The papillomavirus E4 open reading frame (ORF) is contained within the E2 ORF, with the primary E4 gene-product (E1∧E4) being translated from a spliced mRNA that includes the E1 initiation codon and adjacent sequences. E4 is located centrally within the E2 gene, in a region that encodes the E2 protein′s flexible hinge domain. Although a number of minor E4 transcripts have been reported, it is the product of the abundant E1∧E4 mRNA that has been most extensively analysed.
Function:
Plays several roles to favor viral DNA replication including disruption of host intranuclear speckles (termed ND10 body) organization, cell cycle arrest at the G2 phase and inhibition of cellular DNA replication, by preventing loading of host replication licensing proteins MCM2 and MCM7 onto chromatin. Additionally, E4 is found in inclusion bodies within the cytoplasm associated with host SRPK1, a splicing factor regulator. Therefore, E4 may regulate host splicing factors in order to favor expression of late viral transcripts. Late in the infectious cycle, E4 may also act to diminish the integrity of the keratinocyte by disrupting the keratin cytoskeleton and inducing apoptosis through alteration of mitochondrial function to facilitate egress of the newly formed virions.
Subunit:
Assembles into oligomeric complexes. Interacts with host SRPK1; this interaction may favor expression of late viral transcripts. Interacts with host cytokeratin components KRT8 and KRT18.
Subcellular Location:
Host cytoplasm. Host nucleus.
Post-translational modifications:
Phosphorylated by host ERK. The phosphorylation triggers a structural change that enhances keratin binding and protein stability.
Similarity:
Belongs to the papillomaviridae E4 protein family.
SWISS:
P03107
Gene ID:
1489076
Database links:
Entrez Gene: 1489076 HPV16
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