KEGG   PATHWAY: ocu05161
ocu05161                    Pathway                                
Hepatitis B - Oryctolagus cuniculus (rabbit)
Hepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and converted into a covalently closed circular molecule cccDNA. The cccDNA is the template for transcription of all viral RNAs including the pregenomic RNA (pgRNA), encoding for 7 viral proteins: large, middle, and small envelope proteins (LHBs, MHBs, and SHBs) that form the surface antigen (HBsAg), the core antigen (HBcAg), the e antigen (HBeAg), the HBV polymerase, and the regulatory protein X (HBx). The pgRNA interacts with the viral polymerase protein to initiate the encapsidation into the core particles. Through endoplasmic reticulum, the core particles finish assembling with the envelope proteins and are released. HBV infection leads to a wide spectrum of liver diseases raging from chronic hepatitis, cirrhosis to hepatocellular carcinoma. The mechanism of liver injury is still not clear. However, HBV proteins target host proteins, involved in a variety of functions, thus regulating transcription, cellular signaling cascades, proliferation, differentiation, and apoptosis.
Human Diseases; Infectious disease: viral
Pathway map
ocu05161  Hepatitis B

Oryctolagus cuniculus (rabbit) [GN:ocu]
100340334  HSPG2; heparan sulfate proteoglycan 2 [KO:K06255]
100009555  SLC10A1; solute carrier family 10 member 1 [KO:K14341]
103345451  transforming growth factor beta-1 [KO:K13375]
108175468  transforming growth factor beta-1-like [KO:K13375]
100352552  transforming growth factor beta-1 [KO:K13375]
100352810  transforming growth factor beta-1 [KO:K13375]
103345452  transforming growth factor beta-1-like [KO:K13375]
100352301  transforming growth factor beta-1 [KO:K13375]
100353067  transforming growth factor beta-1 [KO:K13375]
103345448  transforming growth factor beta-1 [KO:K13375]
100008645  TGFB1; transforming growth factor beta-1 [KO:K13375]
100009371  TGFB2; transforming growth factor beta 2 [KO:K13376]
100358982  TGFB3; transforming growth factor beta 3 [KO:K13377]
100345812  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:]
100344335  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:]
100346303  SMAD3; SMAD family member 3 [KO:K23605]
100348489  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
100346929  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
100342664  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
100337999  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
100327265  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100351345  EGR2; early growth response 2 [KO:K12496]
100355500  EGR3; early growth response 3 [KO:K12497]
100354135  EP300; E1A binding protein p300 [KO:K04498] [EC:]
100340619  CREBBP; CREB binding protein [KO:K04498] [EC:]
100344073  FASLG; Fas ligand [KO:K04389]
100354475  DDB1; damage specific DNA binding protein 1 [KO:K10610]
100352386  DDB2; damage specific DNA binding protein 2 [KO:K10140]
100348484  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:]
100358299  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
100008930  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100342694  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
100344852  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:]
100348663  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
100345181  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
100337822  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
100357841  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100345250  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100342852  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
100353706  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
100355888  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:]
100356401  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
100328905  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100357341  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100349426  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100008993  MMP9; matrix metallopeptidase 9 [KO:K01403] [EC:]
103349397  BCL2; BCL2, apoptosis regulator [KO:K02161]
100358587  BAD; BCL2 associated agonist of cell death [KO:K02158]
100008609  FAS; Fas cell surface death receptor [KO:K04390]
103346753  FADD; Fas associated via death domain [KO:K02373]
100348477  CASP8; caspase 8 [KO:K04398] [EC:]
100101580  CASP10; caspase 10 [KO:K04400] [EC:]
100355991  BID; BH3 interacting domain death agonist [KO:K04726]
100355675  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103348383  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
100357840  cytochrome c-like [KO:K08738]
100355084  cytochrome c [KO:K08738]
100341050  cytochrome c-like [KO:K08738]
100354468  cytochrome c-like [KO:K08738]
100357329  cytochrome c [KO:K08738]
100341515  cytochrome c-like [KO:K08738]
100353673  cytochrome c, testis-specific [KO:K08738]
100351037  cytochrome c-like [KO:K08738]
100341175  cytochrome c [KO:K08738]
103347723  cytochrome c-like [KO:K08738]
100354724  cytochrome c-like [KO:K08738]
103351673  cytochrome c-like [KO:K08738]
108178730  cytochrome c-like [KO:K08738]
108177422  cytochrome c-like [KO:K08738]
100101592  CASP9; caspase 9 [KO:K04399] [EC:]
100008840  CASP3; caspase 3 [KO:K02187] [EC:]
103350677  caspase-12 [KO:K04741] [EC:3.4.22.-]
103346801  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
100009292  TP53; tumor protein p53 [KO:K04451]
100358389  CCNA1; cyclin A1 [KO:K06627]
100134866  CCNA2; cyclin A2 [KO:K06627]
100134865  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:]
100134864  CCNE1; cyclin E1 [KO:K06626]
100134867  CCNE2; cyclin E2 [KO:K06626]
100357431  RB1; RB transcriptional corepressor 1 [KO:K06618]
100356957  E2F1; E2F transcription factor 1 [KO:K17454]
100346379  E2F2; E2F transcription factor 2 [KO:K09389]
100353173  E2F3; E2F transcription factor 3 [KO:K06620]
100349774  V-type proton ATPase subunit S1-like [KO:K03662]
100328760  ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]
100037720  PRKCA; protein kinase C alpha [KO:K02677] [EC:]
100037719  PRKCB; protein kinase C beta [KO:K19662] [EC:]
100009102  PRKCG; protein kinase C gamma [KO:K19663] [EC:]
100352378  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
100353824  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
100008859  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
100347003  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
100009088  TNF; tumor necrosis factor [KO:K03156]
100352594  JAK1; Janus kinase 1 [KO:K11217] [EC:]
100358134  JAK2; Janus kinase 2 [KO:K04447] [EC:]
100344622  TYK2; tyrosine kinase 2 [KO:K11219] [EC:]
100348778  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
100343893  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
100344467  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
100344146  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
100348518  signal transducer and activator of transcription 5A [KO:K11223]
100348267  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100344264  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
100008752  VDAC3; voltage dependent anion channel 3 [KO:K15041]
100342358  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:]
100341599  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:]
100342500  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100356615  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
100346391  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
100347487  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
100344241  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100008856  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100338341  EIF5A; eukaryotic translation initiation factor 5A [KO:K04448]
100342294  SMAD4; SMAD family member 4 [KO:K04501]
100355367  ATF2; activating transcription factor 2 [KO:K04450]
100351999  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100358175  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
100343130  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
100345475  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
100357876  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
100339383  ATF4; activating transcription factor 4 [KO:K04374]
100357483  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
100357489  ATF6B; activating transcription factor 6 beta [KO:K09049]
100009129  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
100339381  PCNA; proliferating cell nuclear antigen [KO:K04802]
100340437  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:]
100351964  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:]
100347407  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
100009316  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100347345  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
100348561  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100338345  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
100340952  ELK1; ELK1, ETS transcription factor [KO:K04375]
100009578  TLR2; toll like receptor 2 [KO:K10159]
100340811  MYD88; myeloid differentiation primary response 88 [KO:K04729]
100338708  TIRAP; TIR domain containing adaptor protein [KO:K05403]
100009497  TLR4; toll like receptor 4 [KO:K10160]
100341605  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:]
100354743  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:]
100343190  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:]
100358246  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
100342249  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
100343571  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
100008733  IL6; interleukin 6 [KO:K05405]
100339953  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:]
100355230  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:]
100350614  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
103346035  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
100344161  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
100341695  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
103345313  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:]
100345225  TICAM2; toll-like receptor adaptor molecule 2 [KO:K05409]
100009024  TLR3; toll like receptor 3 [KO:K05401]
100347707  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:]
100343560  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:]
100356540  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
100359083  TRAF3; TNF receptor associated factor 3 [KO:K03174]
100354455  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:]
100358771  TBK1; TANK binding kinase 1 [KO:K05410] [EC:]
100348597  DDX3X; DEAD-box helicase 3, X-linked [KO:K11594] [EC:]
103346571  IRF3; interferon regulatory factor 3 [KO:K05411]
100358763  IRF7; interferon regulatory factor 7 [KO:K09447]
100353390  interferon alpha-21-like [KO:K05414]
100355669  interferon alpha-21-like [KO:K05414]
100355912  interferon alpha-5-like [KO:K05414]
100357708  interferon alpha-21-like [KO:K05414]
100354654  interferon alpha-21-like [KO:K05414]
100356419  interferon alpha-14-like [KO:K05414]
100357194  interferon alpha-21-like [KO:K05414]
100356678  interferon alpha-1/13-like [KO:K05414]
100342931  IFNB1; interferon beta 1 [KO:K05415]
100338604  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
C00076  Calcium cation
Caballero A, Tabernero D, Buti M, Rodriguez-Frias F
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
Antiviral Res 158:34-44 (2018)
Walsh R, Locarnini S
Hepatitis B precore protein: pathogenic potential and therapeutic promise.
Yonsei Med J 53:875-85 (2012)
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Present and future therapies of hepatitis B: From discovery to cure.
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Viral life cycle of hepatitis B virus: Host factors and druggable targets.
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Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease.
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Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.
Hepatology 49:1203-17 (2009)
Yoo YG, Lee MO
Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor.
J Biol Chem 279:36242-9 (2004)
Zhang X, Zhang H, Ye L
Effects of hepatitis B virus X protein on the development of liver cancer.
J Lab Clin Med 147:58-66 (2006)
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Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.
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Liver cell transformation in chronic HBV infection.
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X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.
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Chronic hepatitis B in hepatocarcinogenesis.
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Interference of Apoptosis by Hepatitis B Virus.
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Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues.
J Med Virol 77:374-81 (2005)
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Hepatitis B virus X protein induces apoptosis by enhancing translocation of Bax to mitochondria.
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Hepatitis B virus X gene and hepatocarcinogenesis.
J Gastroenterol 46:974-90 (2011)
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The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-binding protein.
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Hepatitis viruses and the MAPK pathway: is this a survival strategy?
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HBx protein of hepatitis B virus activates Jak1-STAT signaling.
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Viral hepatocarcinogenesis: from infection to cancer.
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Cytobiological consequences of calcium-signaling alterations induced by human viral proteins.
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Hepatitis B viral HBx induces matrix metalloproteinase-9 gene expression through activation of ERK and PI-3K/AKT pathways: involvement of invasive potential.
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Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKepsilon and DDX3.
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ocu04010  MAPK signaling pathway
ocu04064  NF-kappa B signaling pathway
ocu04110  Cell cycle
ocu04115  p53 signaling pathway
ocu04151  PI3K-Akt signaling pathway
ocu04210  Apoptosis
ocu04620  Toll-like receptor signaling pathway
ocu04622  RIG-I-like receptor signaling pathway
ocu04630  JAK-STAT signaling pathway
KO pathway

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