Table 1.

The properties and functions of HPV proteins.

Protein Name	Molecular Weight	Number of Amino Acids	Function	References
E1	73 kDa	649	− DNA helicase − initiation of viral DNA replication − forms a replication complex with E2 − binds to the p62 protein subunit of the human homolog of transcription factor TFHII and the p80 protein − interaction with DNA polymerase alpha	[31,32,33]
E2	42 kDa	365	− initiation of viral DNA replication − transcription factor − interaction with the E1 protein, bromodomain-containing protein 4 (Brd4), DNA topoisomerase II-binding protein 1 (TopBP1) − control of early region viral gene expression	[34,35]
E4	10.5 kDa	92	− involves cell cycle arrest − disruption of keratin filaments − expressed as an E1^E4 transcript	[36,37,38]
E5	9.4 kDa	83	− transmembrane protein − localized in the Golgi apparatus − regulates growth signaling pathways via activation of the epidermal growth factor receptor (EGFR), downstream regulation of the Ras–Raf–MAP kinase pathway or the PI3K–Akt pathway − proliferation of the altered cell − inhibition of apoptosis due to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the Fas ligand (FasL) − prevents formation of the death-inducing signaling complex (DISC) induced by TRAIL − interaction with MHC/HLA class I − stimulation of interferon β1 (IFNβ1) and interferon regulatory factor 1 (IRF-1) − interaction with other oncoproteins − interaction with vacuolar ATPase, platelet-derived growth factor (PDGF), zinc transporter ZnT1, protocadherin 1 (PCDH1)	[39,40,41,42,43,44,45]
E6	18–19.2 kDa	150	− oncoprotein − p53 protein degradation − upregulation of the expression of hTERT telomerase − interaction with caspase 8 − cell cycle deregulation − collaborative action with the E7 protein leads to malignant transformation − interaction with the Bak protein − interaction with the Bax protein − interaction with E6AP ubiquitin ligase that is essential for E6 stability − interaction with HECT domain-containing ubiquitin ligase EDD − interaction with proteins containing PDZ domains	[19,46,47,48,49,50,51,52,53,54]
E7	11 kDa	98	− oncoprotein − pRB inactivation − interaction with centromere protein C (CENP-C) − functional inactivation permitting cell progression to the S-phase of cell cycle − uncontrolled cell division − collaborative action with the E6 protein leads to malignant transformation − interaction with cellular non-receptor protein tyrosine phosphatase PTPN14 − interaction with the pRB-related members of the pocket protein family like p107 and p130 involved in cell cycle regulation − association with the 600 kDa retinoblastoma protein-associated factor (p600) − association with members of the cullin 2 (Cul2) ubiquitin ligase complex	[55,56,57,58,59,60,61]
L1	55 kDa	531	− major capsid protein of a virus-like particle (VLP) − binding of the basal membrane of keratinocytes substantively to heparin sulfate proteoglycans (HSPG) − attends in the mechanism of viral entry by binding to the α6 integrin	[62,63]
L2	74 kDa	462	− minor protein of the capsid − promotes the transportation of the virion into the nucleus of the host cell by interacting with host dynein following endosomal entry − interaction with the Kapα2β1, Kapβ2, and Kapβ3 receptors − mediates the egress of the viral genome from endosomes	[9,30,64,65]