UniProt functional annotation for P03120

UniProt code: P03120.

Organism: Human papillomavirus type 16.
Taxonomy: Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes; Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae; Alphapapillomavirus.
 
Function: Plays a role in the initiation of viral DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex. {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:1326651, ECO:0000269|PubMed:15681049, ECO:0000269|PubMed:16611886, ECO:0000269|PubMed:25340539, ECO:0000269|PubMed:26365679, ECO:0000269|PubMed:3033289}.
 
Subunit: Binds DNA as homodimer. Interacts with protein E1; this interaction greatly increases E1 DNA-binding activity. Interacts with protein L1; this interaction enhances E2-dependent replication and transcription activation. Interacts with protein L2; this interaction inhibits E2 transcriptional activity but not DNA replication function E2. Interacts with protein E7; this interaction inhibits E7 oncogenic activity. Interacts with host TAF1; this interaction modulates E2- dependent transcriptional regulation. Interacts with host BRD4; this interaction mediates E2 transcriptional activation function. Additionally, the interaction with host BRD4 on mitotic chromosomes mediates tethering of the viral genome. Interacts with host TOPBP1; this interaction is required for optimal viral DNA replication. {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:15681049, ECO:0000269|PubMed:16439535, ECO:0000269|PubMed:16611886, ECO:0000269|PubMed:17189190, ECO:0000269|PubMed:18580066, ECO:0000269|PubMed:22973044, ECO:0000269|PubMed:25911730, ECO:0000269|PubMed:7645246, ECO:0000269|PubMed:9878365}.
Subcellular location: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:18619639, ECO:0000269|PubMed:25340539, ECO:0000269|PubMed:25911730, ECO:0000269|PubMed:7645246}.
Ptm: Phosphorylated. Phosphorylation at Ser-243 mediates binding to host Brd4 and is required for host chromosome binding. {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:25340539, ECO:0000269|PubMed:7645246}.
Ptm: Sumoylation plays a regulatory role in E2 transcriptional activity. {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:18619639}.
Miscellaneous: HPV16, in comparison to HPV types 6 and 11, is more often associated with malignant genital cancers in humans.
Similarity: Belongs to the papillomaviridae E2 protein family. {ECO:0000255|HAMAP-Rule:MF_04001}.

Annotations taken from UniProtKB at the EBI.