X_HBVCJ
ID X_HBVCJ Reviewed; 154 AA.
AC Q69027;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=Protein X {ECO:0000255|HAMAP-Rule:MF_04074};
DE AltName: Full=HBx {ECO:0000255|HAMAP-Rule:MF_04074};
DE AltName: Full=Peptide X {ECO:0000255|HAMAP-Rule:MF_04074};
DE AltName: Full=pX {ECO:0000255|HAMAP-Rule:MF_04074};
GN Name=X {ECO:0000255|HAMAP-Rule:MF_04074};
OS Hepatitis B virus genotype C subtype ayr (isolate Human/Japan/Okamoto/-)
OS (HBV-C).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC hepatitis B virus genotype C.
OX NCBI_TaxID=928302;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3783127; DOI=10.1099/0022-1317-67-11-2305;
RA Okamoto H., Imai M., Shimozaki M., Hoshi Y., Iizuka H., Gotanda T.,
RA Tsuda F., Miyakawa Y., Mayumi M.;
RT "Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr:
RT comparison with genomes of the other three subtypes.";
RL J. Gen. Virol. 67:2305-2314(1986).
RN [2]
RP HOMODIMERIZATION.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=2803288; DOI=10.1016/0006-291x(89)91676-8;
RA Lin M.H., Lo S.C.;
RT "Dimerization of hepatitis B viral X protein synthesized in a cell-free
RT system.";
RL Biochem. Biophys. Res. Commun. 164:14-21(1989).
RN [3]
RP FUNCTION.
RC STRAIN=Strain rutter 1979;
RX PubMed=2359621;
RA Faktor O., Shaul Y.;
RT "The identification of hepatitis B virus X gene responsive elements reveals
RT functional similarity of X and HTLV-I tax.";
RL Oncogene 5:867-872(1990).
RN [4]
RP PHOSPHORYLATION IN HEPG2 CELLS.
RC STRAIN=Strain rutter 1979;
RX PubMed=1923499;
RA Schek N., Bartenschlager R., Kuhn C., Schaller H.;
RT "Phosphorylation and rapid turnover of hepatitis B virus X-protein
RT expressed in HepG2 cells from a recombinant vaccinia virus.";
RL Oncogene 6:1735-1744(1991).
RN [5]
RP INTERACTION WITH HUMAN CREB1.
RC STRAIN=Strain rutter 1979;
RX PubMed=1827531; DOI=10.1126/science.1827531;
RA Maguire H.F., Hoeffler J.P., Siddiqui A.;
RT "HBV X protein alters the DNA binding specificity of CREB and ATF-2 by
RT protein-protein interactions.";
RL Science 252:842-844(1991).
RN [6]
RP SUBCELLULAR LOCATION.
RC STRAIN=Strain rutter 1979;
RX PubMed=7588604; DOI=10.1002/j.1460-2075.1995.tb00156.x;
RA Doria M., Klein N., Lucito R., Schneider R.J.;
RT "The hepatitis B virus HBx protein is a dual specificity cytoplasmic
RT activator of Ras and nuclear activator of transcription factors.";
RL EMBO J. 14:4747-4757(1995).
RN [7]
RP INTERACTION WITH HUMAN POLR2E.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=7828586; DOI=10.1002/j.1460-2075.1995.tb06984.x;
RA Cheong J.H., Yi M., Lin Y., Murakami S.;
RT "Human RPB5, a subunit shared by eukaryotic nuclear RNA polymerases, binds
RT human hepatitis B virus X protein and may play a role in X
RT transactivation.";
RL EMBO J. 14:143-150(1995).
RN [8]
RP FUNCTION.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=9054408; DOI=10.1074/jbc.272.11.7173;
RA Lin Y., Nomura T., Cheong J., Dorjsuren D., Iida K., Murakami S.;
RT "Hepatitis B virus X protein is a transcriptional modulator that
RT communicates with transcription factor IIB and the RNA polymerase II
RT subunit 5.";
RL J. Biol. Chem. 272:7132-7139(1997).
RN [9]
RP FUNCTION.
RC STRAIN=Strain rutter 1979;
RX PubMed=9488473; DOI=10.1128/mcb.18.3.1562;
RA Haviv I., Shamay M., Doitsh G., Shaul Y.;
RT "Hepatitis B virus pX targets TFIIB in transcription coactivation.";
RL Mol. Cell. Biol. 18:1562-1569(1998).
RN [10]
RP SUBCELLULAR LOCATION.
RC STRAIN=Strain rutter 1979;
RX PubMed=9572486; DOI=10.1038/sj.onc.1201737;
RA Sirma H., Weil R., Rosmorduc O., Urban S., Israel A., Kremsdorf D.,
RA Brechot C.;
RT "Cytosol is the prime compartment of hepatitis B virus X protein where it
RT colocalizes with the proteasome.";
RL Oncogene 16:2051-2063(1998).
RN [11]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RC STRAIN=Strain rutter 1979;
RX PubMed=10597295; DOI=10.1038/sj.onc.1203188;
RA Takada S., Shirakata Y., Kaneniwa N., Koike K.;
RT "Association of hepatitis B virus X protein with mitochondria causes
RT mitochondrial aggregation at the nuclear periphery, leading to cell
RT death.";
RL Oncogene 18:6965-6973(1999).
RN [12]
RP INTERACTION WITH HUMAN CEBPA.
RC STRAIN=Strain rutter 1979;
RX PubMed=9915821; DOI=10.1074/jbc.274.5.2858;
RA Choi B.H., Park G.T., Rho H.M.;
RT "Interaction of hepatitis B viral X protein and CCAAT/enhancer-binding
RT protein alpha synergistically activates the hepatitis B viral enhancer
RT II/pregenomic promoter.";
RL J. Biol. Chem. 274:2858-2865(1999).
RN [13]
RP INTERACTION WITH HUMAN NFKBIA.
RC STRAIN=Strain rutter 1979;
RX PubMed=10454581; DOI=10.1128/mcb.19.9.6345;
RA Weil R., Sirma H., Giannini C., Kremsdorf D., Bessia C., Dargemont C.,
RA Brechot C., Israel A.;
RT "Direct association and nuclear import of the hepatitis B virus X protein
RT with the NF-kappaB inhibitor IkappaBalpha.";
RL Mol. Cell. Biol. 19:6345-6354(1999).
RN [14]
RP SUBCELLULAR LOCATION.
RC STRAIN=Strain rutter 1979;
RX PubMed=11257193; DOI=10.1099/0022-1317-82-4-871;
RA Henkler F., Hoare J., Waseem N., Goldin R.D., McGarvey M.J., Koshy R.,
RA King I.A.;
RT "Intracellular localization of the hepatitis B virus HBx protein.";
RL J. Gen. Virol. 82:871-882(2001).
RN [15]
RP SUBCELLULAR LOCATION.
RC STRAIN=Strain rutter 1979;
RX PubMed=11468725; DOI=10.1002/jmv.1067;
RA Hoare J., Henkler F., Dowling J.J., Errington W., Goldin R.D., Fish D.,
RA McGarvey M.J.;
RT "Subcellular localisation of the X protein in HBV infected hepatocytes.";
RL J. Med. Virol. 64:419-426(2001).
RN [16]
RP PHOSPHORYLATION.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=11377708; DOI=10.1016/s0166-0934(00)00282-2;
RA Lee Y.I., Kim S.O., Kwon H.J., Park J.G., Sohn M.J., Jeong S.S.;
RT "Phosphorylation of purified recombinant hepatitis B virus-X protein by
RT mitogen-activated protein kinase and protein kinase C in vitro.";
RL J. Virol. Methods 95:1-10(2001).
RN [17]
RP INTERACTION WITH HUMAN SMAD4.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=11230153; DOI=10.1101/gad.856201;
RA Lee D.K., Park S.H., Yi Y., Choi S.G., Lee C., Parks W.T., Cho H.,
RA de Caestecker M.P., Shaul Y., Roberts A.B., Kim S.J.;
RT "The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family
RT signaling through direct interaction with Smad4: potential mechanism of
RT hepatitis B virus-induced liver fibrosis.";
RL Genes Dev. 15:455-466(2001).
RN [18]
RP INTERACTION WITH HUMAN CFLAR.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=12727877; DOI=10.1093/emboj/cdg210;
RA Kim K.H., Seong B.L.;
RT "Pro-apoptotic function of HBV X protein is mediated by interaction with c-
RT FLIP and enhancement of death-inducing signal.";
RL EMBO J. 22:2104-2116(2003).
RN [19]
RP INTERACTION WITH HUMAN HBXIP.
RC STRAIN=Isolate Japan/Nishioka/1983;
RX PubMed=12773388; DOI=10.1093/emboj/cdg263;
RA Marusawa H., Matsuzawa S., Welsh K., Zou H., Armstrong R., Tamm I.,
RA Reed J.C.;
RT "HBXIP functions as a cofactor of survivin in apoptosis suppression.";
RL EMBO J. 22:2729-2740(2003).
RN [20]
RP FUNCTION IN APOPTOSIS.
RC STRAIN=Strain rutter 1979;
RX PubMed=12676947; DOI=10.1074/jbc.m301606200;
RA Shirakata Y., Koike K.;
RT "Hepatitis B virus X protein induces cell death by causing loss of
RT mitochondrial membrane potential.";
RL J. Biol. Chem. 278:22071-22078(2003).
RN [21]
RP INTERACTION WITH HUMAN HSPD1/HSP60.
RC STRAIN=Strain rutter 1979;
RX PubMed=15120623; DOI=10.1016/j.bbrc.2004.04.046;
RA Tanaka Y., Kanai F., Kawakami T., Tateishi K., Ijichi H., Kawabe T.,
RA Arakawa Y., Kawakami T., Nishimura T., Shirakata Y., Koike K., Omata M.;
RT "Interaction of the hepatitis B virus X protein (HBx) with heat shock
RT protein 60 enhances HBx-mediated apoptosis.";
RL Biochem. Biophys. Res. Commun. 318:461-469(2004).
RN [22]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HOST TRPC4AP.
RX PubMed=26038816; DOI=10.1080/15384101.2015.1056946;
RA Jamal A., Swarnalatha M., Sultana S., Joshi P., Panda S.K., Kumar V.;
RT "The G1 phase E3 ubiquitin ligase TRUSS that gets deregulated in human
RT cancers is a novel substrate of the S-phase E3 ubiquitin ligase Skp2.";
RL Cell Cycle 14:2688-2700(2015).
RN [23]
RP FUNCTION, AND INTERACTION WITH HOST SMC5-SMC6 COMPLEX.
RX PubMed=26983541; DOI=10.1038/nature17170;
RA Decorsiere A., Mueller H., van Breugel P.C., Abdul F., Gerossier L.,
RA Beran R.K., Livingston C.M., Niu C., Fletcher S.P., Hantz O., Strubin M.;
RT "Hepatitis B virus X protein identifies the Smc5/6 complex as a host
RT restriction factor.";
RL Nature 531:386-389(2016).
RN [24]
RP REVIEW.
RX PubMed=15542625; DOI=10.1128/jvi.78.23.12725-12734.2004;
RA Bouchard M.J., Schneider R.J.;
RT "The enigmatic X gene of hepatitis B virus.";
RL J. Virol. 78:12725-12734(2004).
RN [25]
RP REVIEW.
RX PubMed=16984372; DOI=10.1111/j.1349-7006.2006.00299.x;
RA Tang H., Oishi N., Kaneko S., Murakami S.;
RT "Molecular functions and biological roles of hepatitis B virus x protein.";
RL Cancer Sci. 97:977-983(2006).
CC -!- FUNCTION: Multifunctional protein that plays a role in silencing host
CC antiviral defenses and promoting viral transcription. Does not seem to
CC be essential for HBV infection. May be directly involved in development
CC of cirrhosis and liver cancer (hepatocellular carcinoma). Most of
CC cytosolic activities involve modulation of cytosolic calcium. The
CC effect on apoptosis is controversial depending on the cell types in
CC which the studies have been conducted. May induce apoptosis by
CC localizing in mitochondria and causing loss of mitochondrial membrane
CC potential. May also modulate apoptosis by binding host CFLAR, a key
CC regulator of the death-inducing signaling complex (DISC)
CC (PubMed:10597295, PubMed:12676947). Promotes viral transcription by
CC using the host E3 ubiquitin ligase DDB1 to target the SMC5-SMC6 complex
CC to proteasomal degradation. This host complex would otherwise bind to
CC viral episomal DNA, and prevents its transcription (PubMed:26983541).
CC Moderately stimulates transcription of many different viral and
CC cellular transcription elements. Promoters and enhancers stimulated by
CC HBx contain DNA binding sites for NF-kappa-B, AP-1, AP-2, c-EBP,
CC ATF/CREB, or the calcium-activated factor NF-AT (PubMed:2359621,
CC PubMed:9054408, PubMed:9488473). {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:10597295, ECO:0000269|PubMed:12676947,
CC ECO:0000269|PubMed:2359621, ECO:0000269|PubMed:26983541,
CC ECO:0000269|PubMed:9054408, ECO:0000269|PubMed:9488473}.
CC -!- SUBUNIT: May form homodimer. May interact with host CEBPA, CFLAR,
CC CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4
CC (PubMed:1827531, PubMed:9915821, PubMed:10454581, PubMed:15120623,
CC PubMed:7828586, PubMed:12773388, PubMed:11230153, PubMed:12727877).
CC Interacts with host SMC5-SMC6 complex and induces its degradation
CC (PubMed:26983541). Interacts with host TRPC4AP; leading to prevent
CC ubiquitination of TRPC4AP (PubMed:26038816). {ECO:0000255|HAMAP-
CC Rule:MF_04074, ECO:0000269|PubMed:10454581,
CC ECO:0000269|PubMed:11230153, ECO:0000269|PubMed:12727877,
CC ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:15120623,
CC ECO:0000269|PubMed:1827531, ECO:0000269|PubMed:26038816,
CC ECO:0000269|PubMed:26983541, ECO:0000269|PubMed:2803288,
CC ECO:0000269|PubMed:7828586, ECO:0000269|PubMed:9915821}.
CC -!- INTERACTION:
CC Q69027; Q7Z434: MAVS; Xeno; NbExp=2; IntAct=EBI-3650820, EBI-995373;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:11257193, ECO:0000269|PubMed:11468725,
CC ECO:0000269|PubMed:26038816, ECO:0000269|PubMed:7588604,
CC ECO:0000269|PubMed:9572486}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04074, ECO:0000269|PubMed:11257193,
CC ECO:0000269|PubMed:11468725, ECO:0000269|PubMed:7588604}. Host
CC mitochondrion {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:10597295, ECO:0000269|PubMed:11257193}. Note=Mainly
CC cytoplasmic as only a fraction is detected in the nucleus. In
CC cytoplasm, a minor fraction associates with mitochondria or
CC proteasomes. {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:11257193}.
CC -!- PTM: A fraction may be phosphorylated in insect cells and HepG2 cells,
CC a human hepatoblastoma cell line. Phosphorylated in vitro by host
CC protein kinase C or mitogen-activated protein kinase. N-acetylated in
CC insect cells. {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:11377708, ECO:0000269|PubMed:1923499}.
CC -!- SIMILARITY: Belongs to the orthohepadnavirus protein X family.
CC {ECO:0000255|HAMAP-Rule:MF_04074}.
CC -!- CAUTION: Transcriptional activities should be taken with a grain of
CC salt. all studies demonstrating in vivo interaction between protein X
CC and transcriptional components were performed with significant
CC overexpression of both proteins and in the absence of viral infection.
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DR EMBL; X04615; CAA28288.1; -; Genomic_DNA.
DR DIP; DIP-60873N; -.
DR IntAct; Q69027; 6.
DR PRIDE; Q69027; -.
DR Proteomes; UP000008591; Genome.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039652; P:induction by virus of host NF-kappaB cascade; IEA:UniProtKB-UniRule.
DR GO; GO:0039592; P:suppression by virus of G2/M transition of host mitotic cell cycle; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0019079; P:viral genome replication; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04074; HBV_X; 1.
DR InterPro; IPR000236; Transactivation_prot_X.
DR Pfam; PF00739; X; 1.
PE 1: Evidence at protein level;
KW Activation of host NF-kappa-B by virus; Activator; Apoptosis;
KW Host cytoplasm; Host G2/M cell cycle arrest by virus; Host mitochondrion;
KW Host nucleus; Host-virus interaction;
KW Modulation of host cell cycle by virus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..154
FT /note="Protein X"
FT /id="PRO_0000390311"
FT REGION 68..117
FT /note="Mitochondrial targeting sequence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04074,
FT ECO:0000269|PubMed:12676947"
SQ SEQUENCE 154 AA; 16509 MW; 92E42028033315C4 CRC64;
MAARLCCQLD PARDVLCLRP VGAESRGRPV SGPFGPLPSP SSSAVPADHG AHLSLRGLPV
CAFSSAGPCA LRFTSARSME TTVNAHQVLP KVLHKRTLGL SAMSTTDLEA YFKDCLFKDW
EELGEEIRLK VFVLGGCRHK LVCSPAPCNF FPSA
