TABLE 2.
HBx interacting proteins listed together with the cellular processes or pathways in which they are involved.
| Interaction partner | Cellular Process | References |
| RPB5 | Transcriptional machinery | Cheong et al., 1995 |
| TFIIB | Transcriptional machinery | Lin et al., 1997 |
| TBP | Transcriptional machinery | Qadri et al., 1995 |
| TFIIH | Transcriptional machinery | Qadri et al., 2011 |
| CBP | Coactivator | Cougot et al., 2007 |
| P300 | Coactivator | Cougot et al., 2007 |
| PCAF | Coactivator | Chan et al., 2013 |
| ATF/CREB | Transcription factor | Maguire et al., 1991 |
| ATF3 | Transcription factor | Barnabas and Andrisani, 2000 |
| ICERIIgamma | Transcription factor | Barnabas et al., 1997; Barnabas and Andrisani, 2000 |
| gadd153/Chop10 | Transcription factor | Barnabas et al., 1997 |
| c/EBPA | Transcription factor | Choi et al., 1999 |
| NF-IL-6 | Transcription factor | Barnabas et al., 1997 |
| ETS/ERG# | Transcription factor | Qin et al., 2013 |
| EGR/EGRF1 | Transcription factor | Yoo and Lee, 2004 |
| SMAD4 | Transcription factor | Shi et al., 2016 |
| Oct1 | Transcription factor | Antunovic et al., 1993 |
| RXR | Transcription factor | Kong et al., 2000 |
| P53 | Transcription factor. Induces destabilization of HBx. | Belloni et al., 2009; Xian et al., 2010; Iyer and Groopman, 2011 |
| PRMT1 | Relieves PRMT1 suppression from viral replication. | Benhenda et al., 2013 |
| Spindlin1 | Interaction with HBx relieves repression by Spindlin1. Knockdown induced an increase in HBV transcription and H3H4 trimethylation on the cccDNA. | Ducroux et al., 2014 |
| PP1 | HBx interferes with the inactivation of CREB/CREB1 by PP1. | Cougot et al., 2012 |
| JMJD5 | Interaction with HBx facilitates HBV replication through the hydroxylase activity of JMJD5. | Kouwaki et al., 2016 |
| DDB1 | Recruited resulting in SMC5/6 degradation. | Decorsiere et al., 2016 |
| SMC5/6 | Recruited to the ubiquitin machinery to be degraded to enhance transcription. | Decorsiere et al., 2016 |
| hepatocystin | May be an antiviral pathway, hepatocystin seems to accelerate HBx degradation. | Shin et al., 2013 |
| Clathrin heavy chain | Unknown | Shin et al., 2013 |
| HSPA5 | Unknown | Shin et al., 2013 |
| HSPA9 | Unknown | Shin et al., 2013 |
| CALD1 | Unknown | Shin et al., 2013 |
| HSPA8 | Unknown | Shin et al., 2013 |
| XRCC6 | Unknown | Shin et al., 2013 |
| PDIA4 | Unknown | Shin et al., 2013 |
| PRKCSH | Unknown | Shin et al., 2013 |
| HSPA6 | Unknown | Shin et al., 2013 |
| DDX17 | Unknown | Shin et al., 2013 |
| HSPA1L | Unknown | Shin et al., 2013 |
| HSPA1A | Unknown | Shin et al., 2013 |
| SIRT1 | SIRT1 interacts with HBx thereby enabling HBx-induced transcriptional activity cccDNA. | Srisuttee et al., 2012; Deng et al., 2017 |
| Set1A/SETD1A# | Recruited by HBx to cccDNA to increase transcription. | Alarcon et al., 2016 |
| LSD1# | Bound to viral promotors. | Alarcon et al., 2016 |
| CRTC1 | Interaction associated with increased transcription. | Tang et al., 2014 |
| CPAP/CENPJ | Promotes HBx-mediated cell proliferation and migration in a SUMO-dependent manner. | Yang et al., 2013 |
| CREB/CREB1 | Upregulated via HBx-CREB/CREB1 interaction. | Yang et al., 2013 |
| CRM1/XPO1 | Potential activation of CRM1/XPO1 and role in HBx-mediated carcinogenesis. | Forgues et al., 2001 |
| NFκB# | Relocalization via NES motif. | Forgues et al., 2001 |
| VISA/MAVs | Disruption of VISA/MAVs and downstream interacting proteins thereby impairing IFN signaling. | Wang X. et al., 2010 |
| MDA5 | Impairment of IFN signaling. | Wang X. et al., 2010 |
| GRP78 | Role in HCC via suppression of eIF2α phosphorylation, inhibited expression of ATF4/CHOP/Bcl-2, and reduced cleavage of PARP. | Li et al., 2017 |
| AKT1 | Cell proliferation, abrogation of apoptosis and tumorigenic transformation of cells. | Khattar et al., 2012 |
| Bcl-2 | Management of calcium levels to benefit viral replication. | Geng et al., 2012 |
| BCL2L1 | Management of calcium levels to benefit viral replication. | Geng et al., 2012 |
| HDAC1 | Repression insulin-like growth factor binding protein-3. HBx also induces HDAC1. | Pollicino et al., 2006; Yoo et al., 2008; Shon et al., 2009 |
| SP1# | HBx induces deacetylation of SP1. | Pollicino et al., 2006; Yoo et al., 2008; Shon et al., 2009 |
| HIF1a | HBx aids the MTA1/HDAC complex in stabilizing HIF1a. | Yoo et al., 2008 |
| USP-15 | USP-15 mediated deubiquitylation protects HBx from proteasomal degradation. | Su et al., 2017 |
| PARP1 | DNA damage and repair, carcinogenesis. | Na et al., 2016 |
| Cardiolipin (lipid) | Mitochondrial membrane permeabilization. | You et al., 2019 |
| Prdx1 | Peroxiredoxin interfaces with HBV-RNA to promote RNA decay, potentially HBx rescues this event. | Deng et al., 2018, 2019 |
| Parvulin 14/PIN4 | Interaction with HBx in nucleus, cytoplasm and mitochondria to enhance HBx stability, translocation to the nucleus and mitochondria to increase HBV replication. | Saeed et al., 2018 |
| Parvulin 17 | Interaction with HBx in nucleus, cytoplasm and mitochondria to enhance HBx stability, translocation to the nucleus and mitochondria to increase HBV replication. | Saeed et al., 2018 |
| 14-3-3ζ | Interaction found in HCC cells, involvement of AKT pathway. | Tang et al., 2018 |
| c-myc | Oncogenesis | Lee et al., 2016 |
| Orail protein | Calcium metabolism | Yao et al., 2018 |
| HMGB1 | Autophagy | Fu et al., 2018 |
| FXR/NR1H4 | Transactivation FXR/NR1H4, oncogenesis | Niu Y. et al., 2017 |
| PP2Ac/PP2CA | Cell cycle and apoptosis | Gong et al., 2016 |
| SMYD3 | Involved in AP1 activation | Hayashi et al., 2016 |
| P62 | Glucose metabolism | Liu B. et al., 2015 |
| TLR4 | Tumorigenesis | Wang et al., 2015 |
| BST-2@ | HBV restriction factor | Lv et al., 2015 |
| MBD2 | Involved in epigenetics of histones, potentially in HCC. | Liu X.Y. et al., 2015 |
| TRUSS/TRPC4AP | May be linked to pathological sequelae of HBV. | Jamal et al., 2015 |
| MKI67 | Cell proliferation | Zhang et al., 2015 |
| ENPEP | Cell proliferation | Zhang et al., 2015 |
| MIF | Cell proliferation | Zhang et al., 2015 |
| PYY | Cell proliferation | Zhang et al., 2015 |
| NOLC1 | Cell proliferation | Zhang et al., 2015 |
| CDC42 | Cell adhesion | Zhang et al., 2015 |
| IQGAP1 | Cell adhesion | Zhang et al., 2015 |
| LMO7 | Cell adhesion | Zhang et al., 2015 |
| ACTN4 | Cell adhesion | Zhang et al., 2015 |
| CTNNA2 | Cell adhesion | Zhang et al., 2015 |
| MYH2 | Cell adhesion | Zhang et al., 2015 |
| FILAMIN | Cell adhesion | Zhang et al., 2015 |
| ITGB1 | Cell adhesion | Zhang et al., 2015 |
| TLN1 | Cell adhesion | Zhang et al., 2015 |
| NRXN1 | Cell adhesion | Zhang et al., 2015 |
| CDH2 | Cell migration | Zhang et al., 2015 |
| NOTCH4 | Angiogenesis | Zhang et al., 2015 |
| CTNNB1 | Angiogenesis | Zhang et al., 2015 |
| ANXA2 | Angiogenesis | Zhang et al., 2015 |
| ATP5B | Angiogenesis/cell adhesion | Zhang et al., 2015 |
| PSMC4 | Protein degradation | Zhang et al., 2015 |
| PSMB3 | Protein degradation | Zhang et al., 2015 |
| VDAC1 | Anion transport | Zhang et al., 2015 |
| VDAC2 | Anion transport | Zhang et al., 2015 |
| SLC25A3 | Transport | Zhang et al., 2015 |
| S100A9 | Viral reproduction | Zhang et al., 2015 |
| SLC25A5 | Viral reproduction | Zhang et al., 2015 |
| SLC25A10 | Metabolic process | Zhang et al., 2015 |
| SLC20A1 | Signal transduction | Zhang et al., 2015 |
| SLC3A2 | Immune system process | Zhang et al., 2015 |
| RAP1B | Signal transduction | Zhang et al., 2015 |
| RAB10 | Signal transduction | Zhang et al., 2015 |
| RAB11B | Signal transduction | Zhang et al., 2015 |
| RAB5A | Signal transduction | Zhang et al., 2015 |
| FIS1 | Programmed cell death | Zhang et al., 2015 |
| KIF1B | Programmed cell death | Zhang et al., 2015 |
| DAP3 | Induction of apoptosis | Zhang et al., 2015 |
| VIM | Apoptosis | Zhang et al., 2015 |
| JUP | Cell migration | Zhang et al., 2015 |
| RPS7 | Viral reproduction | Zhang et al., 2015 |
| RPS10 | Viral reproduction | Zhang et al., 2015 |
| RPS16 | Viral reproduction | Zhang et al., 2015 |
| RPS20 | Viral reproduction | Zhang et al., 2015 |
| RPL30 | Viral reproduction | Zhang et al., 2015 |
| RPL38 | Viral reproduction | Zhang et al., 2015 |
| BANF1 | Viral reproduction | Zhang et al., 2015 |
| AP1B1 | Viral reproduction | Zhang et al., 2015 |
| BSG | Immune system process | Zhang et al., 2015 |
| ACTR1A | Cell cycle | Zhang et al., 2015 |
| SRSF1 | mRNA processing | Zhang et al., 2015 |
| DDB1 | Wnt receptor signaling pathway | Zhang et al., 2015 |
| ATP5C1 | Oxidative phosphorylation | Zhang et al., 2015 |
| PCMT1 | Protein methylation | Zhang et al., 2015 |
| PPIA | Viral reproduction | Zhang et al., 2015 |
| HIST2H2BE | Nucleosome assembly | Zhang et al., 2015 |
| PCBP1 | Metabolic process | Zhang et al., 2015 |
| GAPDH | Glycolysis | Zhang et al., 2015 |
| HSP90AB1 | Regulation of signaling pathway | Zhang et al., 2015 |
| COXIII@ | Mitochondrial function | Li et al., 2015; Zou et al., 2015 |
| ECSIT | Involved in IL-1β induction of NF-κB activation. | Chen et al., 2015 |
| Skp2 | Cell cycle deregulation and transformation. | Kalra and Kumar, 2006 |
| PSMA7/XAPC7 | Proteasome | Huang et al., 1996 |
| PSMC1 | Proteasome | Zhang et al., 2000 |
| PSMA1 | Proteasome | Hu et al., 1999 |
| PLSCR1 | Unknown | Yuan et al., 2015 |
| GRN | Unknown | Yuan et al., 2015 |
| SPRY1 | Unknown | Yuan et al., 2015 |
| NKD2 | Unknown | Yuan et al., 2015 |
| SYVN1 | Unknown | Yuan et al., 2015 |
| NOTCH3 | Unknown | Yuan et al., 2015 |
| LAMC3 | Unknown | Yuan et al., 2015 |
| SERTAD1 | Unknown | Yuan et al., 2015 |
| GAA | Unknown | Yuan et al., 2015 |
| USP37 | Cell cycle progression | Saxena and Kumar, 2014 |
| E4F1 | P53-dependent growth arrest | Dai Y. et al., 2014 |
| Pregnane X receptor | Potentially involved in carcinogenesis | Niu et al., 2013 |
| apoA-I | HBV secretion | Zhang et al., 2013 |
| hBubR1/BUB1 | Genomic stability | Chae et al., 2013 |
| c-FLIPL | Apoptosis | Kim and Seong, 2003 |
| c-FLIPS | Apoptosis | Kim and Seong, 2003 |
| AIF | Apoptosis | Liu et al., 2012 |
| AMID | Apoptosis | Liu et al., 2012 |
| AIB1 | NFκB signaling | Hong et al., 2012 |
| eEF1A1 | Actin bundling | Lin et al., 2012 |
| VCP | NFκB signaling | Jiao et al., 2011 |
| RPS3a | NFκB signaling | Lim et al., 2011 |
| Gli1 | Hedgehog signaling | Kim et al., 2011 |
| Phosphor-p65 | NFκB signaling | Shukla et al., 2011 |
| IPS-1 | RIGI signaling | Kumar et al., 2011 |
| C/EBPα | Insulin signaling | Kim K. et al., 2010 |
| PTTG1@ | Tumorigenesis | Molina-Jimenez et al., 2010 |
| Cul1@ | Tumorigenesis | Molina-Jimenez et al., 2010 |
| TNFR1@ | NFκB signaling | Kim J.Y. et al., 2010 |
| Cortactin | Cytoskeletal | Feng et al., 2010 |
| Yes1 | Cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. | Feng et al., 2010 |
| CRK-D2 | Regulates cell adhesion, spreading and migration. | Feng et al., 2010 |
| c-Src | Signal transduction | Feng et al., 2010 |
| Y124 | Unknown | Feng et al., 2010 |
| RasGAP | GTPase, unknown | Feng et al., 2010 |
| Abl | Cell growth and survival, cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. | Feng et al., 2010 |
| ITSN-D1/ITSN1 | Unknown | Feng et al., 2010 |
| Abl2 | Cell growth and survival, cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. | Feng et al., 2010 |
| OSF/OSTF1 | Cell adhesion | Feng et al., 2010 |
| Tec | Cytoskeletal, adaptive immunity | Feng et al., 2010 |
| PIG2/GAMT | Carcinogenesis | Feng et al., 2010 |
| ARH6 | DNA damage | Feng et al., 2010 |
| EFS | Cell adhesion | Feng et al., 2010 |
| RHG4 | Unknown | Feng et al., 2010 |
| VINE-D1 | Cytoskeletal | Feng et al., 2010 |
| VINE-D3 | Cytoskeletal | Feng et al., 2010 |
| HSP72/ASPA1A | Chaperone | Wang et al., 2008 |
| C/EBPbeta | Phase II detoxifying pathways. | Cho et al., 2009 |
| DNMT3A | Epigenetic modifications | Zheng et al., 2009 |
| Bax | Apoptosis | Kim H.J. et al., 2008 |
| VBP1 | NFκB signaling | Kim S.Y. et al., 2008 |
| betaPIX | Rec1 signaling | Tan et al., 2008 |
| HBXIP | Centrosome and spindle formation. | Wen et al., 2008 |
| Pin1 | Carcinogenesis | Pang et al., 2007 |
| AR | Gene expression | Zheng et al., 2007 |
| PP2Calpha | Carcinogenesis | Kim et al., 2006 |
| cyclin E/A | Cell cycle regulation | Mukherji et al., 2007 |
| vinexin-beta | Cytoskeletal organization | Tan et al., 2006 |
| MIF | Apoptosis | Zhang et al., 2006 |
| Jab1/cops5 | AP1 signaling | Tanaka et al., 2006 |
| GNbeta5 | Unknown | Lwa and Chen, 2005 |
| p120E4F | Mitosis and cell cycle | Rui et al., 2006 |
| Hepsin | Apoptosis | Zhang et al., 2005 |
| Hsp60 | Apoptosis | Tanaka et al., 2004 |
| PPARgamma | Apoptosis | Choi et al., 2004 |
| ASC-2 | Carcinogenesis | Kong et al., 2003 |
| E2F1 | Carcinogenesis | Choi et al., 2002 |
| NF-AT1/NFATC2 | Calcium metabolism | Carretero et al., 2002 |
| Tbp1 | Transcription | Barak et al., 2001 |
| NF-IL6 | IL6 signaling | Ohno et al., 1999 |
| Jak1 | JAK/STAT signaling | Lee and Yun, 1998 |
| XAP-1/UVDDB/DDB1 | DNA damage repair, carcinogenesis. | Becker et al., 1998 |
| RPB5 | Transcription | Lin et al., 1997 |
| HVDAC3/HDAC3@ | HBx colocalized with HVDAC3/HDAC3 at the mitochondria. | Rahmani et al., 2000 |
| AP2α# | HBx modulates SPHK1 via AP2α. | Lu et al., 2015 |
| SetDB1# | HBx relieves SETDB1-mediated H3K9me3 induced silencing of cccDNA. | Riviere et al., 2015 |
| HP1/CBX1# | HBx relieves HP1/CBX1 induced silencing of cccDNA. | Riviere et al., 2015 |
| Id-1# | Id-1 destabilizes HBx by facilitating the interaction between ubiquitinated HBx and the proteasome. | Ling et al., 2008 |
| HDM2/MDM2# | Promotes NEDDylation of HBx thereby enhancing its stability. | Liu et al., 2017 |
| WDR5 | Facilitates recruitment of HBx to promotor regions. | Gao et al., 2020 |
| CBFβ | Blocks HBx function in promoting replication. | Xu et al., 2019 |
| inhibitors of differentiation 1 (Id1) | Interaction accelerates degradation of these proteins. | Xia et al., 2020 |
| inhibitors of differentiation (Id3) | Interaction accelerates degradation of these proteins. | Xia et al., 2020 |
| PRPF31 | Potential enhancement of cccDNA transcription through this interaction. | Kinoshita et al., 2017 |
# Unknown if this pertains a real protein-protein interaction; @ potential interaction, evidenced by co-localization.