KEGG   PATHWAY: hsa05161
Entry
hsa05161                    Pathway                                
Name
Hepatitis B - Homo sapiens (human)
Description
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.
Class
Human Diseases; Infectious disease: viral
Pathway map
hsa05161  Hepatitis B
hsa05161

Network
nt06162  Hepatitis B virus (HBV)
nt06214  PI3K signaling (cancer)
nt06263  Hepatocellular carcinoma
nt06507  TGFB signaling
nt06517  TLR signaling
nt06518  JAK-STAT signaling
nt06519  RLR signaling
nt06524  Apoptosis
  Element
N00267  HBV HBx to PI3K signaling pathway
N00268  HBV HBx to RIG-I-like receptor signaling pathway
N00531  HBV HBx to TGF-beta signaling pathway
N00532  HBV HBx to Egr-mediated transcription
N00533  HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00534  HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00535  HBV HBx to p53-mediated transcription
N00537  HBV HBx to cell cycle G1/S
N00539  HBV HBx to Ca2+-PYK2-RAS-ERK signaling pathway
N00540  HBV HBx to RAS-ERK signaling pathway
N00541  HBV HBx to RAS-ERK signaling pathway
N00543  HBV HBx to JNK signaling pathway
N00544  HBV HBx to CREB-mediated transcription
N00545  HBV HBx to ERK signaling pathway
N00547  HBV LHBs to PKC-ERK signaling pathway
N00548  HBV HBx to Jak-STAT signaling pathway
N00551  HBV HBs to TLR2/4-MAPK signaling pathway
N00552  HBV pol to TLR3-IRF3 signaling pathway
N00554  HBV HBe to TLR4-IRF3/7 signaling pathway
N00556  HBV HBe to TLR2/4-NFKB signaling pathway
N00558  HBV pol to IFN signaling pathway
Disease
H00412  Hepatitis B; Hepatitis B virus (HBV) infection
Drug
D02745  Interferon alfa-2b (USAN)
D02747  Peginterferon alfa-2a (USAN/INN)
D03305  Interferon alfa (NAMALWA) (JP19)
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; RAC-gamma serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
100506742  CASP12; inactive caspase-12 [KO:K04741] [EC:3.4.22.-]
1017  CDK2; cyclin-dependent kinase 2 isoform 1 [KO:K02206] [EC:2.7.11.22]
1026  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform 1 [KO:K06625]
10454  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform alpha [KO:K04403]
10488  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
10971  YWHAQ; 14-3-3 protein theta [KO:K16197]
110117499  P3R3URF-PIK3R3; LOC110117498-PIK3R3 readthrough [KO:K02649]
114609  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform a [KO:K05403]
1147  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467] [EC:2.7.11.10]
1385  CREB1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
1386  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform 1 [KO:K04450]
1387  CREBBP; CREB-binding protein isoform a [KO:K04498] [EC:2.3.1.48]
1388  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform a [KO:K09049]
1432  MAPK14; mitogen-activated protein kinase 14 isoform 2 [KO:K04441] [EC:2.7.11.24]
148022  TICAM1; TIR domain-containing adapter molecule 1 isoform 1 [KO:K05842]
148327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
1642  DDB1; DNA damage-binding protein 1 [KO:K10610]
1643  DDB2; DNA damage-binding protein 2 isoform WT [KO:K10140]
1654  DDX3X; ATP-dependent RNA helicase DDX3X isoform 1 [KO:K11594] [EC:5.6.2.7]
1869  E2F1; transcription factor E2F1 [KO:K17454]
1870  E2F2; transcription factor E2F2 [KO:K09389]
1871  E2F3; transcription factor E2F3 isoform 1 [KO:K06620]
1959  EGR2; E3 SUMO-protein ligase EGR2 isoform a [KO:K12496]
1960  EGR3; early growth response protein 3 isoform 1 [KO:K12497]
2002  ELK1; ETS domain-containing protein Elk-1 isoform a [KO:K04375]
2033  EP300; histone acetyltransferase p300 isoform 1 [KO:K04498] [EC:2.3.1.48]
207  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
208  AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
2185  PTK2B; protein-tyrosine kinase 2-beta isoform a [KO:K05871] [EC:2.7.10.2]
23118  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform a [KO:K04404]
2353  FOS; protein c-Fos [KO:K04379]
23586  RIGI; antiviral innate immune response receptor RIG-I isoform 1 [KO:K12646] [EC:5.6.2.6]
2885  GRB2; growth factor receptor-bound protein 2 isoform 1 [KO:K04364]
29110  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
317  APAF1; apoptotic protease-activating factor 1 isoform c [KO:K02084]
3265  HRAS; GTPase HRas isoform 1 [KO:K02833]
332  BIRC5; baculoviral IAP repeat-containing protein 5 isoform 2 [KO:K08731]
3339  HSPG2; basement membrane-specific heparan sulfate proteoglycan core protein isoform b precursor [KO:K06255]
3439  IFNA1; interferon alpha-1 precursor [KO:K05414]
3440  IFNA2; interferon alpha-2 precursor [KO:K05414]
3441  IFNA4; interferon alpha-4 precursor [KO:K05414]
3442  IFNA5; interferon alpha-5 precursor [KO:K05414]
3443  IFNA6; interferon alpha-6 precursor [KO:K05414]
3444  IFNA7; interferon alpha-7 precursor [KO:K05414]
3445  IFNA8; interferon alpha-8 precursor [KO:K05414]
3446  IFNA10; interferon alpha-10 precursor [KO:K05414]
3447  IFNA13; interferon alpha-13 precursor [KO:K05414]
3448  IFNA14; interferon alpha-14 precursor [KO:K05414]
3449  IFNA16; interferon alpha-16 precursor [KO:K05414]
3451  IFNA17; interferon alpha-17 precursor [KO:K05414]
3452  IFNA21; interferon alpha-21 precursor [KO:K05414]
3454  IFNAR1; interferon alpha/beta receptor 1 isoform 2 precursor [KO:K05130]
3456  IFNB1; interferon beta precursor [KO:K05415]
353376  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
355  FAS; tumor necrosis factor receptor superfamily member 6 isoform 1 precursor [KO:K04390]
3551  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209] [EC:2.7.11.10]
356  FASLG; tumor necrosis factor ligand superfamily member 6 isoform 1 [KO:K04389]
3569  IL6; interleukin-6 isoform 1 precursor [KO:K05405]
3576  CXCL8; interleukin-8 isoform 1 precursor [KO:K10030]
3654  IRAK1; interleukin-1 receptor-associated kinase 1 isoform 1 [KO:K04730] [EC:2.7.11.1]
3661  IRF3; interferon regulatory factor 3 isoform 1 [KO:K05411]
3665  IRF7; interferon regulatory factor 7 isoform a [KO:K09447]
369  ARAF; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
3716  JAK1; tyrosine-protein kinase JAK1 isoform 1 [KO:K11217] [EC:2.7.10.2]
3717  JAK2; tyrosine-protein kinase JAK2 isoform a [KO:K04447] [EC:2.7.10.2]
3718  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
3725  JUN; transcription factor Jun [KO:K04448]
3845  KRAS; GTPase KRas isoform a [KO:K07827]
4088  SMAD3; mothers against decapentaplegic homolog 3 isoform 1 [KO:K23605]
4089  SMAD4; mothers against decapentaplegic homolog 4 isoform a [KO:K04501]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
4318  MMP9; matrix metalloproteinase-9 preproprotein [KO:K01403] [EC:3.4.24.35]
4609  MYC; myc proto-oncogene protein isoform 1 [KO:K04377]
4615  MYD88; myeloid differentiation primary response protein MyD88 isoform 2 [KO:K04729]
468  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
4772  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform F [KO:K04446]
4773  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332]
4775  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform 1 [KO:K17333]
4776  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform 2 [KO:K17334]
4790  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580]
4792  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
4893  NRAS; GTPase NRas [KO:K07828]
5111  PCNA; proliferating cell nuclear antigen [KO:K04802]
51135  IRAK4; interleukin-1 receptor-associated kinase 4 isoform a [KO:K04733] [EC:2.7.11.1]
5290  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649]
5296  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
537  ATP6AP1; V-type proton ATPase subunit S1 precursor [KO:K03662]
54205  CYCS; cytochrome c [KO:K08738]
5578  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta type isoform 1 [KO:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma type isoform 2 [KO:K19663] [EC:2.7.11.13]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 isoform 1 [KO:K04371] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
5604  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369] [EC:2.7.12.2]
5606  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform B [KO:K04432] [EC:2.7.12.2]
5608  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform 1 [KO:K04433] [EC:2.7.12.2]
5609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform 3 [KO:K04431] [EC:2.7.12.2]
572  BAD; bcl2-associated agonist of cell death [KO:K02158]
57506  MAVS; mitochondrial antiviral-signaling protein isoform 1 [KO:K12648]
581  BAX; apoptosis regulator BAX isoform alpha [KO:K02159]
5894  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366] [EC:2.7.11.1]
5925  RB1; retinoblastoma-associated protein isoform 1 [KO:K06618]
596  BCL2; apoptosis regulator Bcl-2 isoform alpha [KO:K02161]
5970  RELA; transcription factor p65 isoform 1 [KO:K04735]
6300  MAPK12; mitogen-activated protein kinase 12 isoform 1 [KO:K04441] [EC:2.7.11.24]
637  BID; BH3-interacting domain death agonist isoform 2 [KO:K04726]
64135  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
6416  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform 1 [KO:K04430] [EC:2.7.12.2]
64764  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform 1 [KO:K09048]
6554  SLC10A1; hepatic sodium/bile acid cotransporter [KO:K14341]
6654  SOS1; son of sevenless homolog 1 isoform 1 [KO:K03099]
6655  SOS2; son of sevenless homolog 2 isoform 1 [KO:K03099]
6714  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
673  BRAF; serine/threonine-protein kinase B-raf isoform 1 [KO:K04365] [EC:2.7.11.1]
6772  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform alpha [KO:K11220]
6773  STAT2; signal transducer and activator of transcription 2 isoform 1 [KO:K11221]
6774  STAT3; signal transducer and activator of transcription 3 isoform 1 [KO:K04692]
6775  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
6776  STAT5A; signal transducer and activator of transcription 5A isoform 1 [KO:K11223]
6777  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
6778  STAT6; signal transducer and activator of transcription 6 isoform 1 [KO:K11225]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform B [KO:K04427] [EC:2.7.11.25]
7040  TGFB1; transforming growth factor beta-1 proprotein preproprotein [KO:K13375]
7042  TGFB2; transforming growth factor beta-2 proprotein isoform 2 preproprotein [KO:K13376]
7043  TGFB3; transforming growth factor beta-3 proprotein isoform 1 preproprotein [KO:K13377]
7046  TGFBR1; TGF-beta receptor type-1 isoform 1 precursor [KO:K04674] [EC:2.7.11.30]
7048  TGFBR2; TGF-beta receptor type-2 isoform B precursor [KO:K04388] [EC:2.7.11.30]
7097  TLR2; toll-like receptor 2 precursor [KO:K10159]
7098  TLR3; toll-like receptor 3 precursor [KO:K05401]
7099  TLR4; toll-like receptor 4 isoform A precursor [KO:K10160]
7124  TNF; tumor necrosis factor [KO:K03156]
7157  TP53; cellular tumor antigen p53 isoform a [KO:K04451]
7187  TRAF3; TNF receptor-associated factor 3 isoform 1 [KO:K03174]
7189  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
7297  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform 2 [KO:K11219] [EC:2.7.10.2]
7419  VDAC3; non-selective voltage-gated ion channel VDAC3 isoform 1 [KO:K15041]
7529  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
7534  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
836  CASP3; caspase-3 isoform a preproprotein [KO:K02187] [EC:3.4.22.56]
841  CASP8; caspase-8 isoform 2 precursor [KO:K04398] [EC:3.4.22.61]
842  CASP9; caspase-9 isoform alpha precursor [KO:K04399] [EC:3.4.22.62]
843  CASP10; caspase-10 isoform 2 preproprotein [KO:K04400] [EC:3.4.22.63]
84699  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform a [KO:K09048]
8503  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649]
8517  IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210]
8772  FADD; FAS-associated death domain protein [KO:K02373]
890  CCNA2; cyclin-A2 [KO:K06627]
8900  CCNA1; cyclin-A1 [KO:K06627]
898  CCNE1; G1/S-specific cyclin-E1 isoform 1 [KO:K06626]
90993  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform 1 [KO:K09048]
9134  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
9586  CREB5; cyclic AMP-responsive element-binding protein 5 isoform alpha [KO:K09047]
9641  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 1 [KO:K07211] [EC:2.7.11.10]
Compound
C00076  Calcium cation
Reference
PMID:30059722
  Authors
Caballero A, Tabernero D, Buti M, Rodriguez-Frias F
  Title
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
  Journal
Antiviral Res 158:34-44 (2018)
DOI:10.1016/j.antiviral.2018.07.019
Reference
PMID:22869468
  Authors
Walsh R, Locarnini S
  Title
Hepatitis B precore protein: pathogenic potential and therapeutic promise.
  Journal
Yonsei Med J 53:875-85 (2012)
DOI:10.3349/ymj.2012.53.5.875
Reference
PMID:26239691
  Authors
Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS
  Title
Present and future therapies of hepatitis B: From discovery to cure.
  Journal
Hepatology 62:1893-908 (2015)
DOI:10.1002/hep.28025
Reference
PMID:26776362
  Authors
Morikawa K, Suda G, Sakamoto N
  Title
Viral life cycle of hepatitis B virus: Host factors and druggable targets.
  Journal
Hepatol Res 46:871-7 (2016)
DOI:10.1111/hepr.12650
Reference
PMID:19201080
  Authors
Feitelson MA, Reis HM, Tufan NL, Sun B, Pan J, Lian Z
  Title
Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease.
  Journal
Cancer Lett 286:69-79 (2009)
DOI:10.1016/j.canlet.2008.12.010
Reference
PMID:19263472
  Authors
Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, Kobayashi K, Yokote K, Koike K, Okazaki K
  Title
Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.
  Journal
Hepatology 49:1203-17 (2009)
DOI:10.1002/hep.22765
Reference
PMID:15173177
  Authors
Yoo YG, Lee MO
  Title
Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor.
  Journal
J Biol Chem 279:36242-9 (2004)
DOI:10.1074/jbc.M401290200
Reference
PMID:16459163
  Authors
Zhang X, Zhang H, Ye L
  Title
Effects of hepatitis B virus X protein on the development of liver cancer.
  Journal
J Lab Clin Med 147:58-66 (2006)
DOI:10.1016/j.lab.2005.10.003
Reference
PMID:19854353
  Authors
Benhenda S, Cougot D, Buendia MA, Neuveut C
  Title
Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.
  Journal
Adv Cancer Res 103:75-109 (2009)
DOI:10.1016/S0065-230X(09)03004-8
Reference
PMID:21994562
  Authors
Benhenda S, Cougot D, Neuveut C, Buendia MA
  Title
Liver cell transformation in chronic HBV infection.
  Journal
Viruses 1:630-46 (2009)
DOI:10.3390/v1030630
Reference
PMID:11099494
  Authors
Diao J, Khine AA, Sarangi F, Hsu E, Iorio C, Tibbles LA, Woodgett JR, Penninger J, Richardson CD
  Title
X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.
  Journal
J Biol Chem 276:8328-40 (2001)
DOI:10.1074/jbc.M006026200
Reference
PMID:16891440
  Authors
Park NH, Song IH, Chung YH
  Title
Chronic hepatitis B in hepatocarcinogenesis.
  Journal
Postgrad Med J 82:507-15 (2006)
DOI:10.1136/pgmj.2006.047431
Reference
PMID:28820498
  Authors
Lin S, Zhang YJ
  Title
Interference of Apoptosis by Hepatitis B Virus.
  Journal
Viruses 9:230 (2017)
DOI:10.3390/v9080230
Reference
PMID:16173017
  Authors
Zhang X, Dong N, Yin L, Cai N, Ma H, You J, Zhang H, Wang H, He R, Ye L
  Title
Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues.
  Journal
J Med Virol 77:374-81 (2005)
DOI:10.1002/jmv.20466
Reference
PMID:18481805
  Authors
Kim HJ, Kim SY, Kim J, Lee H, Choi M, Kim JK, Ahn JK
  Title
Hepatitis B virus X protein induces apoptosis by enhancing translocation of Bax to mitochondria.
  Journal
IUBMB Life 60:473-80 (2008)
DOI:10.1002/iub.68
Reference
PMID:21647825
  Authors
Ng SA, Lee C
  Title
Hepatitis B virus X gene and hepatocarcinogenesis.
  Journal
J Gastroenterol 46:974-90 (2011)
DOI:10.1007/s00535-011-0415-9
Reference
PMID:9195957
  Authors
Cong YS, Yao YL, Yang WM, Kuzhandaivelu N, Seto E
  Title
The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-binding protein.
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J Biol Chem 272:16482-9 (1997)
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Reference
PMID:12686421
  Authors
Panteva M, Korkaya H, Jameel S
  Title
Hepatitis viruses and the MAPK pathway: is this a survival strategy?
  Journal
Virus Res 92:131-40 (2003)
DOI:10.1016/S0168-1702(02)00356-8
Reference
PMID:9738022
  Authors
Lee YH, Yun Y
  Title
HBx protein of hepatitis B virus activates Jak1-STAT signaling.
  Journal
J Biol Chem 273:25510-5 (1998)
DOI:10.1074/jbc.273.39.25510
Reference
PMID:18251977
  Authors
Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ
  Title
Viral hepatocarcinogenesis: from infection to cancer.
  Journal
Liver Int 28:175-88 (2008)
DOI:10.1111/j.1478-3231.2007.01652.x
Reference
PMID:17059849
  Authors
Chami M, Oules B, Paterlini-Brechot P
  Title
Cytobiological consequences of calcium-signaling alterations induced by human viral proteins.
  Journal
Biochim Biophys Acta 1763:1344-62 (2006)
DOI:10.1016/j.bbamcr.2006.09.025
Reference
PMID:11743185
  Authors
Ganem D
  Title
Virology. The X files--one step closer to closure.
  Journal
Science 294:2299-300 (2001)
DOI:10.1126/science.1067850
Reference
PMID:15132991
  Authors
Chung TW, Lee YC, Kim CH
  Title
Hepatitis B viral HBx induces matrix metalloproteinase-9 gene expression through activation of ERK and PI-3K/AKT pathways: involvement of invasive potential.
  Journal
FASEB J 18:1123-5 (2004)
DOI:10.1096/fj.03-1429fje
Reference
PMID:18605975
  Authors
Gurtsevitch VE
  Title
Human oncogenic viruses: hepatitis B and hepatitis C viruses and their role in hepatocarcinogenesis.
  Journal
Biochemistry (Mosc) 73:504-13 (2008)
DOI:10.1134/S0006297908050039
Reference
PMID:21994545
  Authors
Schadler S, Hildt E
  Title
HBV life cycle: entry and morphogenesis.
  Journal
Viruses 1:185-209 (2009)
DOI:10.3390/v1020185
Reference
PMID:28862649
  Authors
Ortega-Prieto AM, Dorner M
  Title
Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection.
  Journal
Vaccines (Basel) 5:24 (2017)
DOI:10.3390/vaccines5030024
Reference
PMID:28704708
  Authors
Nosratabadi R, Alavian SM, Zare-Bidaki M, Shahrokhi VM, Arababadi MK
  Title
Innate immunity related pathogen recognition receptors and chronic hepatitis B infection.
  Journal
Mol Immunol 90:64-73 (2017)
DOI:10.1016/j.molimm.2017.07.002
Reference
PMID:24530748
  Authors
Bagheri V, Askari A, Arababadi MK, Kennedy D
  Title
Can Toll-Like Receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection?
  Journal
Hum Immunol 75:549-54 (2014)
DOI:10.1016/j.humimm.2014.02.018
Reference
PMID:25550115
  Authors
Zhang E, Lu M
  Title
Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection.
  Journal
Med Microbiol Immunol 204:11-20 (2015)
DOI:10.1007/s00430-014-0370-1
Reference
PMID:20375222
  Authors
Yu S, Chen J, Wu M, Chen H, Kato N, Yuan Z
  Title
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.
  Journal
J Gen Virol 91:2080-90 (2010)
DOI:10.1099/vir.0.020552-0
Reference
PMID:23363957
  Authors
Revill P, Yuan Z
  Title
New insights into how HBV manipulates the innate immune response to establish acute and persistent infection.
  Journal
Antivir Ther 18:1-15 (2013)
DOI:10.3851/IMP2542
Reference
PMID:28893934
  Authors
Hopcraft SE, Damania B
  Title
Tumour viruses and innate immunity.
  Journal
Philos Trans R Soc Lond B Biol Sci 372:20160267 (2017)
DOI:10.1098/rstb.2016.0267
Reference
PMID:22504921
  Authors
Dandri M, Locarnini S
  Title
New insight in the pathobiology of hepatitis B virus infection.
  Journal
Gut 61 Suppl 1:i6-17 (2012)
DOI:10.1136/gutjnl-2012-302056
Related
pathway
hsa04010  MAPK signaling pathway
hsa04064  NF-kappa B signaling pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04210  Apoptosis
hsa04620  Toll-like receptor signaling pathway
hsa04622  RIG-I-like receptor signaling pathway
hsa04630  JAK-STAT signaling pathway
KO pathway
ko05161   

  All links  
No link information was found.
KEGG   PATHWAY: hsa05161
Entry
hsa05161                    Pathway                                
Name
Hepatitis B - Homo sapiens (human)
Description
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.
Class
Human Diseases; Infectious disease: viral
Pathway map
hsa05161  Hepatitis B
hsa05161

Network
nt06162  Hepatitis B virus (HBV)
nt06214  PI3K signaling (cancer)
nt06263  Hepatocellular carcinoma
nt06507  TGFB signaling
nt06517  TLR signaling
nt06518  JAK-STAT signaling
nt06519  RLR signaling
nt06524  Apoptosis
  Element
N00267  HBV HBx to PI3K signaling pathway
N00268  HBV HBx to RIG-I-like receptor signaling pathway
N00531  HBV HBx to TGF-beta signaling pathway
N00532  HBV HBx to Egr-mediated transcription
N00533  HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00534  HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00535  HBV HBx to p53-mediated transcription
N00537  HBV HBx to cell cycle G1/S
N00539  HBV HBx to Ca2+-PYK2-RAS-ERK signaling pathway
N00540  HBV HBx to RAS-ERK signaling pathway
N00541  HBV HBx to RAS-ERK signaling pathway
N00543  HBV HBx to JNK signaling pathway
N00544  HBV HBx to CREB-mediated transcription
N00545  HBV HBx to ERK signaling pathway
N00547  HBV LHBs to PKC-ERK signaling pathway
N00548  HBV HBx to Jak-STAT signaling pathway
N00551  HBV HBs to TLR2/4-MAPK signaling pathway
N00552  HBV pol to TLR3-IRF3 signaling pathway
N00554  HBV HBe to TLR4-IRF3/7 signaling pathway
N00556  HBV HBe to TLR2/4-NFKB signaling pathway
N00558  HBV pol to IFN signaling pathway
Disease
H00412  Hepatitis B; Hepatitis B virus (HBV) infection
Drug
D02745  Interferon alfa-2b (USAN)
D02747  Peginterferon alfa-2a (USAN/INN)
D03305  Interferon alfa (NAMALWA) (JP19)
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; RAC-gamma serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
100506742  CASP12; inactive caspase-12 [KO:K04741] [EC:3.4.22.-]
1017  CDK2; cyclin-dependent kinase 2 isoform 1 [KO:K02206] [EC:2.7.11.22]
1026  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform 1 [KO:K06625]
10454  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform alpha [KO:K04403]
10488  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
10971  YWHAQ; 14-3-3 protein theta [KO:K16197]
110117499  P3R3URF-PIK3R3; LOC110117498-PIK3R3 readthrough [KO:K02649]
114609  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform a [KO:K05403]
1147  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467] [EC:2.7.11.10]
1385  CREB1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
1386  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform 1 [KO:K04450]
1387  CREBBP; CREB-binding protein isoform a [KO:K04498] [EC:2.3.1.48]
1388  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform a [KO:K09049]
1432  MAPK14; mitogen-activated protein kinase 14 isoform 2 [KO:K04441] [EC:2.7.11.24]
148022  TICAM1; TIR domain-containing adapter molecule 1 isoform 1 [KO:K05842]
148327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
1642  DDB1; DNA damage-binding protein 1 [KO:K10610]
1643  DDB2; DNA damage-binding protein 2 isoform WT [KO:K10140]
1654  DDX3X; ATP-dependent RNA helicase DDX3X isoform 1 [KO:K11594] [EC:5.6.2.7]
1869  E2F1; transcription factor E2F1 [KO:K17454]
1870  E2F2; transcription factor E2F2 [KO:K09389]
1871  E2F3; transcription factor E2F3 isoform 1 [KO:K06620]
1959  EGR2; E3 SUMO-protein ligase EGR2 isoform a [KO:K12496]
1960  EGR3; early growth response protein 3 isoform 1 [KO:K12497]
2002  ELK1; ETS domain-containing protein Elk-1 isoform a [KO:K04375]
2033  EP300; histone acetyltransferase p300 isoform 1 [KO:K04498] [EC:2.3.1.48]
207  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
208  AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
2185  PTK2B; protein-tyrosine kinase 2-beta isoform a [KO:K05871] [EC:2.7.10.2]
23118  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform a [KO:K04404]
2353  FOS; protein c-Fos [KO:K04379]
23586  RIGI; antiviral innate immune response receptor RIG-I isoform 1 [KO:K12646] [EC:5.6.2.6]
2885  GRB2; growth factor receptor-bound protein 2 isoform 1 [KO:K04364]
29110  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
317  APAF1; apoptotic protease-activating factor 1 isoform c [KO:K02084]
3265  HRAS; GTPase HRas isoform 1 [KO:K02833]
332  BIRC5; baculoviral IAP repeat-containing protein 5 isoform 2 [KO:K08731]
3339  HSPG2; basement membrane-specific heparan sulfate proteoglycan core protein isoform b precursor [KO:K06255]
3439  IFNA1; interferon alpha-1 precursor [KO:K05414]
3440  IFNA2; interferon alpha-2 precursor [KO:K05414]
3441  IFNA4; interferon alpha-4 precursor [KO:K05414]
3442  IFNA5; interferon alpha-5 precursor [KO:K05414]
3443  IFNA6; interferon alpha-6 precursor [KO:K05414]
3444  IFNA7; interferon alpha-7 precursor [KO:K05414]
3445  IFNA8; interferon alpha-8 precursor [KO:K05414]
3446  IFNA10; interferon alpha-10 precursor [KO:K05414]
3447  IFNA13; interferon alpha-13 precursor [KO:K05414]
3448  IFNA14; interferon alpha-14 precursor [KO:K05414]
3449  IFNA16; interferon alpha-16 precursor [KO:K05414]
3451  IFNA17; interferon alpha-17 precursor [KO:K05414]
3452  IFNA21; interferon alpha-21 precursor [KO:K05414]
3454  IFNAR1; interferon alpha/beta receptor 1 isoform 2 precursor [KO:K05130]
3456  IFNB1; interferon beta precursor [KO:K05415]
353376  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
355  FAS; tumor necrosis factor receptor superfamily member 6 isoform 1 precursor [KO:K04390]
3551  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209] [EC:2.7.11.10]
356  FASLG; tumor necrosis factor ligand superfamily member 6 isoform 1 [KO:K04389]
3569  IL6; interleukin-6 isoform 1 precursor [KO:K05405]
3576  CXCL8; interleukin-8 isoform 1 precursor [KO:K10030]
3654  IRAK1; interleukin-1 receptor-associated kinase 1 isoform 1 [KO:K04730] [EC:2.7.11.1]
3661  IRF3; interferon regulatory factor 3 isoform 1 [KO:K05411]
3665  IRF7; interferon regulatory factor 7 isoform a [KO:K09447]
369  ARAF; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
3716  JAK1; tyrosine-protein kinase JAK1 isoform 1 [KO:K11217] [EC:2.7.10.2]
3717  JAK2; tyrosine-protein kinase JAK2 isoform a [KO:K04447] [EC:2.7.10.2]
3718  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
3725  JUN; transcription factor Jun [KO:K04448]
3845  KRAS; GTPase KRas isoform a [KO:K07827]
4088  SMAD3; mothers against decapentaplegic homolog 3 isoform 1 [KO:K23605]
4089  SMAD4; mothers against decapentaplegic homolog 4 isoform a [KO:K04501]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
4318  MMP9; matrix metalloproteinase-9 preproprotein [KO:K01403] [EC:3.4.24.35]
4609  MYC; myc proto-oncogene protein isoform 1 [KO:K04377]
4615  MYD88; myeloid differentiation primary response protein MyD88 isoform 2 [KO:K04729]
468  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
4772  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform F [KO:K04446]
4773  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332]
4775  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform 1 [KO:K17333]
4776  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform 2 [KO:K17334]
4790  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580]
4792  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
4893  NRAS; GTPase NRas [KO:K07828]
5111  PCNA; proliferating cell nuclear antigen [KO:K04802]
51135  IRAK4; interleukin-1 receptor-associated kinase 4 isoform a [KO:K04733] [EC:2.7.11.1]
5290  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649]
5296  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
537  ATP6AP1; V-type proton ATPase subunit S1 precursor [KO:K03662]
54205  CYCS; cytochrome c [KO:K08738]
5578  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta type isoform 1 [KO:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma type isoform 2 [KO:K19663] [EC:2.7.11.13]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 isoform 1 [KO:K04371] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
5604  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369] [EC:2.7.12.2]
5606  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform B [KO:K04432] [EC:2.7.12.2]
5608  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform 1 [KO:K04433] [EC:2.7.12.2]
5609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform 3 [KO:K04431] [EC:2.7.12.2]
572  BAD; bcl2-associated agonist of cell death [KO:K02158]
57506  MAVS; mitochondrial antiviral-signaling protein isoform 1 [KO:K12648]
581  BAX; apoptosis regulator BAX isoform alpha [KO:K02159]
5894  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366] [EC:2.7.11.1]
5925  RB1; retinoblastoma-associated protein isoform 1 [KO:K06618]
596  BCL2; apoptosis regulator Bcl-2 isoform alpha [KO:K02161]
5970  RELA; transcription factor p65 isoform 1 [KO:K04735]
6300  MAPK12; mitogen-activated protein kinase 12 isoform 1 [KO:K04441] [EC:2.7.11.24]
637  BID; BH3-interacting domain death agonist isoform 2 [KO:K04726]
64135  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
6416  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform 1 [KO:K04430] [EC:2.7.12.2]
64764  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform 1 [KO:K09048]
6554  SLC10A1; hepatic sodium/bile acid cotransporter [KO:K14341]
6654  SOS1; son of sevenless homolog 1 isoform 1 [KO:K03099]
6655  SOS2; son of sevenless homolog 2 isoform 1 [KO:K03099]
6714  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
673  BRAF; serine/threonine-protein kinase B-raf isoform 1 [KO:K04365] [EC:2.7.11.1]
6772  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform alpha [KO:K11220]
6773  STAT2; signal transducer and activator of transcription 2 isoform 1 [KO:K11221]
6774  STAT3; signal transducer and activator of transcription 3 isoform 1 [KO:K04692]
6775  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
6776  STAT5A; signal transducer and activator of transcription 5A isoform 1 [KO:K11223]
6777  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
6778  STAT6; signal transducer and activator of transcription 6 isoform 1 [KO:K11225]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform B [KO:K04427] [EC:2.7.11.25]
7040  TGFB1; transforming growth factor beta-1 proprotein preproprotein [KO:K13375]
7042  TGFB2; transforming growth factor beta-2 proprotein isoform 2 preproprotein [KO:K13376]
7043  TGFB3; transforming growth factor beta-3 proprotein isoform 1 preproprotein [KO:K13377]
7046  TGFBR1; TGF-beta receptor type-1 isoform 1 precursor [KO:K04674] [EC:2.7.11.30]
7048  TGFBR2; TGF-beta receptor type-2 isoform B precursor [KO:K04388] [EC:2.7.11.30]
7097  TLR2; toll-like receptor 2 precursor [KO:K10159]
7098  TLR3; toll-like receptor 3 precursor [KO:K05401]
7099  TLR4; toll-like receptor 4 isoform A precursor [KO:K10160]
7124  TNF; tumor necrosis factor [KO:K03156]
7157  TP53; cellular tumor antigen p53 isoform a [KO:K04451]
7187  TRAF3; TNF receptor-associated factor 3 isoform 1 [KO:K03174]
7189  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
7297  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform 2 [KO:K11219] [EC:2.7.10.2]
7419  VDAC3; non-selective voltage-gated ion channel VDAC3 isoform 1 [KO:K15041]
7529  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
7534  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
836  CASP3; caspase-3 isoform a preproprotein [KO:K02187] [EC:3.4.22.56]
841  CASP8; caspase-8 isoform 2 precursor [KO:K04398] [EC:3.4.22.61]
842  CASP9; caspase-9 isoform alpha precursor [KO:K04399] [EC:3.4.22.62]
843  CASP10; caspase-10 isoform 2 preproprotein [KO:K04400] [EC:3.4.22.63]
84699  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform a [KO:K09048]
8503  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649]
8517  IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210]
8772  FADD; FAS-associated death domain protein [KO:K02373]
890  CCNA2; cyclin-A2 [KO:K06627]
8900  CCNA1; cyclin-A1 [KO:K06627]
898  CCNE1; G1/S-specific cyclin-E1 isoform 1 [KO:K06626]
90993  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform 1 [KO:K09048]
9134  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
9586  CREB5; cyclic AMP-responsive element-binding protein 5 isoform alpha [KO:K09047]
9641  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 1 [KO:K07211] [EC:2.7.11.10]
Compound
C00076  Calcium cation
Reference
PMID:30059722
  Authors
Caballero A, Tabernero D, Buti M, Rodriguez-Frias F
  Title
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
  Journal
Antiviral Res 158:34-44 (2018)
DOI:10.1016/j.antiviral.2018.07.019
Reference
PMID:22869468
  Authors
Walsh R, Locarnini S
  Title
Hepatitis B precore protein: pathogenic potential and therapeutic promise.
  Journal
Yonsei Med J 53:875-85 (2012)
DOI:10.3349/ymj.2012.53.5.875
Reference
PMID:26239691
  Authors
Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS
  Title
Present and future therapies of hepatitis B: From discovery to cure.
  Journal
Hepatology 62:1893-908 (2015)
DOI:10.1002/hep.28025
Reference
PMID:26776362
  Authors
Morikawa K, Suda G, Sakamoto N
  Title
Viral life cycle of hepatitis B virus: Host factors and druggable targets.
  Journal
Hepatol Res 46:871-7 (2016)
DOI:10.1111/hepr.12650
Reference
PMID:19201080
  Authors
Feitelson MA, Reis HM, Tufan NL, Sun B, Pan J, Lian Z
  Title
Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease.
  Journal
Cancer Lett 286:69-79 (2009)
DOI:10.1016/j.canlet.2008.12.010
Reference
PMID:19263472
  Authors
Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, Kobayashi K, Yokote K, Koike K, Okazaki K
  Title
Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.
  Journal
Hepatology 49:1203-17 (2009)
DOI:10.1002/hep.22765
Reference
PMID:15173177
  Authors
Yoo YG, Lee MO
  Title
Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor.
  Journal
J Biol Chem 279:36242-9 (2004)
DOI:10.1074/jbc.M401290200
Reference
PMID:16459163
  Authors
Zhang X, Zhang H, Ye L
  Title
Effects of hepatitis B virus X protein on the development of liver cancer.
  Journal
J Lab Clin Med 147:58-66 (2006)
DOI:10.1016/j.lab.2005.10.003
Reference
PMID:19854353
  Authors
Benhenda S, Cougot D, Buendia MA, Neuveut C
  Title
Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.
  Journal
Adv Cancer Res 103:75-109 (2009)
DOI:10.1016/S0065-230X(09)03004-8
Reference
PMID:21994562
  Authors
Benhenda S, Cougot D, Neuveut C, Buendia MA
  Title
Liver cell transformation in chronic HBV infection.
  Journal
Viruses 1:630-46 (2009)
DOI:10.3390/v1030630
Reference
PMID:11099494
  Authors
Diao J, Khine AA, Sarangi F, Hsu E, Iorio C, Tibbles LA, Woodgett JR, Penninger J, Richardson CD
  Title
X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.
  Journal
J Biol Chem 276:8328-40 (2001)
DOI:10.1074/jbc.M006026200
Reference
PMID:16891440
  Authors
Park NH, Song IH, Chung YH
  Title
Chronic hepatitis B in hepatocarcinogenesis.
  Journal
Postgrad Med J 82:507-15 (2006)
DOI:10.1136/pgmj.2006.047431
Reference
PMID:28820498
  Authors
Lin S, Zhang YJ
  Title
Interference of Apoptosis by Hepatitis B Virus.
  Journal
Viruses 9:230 (2017)
DOI:10.3390/v9080230
Reference
PMID:16173017
  Authors
Zhang X, Dong N, Yin L, Cai N, Ma H, You J, Zhang H, Wang H, He R, Ye L
  Title
Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues.
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Related
pathway
hsa04010  MAPK signaling pathway
hsa04064  NF-kappa B signaling pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04210  Apoptosis
hsa04620  Toll-like receptor signaling pathway
hsa04622  RIG-I-like receptor signaling pathway
hsa04630  JAK-STAT signaling pathway
KO pathway
ko05161   

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