ENTRY ko05165 Pathway NAME Human papillomavirus infection DESCRIPTION Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus. HPV infect mucoal and cutaneous epithelium resulting in several types of pathologies, most notably, cervical cancer. All types of HPV share a common genomic structure and encode eight proteins: E1, E2, E4, E5, E6, and E7 (early) and L1 and L2 (late). It has been demonstrated that E1 and E2 are involved in viral transcription and replication. The functions of the E4 protein is not yet fully understood. E5, E6, and E7 act as oncoproteins. E5 inhibits the V-ATPase, prolonging EGFR signaling and thereby promoting cell proliferation. The expression of E6 and E7 not only inhibits the tumor suppressors p53 and Rb, but also alters additional signalling pathways. Among these pathways, PI3K/Akt signalling cascade plays a very important role in HPV-induced carcinogenesis. The L1 and L2 proteins form icosahedral capsids for progeny virion generation. CLASS Human Diseases; Infectious disease: viral PATHWAY_MAP ko05165 Human papillomavirus infection DRUG D02783 Afovirsen sodium (USAN) D06555 Amolimogene bepiplasmid (USAN) D06666 Verpasep caltespen (USAN/INN) ORTHOLOGY K03209 wingless-type MMTV integration site family, member 1 K00182 wingless-type MMTV integration site family, member 2 K00312 wingless-type MMTV integration site family, member 3 K00408 wingless-type MMTV integration site family, member 4 K00444 wingless-type MMTV integration site family, member 5 K00445 wingless-type MMTV integration site family, member 6 K00572 wingless-type MMTV integration site family, member 7 K00714 wingless-type MMTV integration site family, member 8 K01064 wingless-type MMTV integration site family, member 9 K01357 wingless-type MMTV integration site family, member 10 K01384 wingless-type MMTV integration site family, member 11 K01558 wingless-type MMTV integration site family, member 16 K02432 frizzled 1/7 K02235 frizzled 2 K02329 frizzled 3 K02354 frizzled 4 K02375 frizzled 5/8 K02376 frizzled 6 K02842 frizzled 9/10 K02353 segment polarity protein dishevelled K21807 Alphapapillomavirus protein E6 K03083 glycogen synthase kinase 3 beta [EC:2.7.11.26] K02157 axin 1 K04385 axin 2 K02085 adenomatosis polyposis coli protein K02105 catenin beta 1 K08957 casein kinase 1, alpha [EC:2.7.11.1] K11126 telomerase reverse transcriptase [EC:2.7.7.49] K02620 transcription factor 7 K04490 transcription factor 7-like 1 K04491 transcription factor 7-like 2 K10587 ubiquitin-protein ligase E3 A [EC:2.3.2.26] K05401 toll-like receptor 3 K05842 toll-like receptor adapter molecule 1 K03174 TNF receptor-associated factor 3 K07211 inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10] K05410 TANK-binding kinase 1 [EC:2.7.11.10] K05411 interferon regulatory factor 3 K05415 interferon beta K04498 E1A/CREB-binding protein [EC:2.3.1.48] K11315 transcriptional adapter 3 K04451 tumor protein p53 K19260 Papillomaviridae major capsid protein L1 K21808 Alphapapillomavirus minor capsid protein L2 K05631 atrophin-1 interacting protein 3 (BAI1-associated protein 1) K01110 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67] K04237 partitioning defective protein 3 K06093 partitioning defective protein 6 K06069 atypical protein kinase C iota type [EC:2.7.11.13] K18952 atypical protein kinase C zeta type [EC:2.7.11.13] K04393 cell division control protein 42 K16175 protein scribble K12076 disks large protein 1 K12075 discs large protein 2 K21098 discs large protein 3 K06094 lethal(2) giant larvae protein K06090 crumbs 3 K06092 InaD-like protein K06091 MAGUK p55 subfamily member 5 K03900 von Willebrand factor K16857 thrombospondin 1 K04659 thrombospondin 2/3/4/5 K05717 fibronectin 1 K06236 collagen type I alpha K19719 collagen type II alpha K06237 collagen type IV alpha K06238 collagen type VI alpha K08131 collagen type IX alpha K05637 laminin, alpha 1/2 K06240 laminin, alpha 3/5 K06241 laminin, alpha 4 K05636 laminin, beta 1 K06243 laminin, beta 2 K06244 laminin, beta 3 K06245 laminin, beta 4 K05635 laminin, gamma 1 K06246 laminin, gamma 2 K06247 laminin, gamma 3 K06248 chondroadherin K06249 reelin [EC:3.4.21.-] K06250 secreted phosphoprotein 1 K06251 vitronectin K06252 tenascin K06253 integrin binding sialoprotein K06480 integrin alpha 1 K06481 integrin alpha 2 K06476 integrin alpha 2B K06482 integrin alpha 3 K06483 integrin alpha 4 K06484 integrin alpha 5 K06485 integrin alpha 6 K06583 integrin alpha 7 K06584 integrin alpha 8 K06585 integrin alpha 9 K06586 integrin alpha 10 K06587 integrin alpha 11 K06487 integrin alpha V K05719 integrin beta 1 K06493 integrin beta 3 K06525 integrin beta 4 K06588 integrin beta 5 K06589 integrin beta 6 K06590 integrin beta 7 K06591 integrin beta 8 K05725 focal adhesion kinase 1 [EC:2.7.10.2] K05760 paxillin K03156 tumor necrosis factor superfamily, member 2 K03158 tumor necrosis factor receptor superfamily member 1A K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein K04389 tumor necrosis factor ligand superfamily member 6 K04390 tumor necrosis factor receptor superfamily member 6 K02373 FAS-associated death domain protein K04398 caspase 8 [EC:3.4.22.61] K02187 caspase 3 [EC:3.4.22.56] K13365 sodium/hydrogen exchange regulatory cofactor NHE-RF1 K21809 Alphapapillomavirus protein E7 K04382 serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16] K03456 serine/threonine-protein phosphatase 2A regulatory subunit A K04354 serine/threonine-protein phosphatase 2A regulatory subunit B K11583 serine/threonine-protein phosphatase 2A regulatory subunit B'' K11584 serine/threonine-protein phosphatase 2A regulatory subunit B' K07206 tuberous sclerosis 1 K07207 tuberous sclerosis 2 K07208 Ras homolog enriched in brain K07203 serine/threonine-protein kinase mTOR [EC:2.7.11.1] K07205 eukaryotic translation initiation factor 4E binding protein 1 K04688 ribosomal protein S6 kinase beta [EC:2.7.11.1] K21810 Alphapapillomavirus replication protein E1 [EC:5.6.2.-] K21811 Alphapapillomavirus regulatory protein E2 K14021 Bcl-2 homologous antagonist/killer K02158 Bcl-2-antagonist of cell death K05089 platelet-derived growth factor receptor beta [EC:2.7.10.1] K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K07201 forkhead box protein O1 K21812 Alphapapillomavirus protein E5 K06624 cyclin-dependent kinase inhibitor 1B K06625 cyclin-dependent kinase inhibitor 1A K04503 G1/S-specific cyclin-D1 K10151 G1/S-specific cyclin-D2 K10152 G1/S-specific cyclin-D3 K02089 cyclin-dependent kinase 4 [EC:2.7.11.22] K02091 cyclin-dependent kinase 6 [EC:2.7.11.22] K06626 G1/S-specific cyclin-E1 K02206 cyclin-dependent kinase 2 [EC:2.7.11.22] K06618 retinoblastoma-associated protein K04681 retinoblastoma-like protein 1 K16332 retinoblastoma-like protein 2 K03062 26S proteasome regulatory subunit T2 K17454 transcription factor E2F1 K06627 cyclin-A K04728 serine-protein kinase ATM [EC:2.7.11.1] K06640 serine/threonine-protein kinase ATR [EC:2.7.11.1] K05448 vascular endothelial growth factor A K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10] K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10] K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma K02580 nuclear factor NF-kappa-B p105 subunit K04735 transcription factor p65 K06643 E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27] K12236 transcriptional repressor NF-X1 K06067 histone deacetylase 1/2 [EC:3.5.1.98] K11643 chromodomain-helicase-DNA-binding protein 4 [EC:5.6.2.-] K09444 interferon regulatory factor 1 K03120 transcription initiation factor TFIID TATA-box-binding protein K06751 MHC class I antigen K14009 B-cell receptor-associated protein 31 K02145 V-type H+-transporting ATPase subunit A [EC:7.1.2.2] K02147 V-type H+-transporting ATPase subunit B K02148 V-type H+-transporting ATPase subunit C K02149 V-type H+-transporting ATPase subunit D K02150 V-type H+-transporting ATPase subunit E K02151 V-type H+-transporting ATPase subunit F K02152 V-type H+-transporting ATPase subunit G K02144 V-type H+-transporting ATPase subunit H K02154 V-type H+-transporting ATPase subunit a K02146 V-type H+-transporting ATPase subunit d K02153 V-type H+-transporting ATPase subunit e K02155 V-type H+-transporting ATPase 16kDa proteolipid subunit K03661 V-type H+-transporting ATPase 21kDa proteolipid subunit K03662 V-type H+-transporting ATPase S1 subunit K04357 epidermal growth factor K04361 epidermal growth factor receptor [EC:2.7.10.1] K04364 growth factor receptor-bound protein 2 K03099 son of sevenless K02833 GTPase HRas K07827 GTPase KRas K07828 GTPase NRas K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] K04368 mitogen-activated protein kinase kinase 1 [EC:2.7.12.2] K04369 mitogen-activated protein kinase kinase 2 [EC:2.7.12.2] K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] K11987 prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1] K04261 prostaglandin E receptor 4 K04632 guanine nucleotide-binding protein G(s) subunit alpha K04345 protein kinase A [EC:2.7.11.11] K02159 apoptosis regulator BAX K05870 cyclic AMP-responsive element-binding protein 1 K09048 cyclic AMP-responsive element-binding protein 3 K09047 cyclic AMP-responsive element-binding protein 5 K10691 E3 ubiquitin-protein ligase UBR4 [EC:2.3.2.27] K10389 tubulin gamma K00873 pyruvate kinase [EC:2.7.1.40] K05414 interferon alpha K05130 interferon receptor 1 K05131 interferon receptor 2 K11217 Janus kinase 1 [EC:2.7.10.2] K11219 non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2] K11220 signal transducer and activator of transcription 1 K11221 signal transducer and activator of transcription 2 K04693 interferon regulatory factor 9 K16195 eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1] K14608 2'-5'-oligoadenylate synthase-like protein K14754 interferon-induced GTP-binding protein Mx K12159 ubiquitin cross-reactive protein K06052 jagged-1 K02599 Notch 1 K20994 Notch 2 K20995 Notch 3 K20996 Notch 4 K04505 presenilin 1 [EC:3.4.23.-] K05948 fringe [EC:2.4.1.222] K06061 mastermind K06053 recombining binding protein suppressor of hairless K06054 hairy and enhancer of split 1 K09087 hairy and enhancer of split 2/6/7 K09088 hairy and enhancer of split 3 K09089 hairy and enhancer of split 4 K06055 hairy and enhancer of split 5 K09091 hairy and enhancer of split related with YRPW motif COMPOUND C00575 3',5'-Cyclic AMP C00584 Prostaglandin E2 C05981 Phosphatidylinositol-3,4,5-trisphosphate REFERENCE PMID:20592731 AUTHORS Moody CA, Laimins LA TITLE Human papillomavirus oncoproteins: pathways to transformation. 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JOURNAL Mol Cell Biol 28:4819-28 (2008) DOI:10.1128/MCB.01969-07 REFERENCE PMID:23536685 AUTHORS Raff AB, Woodham AW, Raff LM, Skeate JG, Yan L, Da Silva DM, Schelhaas M, Kast WM TITLE The evolving field of human papillomavirus receptor research: a review of binding and entry. JOURNAL J Virol 87:6062-72 (2013) DOI:10.1128/JVI.00330-13 REL_PATHWAY ko04064 NF-kappa B signaling pathway ko04110 Cell cycle ko04115 p53 signaling pathway ko04150 mTOR signaling pathway ko04151 PI3K-Akt signaling pathway ko04210 Apoptosis ko04310 Wnt signaling pathway ko04330 Notch signaling pathway ko04510 Focal adhesion ko04520 Adherens junction ko04530 Tight junction ko04612 Antigen processing and presentation ko04620 Toll-like receptor signaling pathway ko04630 JAK-STAT signaling pathway ///