DR SMR; P06790; -.
DR IntAct; P06790; 57.
DR MINT; P06790; -.
DR EvolutionaryTrace; P06790; -.
DR Proteomes; UP000009109; Genome.
DR GO; GO:0044191; C:host cell mitochondrial membrane; IDA:CACAO.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044163; C:host cytoskeleton; IDA:CACAO.
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..365
FT /note="Regulatory protein E2"
FT /id="PRO_0000133197"
FT REGION 1..205
FT /note="Transactivation domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT REGION 286..365
FT /note="DNA-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT CROSSLNK 293
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001"
FT HELIX 4..25
FT /evidence="ECO:0007829|PDB:1TUE"
FT HELIX 30..52
FT /evidence="ECO:0007829|PDB:1TUE"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:1TUE"
FT HELIX 72..88
FT /evidence="ECO:0007829|PDB:1QQH"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:1QQH"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:1QQH"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 113..125
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 129..144
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:1TUE"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:1QQH"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:1QQH"
FT STRAND 287..295
FT /evidence="ECO:0007829|PDB:1F9F"
FT HELIX 296..309
FT /evidence="ECO:0007829|PDB:1F9F"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:1F9F"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:1F9F"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:1F9F"
FT HELIX 340..349
FT /evidence="ECO:0007829|PDB:1F9F"
FT STRAND 356..364
FT /evidence="ECO:0007829|PDB:1F9F"
SQ SEQUENCE 365 AA; 41294 MW; 7871AD816A457ACB CRC64;
MQTPKETLSE RLSCVQDKII DHYENDSKDI DSQIQYWQLI RWENAIFFAA REHGIQTLNH
QVVPAYNISK SKAHKAIELQ MALQGLAQSA YKTEDWTLQD TCEELWNTEP THCFKKGGQT
VQVYFDGNKD NCMTYVAWDS VYYMTDAGTW DKTATCVSHR GLYYVKEGYN TFYIEFKSEC
EKYGNTGTWE VHFGNNVIDC NDSMCSTSDD TVSATQLVKQ LQHTPSPYSS TVSVGTAKTY
GQTSAATRPG HCGLAEKQHC GPVNPLLGAA TPTGNNKRRK LCSGNTTPII HLKGDRNSLK
CLRYRLRKHS DHYRDISSTW HWTGAGNEKT GILTVTYHSE TQRTKFLNTV AIPDSVQILV
GYMTM
