Hepatitis B infection (WP4666)

Homo sapiens

The Hepatitis B virus (HBV) is a virus in the Hepadnaviridae family which infects hepatocytes in the liver. It causes both acute and chronic infections, and prolonged chronic infection can lead to complications such as cirrhosis and an increased risk of hepatocellular carcinoma (HCC). The left side of the pathway describes the pathogenesis of HBV. The virus binds NTCP (SLC10A1) and is subsequently endocytosed. It is transported to the nucleus where viral polymerase creates covalently closed circular DNA (cccDNA). Using the host RNA polymerase, this is transcribed into viral mRNAs. Viral DNA polymerase then synthesizes viral DNA via its reverse transcriptase activity. Assembled viral particles exit the cell via the ESCRT pathway. The HBV regulatory protein HBx interferes with many cellular processes including transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability. This pathway was developed based on https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa05161. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org

Authors

Kristina Hanspers , Finterly Hu , and Egon Willighagen

Activity

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Organisms

Homo sapiens

Communities

CPTAC Diseases

Annotations

Cell Type Ontology

hepatocyte

Disease Ontology

hepatitis B

Participants

Label Type Compact URI Comment
Ca2+ Metabolite chebi:29108
Ca2+ Metabolite chebi:29108
Ca2+ Metabolite chebi:29108
TGFB1 GeneProduct ensembl:ENSG00000105329
ATP6AP1 GeneProduct ensembl:ENSG00000071553
MMP9 GeneProduct ensembl:ENSG00000100985
JAK1 GeneProduct ensembl:ENSG00000162434
CREB3 GeneProduct ensembl:ENSG00000107175
NFATC1 GeneProduct ensembl:ENSG00000131196
MAP2K3 GeneProduct ensembl:ENSG00000034152
CDKN1A GeneProduct ensembl:ENSG00000124762
ATF2 GeneProduct ensembl:ENSG00000115966
MYD88 GeneProduct ensembl:ENSG00000172936
MAPK11 GeneProduct ensembl:ENSG00000185386
TNF GeneProduct ensembl:ENSG00000232810
HSPG2 GeneProduct ensembl:ENSG00000142798
DDB1 GeneProduct ensembl:ENSG00000167986
MAP3K1 GeneProduct ensembl:ENSG00000095015
ARAF GeneProduct ensembl:ENSG00000078061
FASLG GeneProduct ensembl:ENSG00000117560
EGR2 GeneProduct ensembl:ENSG00000122877
SLC10A1 GeneProduct ensembl:ENSG00000100652
TGFB2 GeneProduct ensembl:ENSG00000092969
TGFB3 GeneProduct ensembl:ENSG00000119699
TGFBR1 GeneProduct ensembl:ENSG00000106799
TGFBR2 GeneProduct ensembl:ENSG00000163513
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
MYC GeneProduct ensembl:ENSG00000136997
DDB2 GeneProduct ensembl:ENSG00000134574
EGR3 GeneProduct ensembl:ENSG00000179388
CREBBP GeneProduct ensembl:ENSG00000005339
EP300 GeneProduct ensembl:ENSG00000100393
PIK3CA GeneProduct ensembl:ENSG00000121879 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18706
PIK3R1 GeneProduct ensembl:ENSG00000145675 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18708
PIK3R2 GeneProduct ensembl:ENSG00000105647 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709
PIK3CB GeneProduct ensembl:ENSG00000051382 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:74769
PIK3CD GeneProduct ensembl:ENSG00000171608 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707
PIK3R3 GeneProduct ensembl:ENSG00000117461 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:75669
AKT1 GeneProduct ensembl:ENSG00000142208 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11651
AKT3 GeneProduct ensembl:ENSG00000117020 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23797
AKT2 GeneProduct ensembl:ENSG00000105221 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11652
IKBKB GeneProduct ensembl:ENSG00000104365 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16150
IKBKG GeneProduct ensembl:ENSG00000269335 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16151
CHUK GeneProduct ensembl:ENSG00000213341 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16151
BAD GeneProduct ensembl:ENSG00000002330 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12015
NFKB1 GeneProduct ncbigene:4790
RELA GeneProduct ensembl:ENSG00000173039
BCL2 GeneProduct ensembl:ENSG00000171791
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
MAP2K4 GeneProduct ensembl:ENSG00000065559
YWHAQ GeneProduct ensembl:ENSG00000134308
YWHAB GeneProduct ensembl:ENSG00000166913
YWHAZ GeneProduct ensembl:ENSG00000164924
FASLG GeneProduct ensembl:ENSG00000117560
FAS GeneProduct ensembl:ENSG00000026103
FADD GeneProduct ensembl:ENSG00000168040
CASP8 GeneProduct ensembl:ENSG00000064012
CASP10 GeneProduct ensembl:ENSG00000003400
BID GeneProduct ensembl:ENSG00000015475
BCL2 GeneProduct ensembl:ENSG00000171791
BAX GeneProduct ensembl:ENSG00000087088
CASP3 GeneProduct ensembl:ENSG00000164305
CASP12 GeneProduct ensembl:ENSG00000204403
CYCS GeneProduct ensembl:ENSG00000172115
APAF1 GeneProduct ensembl:ENSG00000120868
CASP9 GeneProduct ensembl:ENSG00000132906
BIRC5 GeneProduct ensembl:ENSG00000089685
PRKCA GeneProduct ensembl:ENSG00000154229
PRKCB GeneProduct ensembl:ENSG00000166501
PRKCG GeneProduct ensembl:ENSG00000126583
NFATC2 GeneProduct ensembl:ENSG00000101096
NFATC3 GeneProduct ensembl:ENSG00000072736
NFATC4 GeneProduct ensembl:ENSG00000100968
JAK2 GeneProduct ensembl:ENSG00000096968
JAK3 GeneProduct ensembl:ENSG00000105639
TYK2 GeneProduct ensembl:ENSG00000105397
STAT3 GeneProduct ensembl:ENSG00000168610
STAT1 GeneProduct ensembl:ENSG00000115415
STAT2 GeneProduct ensembl:ENSG00000170581
STAT4 GeneProduct ensembl:ENSG00000138378
STAT5A GeneProduct ensembl:ENSG00000126561
STAT5B GeneProduct ensembl:ENSG00000173757
STAT6 GeneProduct hgnc.symbol:STAT6
VDAC3 GeneProduct ensembl:ENSG00000078668
PTK2B GeneProduct ensembl:ENSG00000120899
SRC GeneProduct ensembl:ENSG00000197122
GRB2 GeneProduct ensembl:ENSG00000177885
SOS1 GeneProduct ensembl:ENSG00000115904
SOS2 GeneProduct ensembl:ENSG00000100485
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703
NRAS GeneProduct ensembl:ENSG00000213281
PRKCA GeneProduct ensembl:ENSG00000154229
PRKCB GeneProduct ensembl:ENSG00000166501
PRKCG GeneProduct ensembl:ENSG00000126583
RAF1 GeneProduct ensembl:ENSG00000132155
BRAF GeneProduct ensembl:ENSG00000157764
MAP3K1 GeneProduct ensembl:ENSG00000095015
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
MAP2K1 GeneProduct ncbigene:5604
MAPK1 GeneProduct ncbigene:5594
MAPK3 GeneProduct ncbigene:5595
MAP2K2 GeneProduct ncbigene:5605
CREBBP GeneProduct ensembl:ENSG00000005339
EP300 GeneProduct ensembl:ENSG00000100393
JUN GeneProduct ensembl:ENSG00000177606
SMAD4 GeneProduct ensembl:ENSG00000141646
STAT3 GeneProduct ensembl:ENSG00000168610
ELK1 GeneProduct ensembl:ENSG00000126767
FOS GeneProduct ensembl:ENSG00000170345
JUN GeneProduct ensembl:ENSG00000177606
MYC GeneProduct ensembl:ENSG00000136997
CREB1 GeneProduct ensembl:ENSG00000118260
ATF4 GeneProduct ensembl:ENSG00000128272
ATF6B GeneProduct ensembl:ENSG00000213676
CREB5 GeneProduct ensembl:ENSG00000146592
CREB3L2 GeneProduct ensembl:ENSG00000182158
CREB3L4 GeneProduct ensembl:ENSG00000143578
CREB3L1 GeneProduct ensembl:ENSG00000157613
CREB3L3 GeneProduct ensembl:ENSG00000060566
PCNA GeneProduct ensembl:ENSG00000132646
CXCL8 GeneProduct ensembl:ENSG00000169429
MMP9 GeneProduct ensembl:ENSG00000100985
TLR2 GeneProduct ensembl:ENSG00000137462
TLR4 GeneProduct ensembl:ENSG00000136869
IFNAR1 GeneProduct ensembl:ENSG00000142166
TIRAP GeneProduct ensembl:ENSG00000150455
MYD88 GeneProduct ensembl:ENSG00000172936
TIRAP GeneProduct ensembl:ENSG00000150455
IRAK1 GeneProduct ensembl:ENSG00000184216
IRAK4 GeneProduct ensembl:ENSG00000198001
TICAM2 GeneProduct ensembl:ENSG00000243414
TRAF6 GeneProduct ensembl:ENSG00000175104
TAB1 GeneProduct ensembl:ENSG00000100324
TAB2 GeneProduct ensembl:ENSG00000055208
MAP3K7 GeneProduct ensembl:ENSG00000135341
IKBKB GeneProduct ensembl:ENSG00000104365 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16150
IKBKG GeneProduct ensembl:ENSG00000269335 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16151
CHUK GeneProduct ensembl:ENSG00000213341 SOS1; son of sevenless homolog 1 (Drosophila)
Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16151
NFKB1 GeneProduct ncbigene:4790
RELA GeneProduct ensembl:ENSG00000173039
JUN GeneProduct ensembl:ENSG00000177606
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
MAP2K1 GeneProduct ncbigene:5604
MAPK1 GeneProduct ncbigene:5594
MAPK3 GeneProduct ncbigene:5595
MAP2K2 GeneProduct ncbigene:5605
MAP2K6 GeneProduct ensembl:ENSG00000108984
TNF GeneProduct ensembl:ENSG00000232810
IL6 GeneProduct ensembl:ENSG00000136244
MAPK12 GeneProduct ensembl:ENSG00000188130
MAPK13 GeneProduct ensembl:ENSG00000156711
MAPK14 GeneProduct ensembl:ENSG00000112062
MAP2K4 GeneProduct ensembl:ENSG00000065559
MAP2K7 GeneProduct ensembl:ENSG00000076984
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
TLR3 GeneProduct ensembl:ENSG00000164342
TICAM1 GeneProduct ensembl:ENSG00000127666
TRAF3 GeneProduct ensembl:ENSG00000131323
IKBKE GeneProduct ensembl:ENSG00000263528
TBK1 GeneProduct ensembl:ENSG00000183735
DDX3X GeneProduct ensembl:ENSG00000215301
IRF3 GeneProduct ensembl:ENSG00000126456
IRF7 GeneProduct ensembl:ENSG00000185507
STAT1 GeneProduct ensembl:ENSG00000115415
STAT2 GeneProduct ensembl:ENSG00000170581
MYD88 GeneProduct ensembl:ENSG00000172936
DDX58 GeneProduct ensembl:ENSG00000107201
IFIH1 GeneProduct ensembl:ENSG00000115267
MAVS GeneProduct ensembl:ENSG00000088888
IFNA1 GeneProduct ncbigene:3439
IFNA7 GeneProduct ncbigene:3444
IFNA5 GeneProduct ncbigene:3442
IFNA6 GeneProduct ncbigene:3443
IFNA4 GeneProduct ncbigene:3441
IFNA2 GeneProduct ncbigene:3440
IFNA8 GeneProduct ncbigene:3445
IFNA10 GeneProduct ncbigene:3446
IFNA13 GeneProduct ncbigene:3447
IFNA14 GeneProduct ncbigene:3448
IFNA16 GeneProduct ncbigene:3449
IFNA17 GeneProduct ncbigene:3451
IFNA21 GeneProduct ncbigene:3452
IFNA1 GeneProduct ncbigene:3439
IFNA7 GeneProduct ncbigene:3444
IFNA5 GeneProduct ncbigene:3442
IFNA6 GeneProduct ncbigene:3443
IFNA4 GeneProduct ncbigene:3441
IFNA2 GeneProduct ncbigene:3440
IFNA8 GeneProduct ncbigene:3445
IFNA10 GeneProduct ncbigene:3446
IFNA13 GeneProduct ncbigene:3447
IFNA14 GeneProduct ncbigene:3448
IFNA16 GeneProduct ncbigene:3449
IFNA17 GeneProduct ncbigene:3451
IFNA21 GeneProduct ncbigene:3452
IFNB1 GeneProduct ensembl:ENSG00000171855

References

  1. KEGG Pathway: hsa05161
  2. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
  3. Hepatitis B virus molecular biology and pathogenesis. Lamontagne RJ, Bagga S, Bouchard MJ. Hepatoma Res. 2016;2:163–86. PubMed Europe PMC Scholia