ID   VE4_HPV6B               Reviewed;          91 AA.
AC   P06459;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   03-AUG-2022, entry version 61.
DE   RecName: Full=Protein E4;
DE   AltName: Full=E1^E4;
GN   Name=E4;
OS   Human papillomavirus type 6b.
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC   Alphapapillomavirus.
OX   NCBI_TaxID=10600;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6321162; DOI=10.1002/j.1460-2075.1983.tb01744.x;
RA   Schwarz E., Durst M., Demankowski C., Lattermann O., Zech R.,
RA   Wolfsperger E., Suhai S., zur Hausen H.;
RT   "DNA sequence and genome organization of genital human papillomavirus type
RT   6b.";
RL   EMBO J. 2:2341-2348(1983).
RN   [2]
RP   CONCEPTUAL TRANSLATION.
RA   Desaintes C.;
RL   Unpublished observations (FEB-1998).
CC   -!- FUNCTION: Associates with keratin intermediate filaments in certain
CC       epithelial cells in culture.
CC   -!- FUNCTION: Contributes to multiple aspects of the viral life cycle
CC       including viral genome amplification, suppression of suprabasal cell
CC       differentiation and egress of newly formed virions. Induces host cell
CC       cycle arrest at the G2 phase by associating with and preventing the
CC       nuclear entry of host CDK1/cyclin B1 complexes. Inhibits cellular DNA
CC       replication by preventing loading of host replication licensing
CC       proteins MCM2 and MCM7 onto chromatin. Within the cytoplasm, associates
CC       with host kinase SRPK1, a splicing factor regulator, and inhibits its
CC       activity. Therefore, E4 favors expression of late viral transcripts by
CC       inhibiting SRPK1-mediated phosphorylation of host serine-arginine (SR)
CC       proteins that have critical roles in mRNA metabolism. Late in the
CC       infectious cycle, E4 also acts to diminish the integrity of the
CC       keratinocyte by disrupting the keratin cytoskeleton and inducing
CC       apoptosis through alteration of mitochondrial function to facilitate
CC       egress of the newly formed virions. {ECO:0000250|UniProtKB:P06922}.
CC   -!- SUBUNIT: Assembles into oligomeric complexes. Interacts with host CDK1.
CC       Interacts with host SRPK1; this interaction may favor expression of
CC       late viral transcripts. Interacts with host cytokeratin components KRT8
CC       and KRT18. {ECO:0000250|UniProtKB:P06922}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:P06922}.
CC       Host nucleus {ECO:0000250|UniProtKB:P06922}.
CC   -!- PTM: Phosphorylated by host ERK. The phosphorylation triggers a
CC       structural change that enhances keratin binding and protein stability.
CC       {ECO:0000250|UniProtKB:P06922}.
CC   -!- MISCELLANEOUS: The major E4 form is first synthesized as an E1^E4
CC       fusion protein from spliced E1^E4 transcripts, such that the first few
CC       amino acids of the E4 protein are derived from the N terminus of E1.
CC       {ECO:0000250|UniProtKB:P06922}.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E4 protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA25022.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X00203; CAA25020.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; X00203; CAA25022.1; ALT_SEQ; Genomic_DNA.
DR   PIR; C20558; W4WL6.
DR   RefSeq; NP_040298.1; NC_001355.1.
DR   RefSeq; NP_040300.1; NC_001355.1.
DR   SMR; P06459; -.
DR   PRIDE; P06459; -.
DR   GeneID; 1489363; -.
DR   GeneID; 1489365; -.
DR   KEGG; vg:1489363; -.
DR   KEGG; vg:1489365; -.
DR   Proteomes; UP000007676; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0039592; P:suppression by virus of G2/M transition of host mitotic cell cycle; IEA:UniProtKB-KW.
DR   InterPro; IPR003861; Papilloma_E4.
DR   Pfam; PF02711; Pap_E4; 1.
PE   3: Inferred from homology;
KW   Early protein; Host cytoplasm; Host G2/M cell cycle arrest by virus;
KW   Host nucleus; Host-virus interaction;
KW   Modulation of host cell cycle by virus; Phosphoprotein.
FT   CHAIN           1..91
FT                   /note="Protein E4"
FT                   /id="PRO_0000133260"
FT   REGION          15..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   91 AA;  10173 MW;  21C497F345070227 CRC64;
     MADDSALHKK YPFLNLLHTP PHRPPPLCPQ APRKTQCKRR LGNEHEESNS PLATPCVWPT
     LDPWTVETTT SSLTITTSTK DGTTVTVQLR L