X_HBVA3
ID X_HBVA3 Reviewed; 154 AA.
AC P69713; P03166; P12935;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 64.
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 A2 subtype adw2 (strain Rutter 1979) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=480116;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J.;
RT "The nucleotide sequence of the hepatitis B viral genome and the
RT identification of the major viral genes.";
RL (In) Field B.N., Jaenisch R., Fox C.F. (eds.);
RL Animal virus genetics, pp.57-70, Academic Press, New York (1980).
RN [2]
RP PROMOTER STIMULATION.
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 [3]
RP PHOSPHORYLATION IN HEPG2 CELLS.
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 [4]
RP INTERACTION WITH HUMAN CREB1.
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 [5]
RP SUBCELLULAR LOCATION.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=9328333; DOI=10.1002/hep.510260437;
RA Urban S., Hildt E., Eckerskorn C., Sirma H., Kekule A., Hofschneider P.H.;
RT "Isolation and molecular characterization of hepatitis B virus X-protein
RT from a baculovirus expression system.";
RL Hepatology 26:1045-1053(1997).
RN [7]
RP INTERACTION WITH HUMAN CELL TRANSCRIPTION MACHINERY.
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 [8]
RP SUBCELLULAR LOCATION.
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 [9]
RP FUNCTION.
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 [10]
RP INTERACTION WITH HUMAN CEBPA.
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 [11]
RP INTERACTION WITH HUMAN NFKBIA.
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 [12]
RP SUBCELLULAR LOCATION.
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 [13]
RP SUBCELLULAR LOCATION.
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 [14]
RP FUNCTION IN APOPTOSIS.
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 [15]
RP INTERACTION WITH HUMAN HSPD1/HSP60.
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 [16]
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 [17]
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). Promotes
CC viral transcription by using the host E3 ubiquitin ligase DDB1 to
CC target the SMC5-SMC6 complex to proteasomal degradation. This host
CC complex would otherwise bind to viral episomal DNA, and prevents its
CC transcription. Moderately stimulates transcription of many different
CC viral and cellular transcription elements. Promoters and enhancers
CC stimulated by HBx contain DNA binding sites for NF-kappa-B, AP-1, AP-2,
CC c-EBP, ATF/CREB, or the calcium-activated factor NF-AT.
CC {ECO:0000255|HAMAP-Rule:MF_04074, ECO:0000269|PubMed:10597295,
CC ECO:0000269|PubMed:12676947}.
CC -!- SUBUNIT: May form homodimer. May interact with host CEBPA, CFLAR,
CC CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4.
CC Interacts with host SMC5-SMC6 complex and induces its degradation.
CC {ECO:0000255|HAMAP-Rule:MF_04074}.
CC -!- INTERACTION:
CC P69713; Q8IUQ4: SIAH1; Xeno; NbExp=4; IntAct=EBI-7088789, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04074,
CC ECO:0000269|PubMed:11468725, ECO:0000269|PubMed:7588604,
CC ECO:0000269|PubMed:9572486}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04074, ECO:0000269|PubMed:11468725, ECO:0000269|PubMed:7588604,
CC ECO:0000269|PubMed:9572486}. Host mitochondrion {ECO:0000255|HAMAP-
CC Rule:MF_04074, ECO:0000269|PubMed:11257193}. Note=Mainly cytoplasmic as
CC only a fraction is detected in the nucleus. In cytoplasm, a minor
CC fraction associates with mitochondria or proteasomes.
CC {ECO:0000255|HAMAP-Rule:MF_04074, ECO:0000269|PubMed:11257193,
CC ECO:0000269|PubMed:9572486}.
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: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. As of 2007, all studies demonstrating in vivo interaction between
CC protein X and transcriptional components were performed with
CC significant overexpression of both proteins and in the absence of viral
CC infection.
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DR EMBL; X02763; CAA26540.1; -; Genomic_DNA.
DR PIR; A31289; QQVLAW.
DR PIR; S47408; S47408.
DR SMR; P69713; -.
DR IntAct; P69713; 4.
DR MINT; P69713; -.
DR Proteomes; UP000008766; 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; Transcription;
KW Transcription regulation.
FT CHAIN 1..154
FT /note="Protein X"
FT /id="PRO_0000222359"
FT REGION 68..117
FT /note="Mitochondrial targeting sequence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04074"
FT VARIANT 12
FT /note="S -> A (in expression vector pCMVX)"
FT VARIANT 109
FT /note="E -> A (in expression vector pCMVX)"
SQ SEQUENCE 154 AA; 16583 MW; 7F2AE32A4F025670 CRC64;
MAARLYCQLD PSRDVLCLRP VGAESRGRPL SGPLGTLSSP SPSAVPADHG AHLSLRGLPV
CAFSSAGPCA LRFTSARCME TTVNAHQILP KVLHKRTLGL PAMSTTDLEA YFKDCVFKDW
EELGEEIRLK VFVLGGCRHK LVCAPAPCNF FTSA
