X_HBVC1
ID X_HBVC1 Reviewed; 154 AA.
AC P0C686;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 25-MAY-2022, entry version 48.
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 adr (isolate Japan/Nishioka/1983)
OS (HBV-C).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=482133;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6300776; DOI=10.1093/nar/11.6.1747;
RA Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K.;
RT "The complete nucleotide sequences of the cloned hepatitis B virus DNA;
RT subtype adr and adw.";
RL Nucleic Acids Res. 11:1747-1757(1983).
RN [2]
RP INTERACTION WITH HUMAN POLR2E.
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 [3]
RP FUNCTION.
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 [4]
RP INTERACTION WITH HUMAN HBXIP.
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 [5]
RP PHOSPHORYLATION.
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 [6]
RP INTERACTION WITH HUMAN SMAD4.
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 [7]
RP INTERACTION WITH HUMAN CFLAR.
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 [8]
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 [9]
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:9054408}.
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 -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04074}.
CC Host nucleus {ECO:0000255|HAMAP-Rule:MF_04074}. Host mitochondrion
CC {ECO:0000255|HAMAP-Rule:MF_04074}. Note=Mainly cytoplasmic as only a
CC fraction is detected in the nucleus. In cytoplasm, a minor fraction
CC associates with mitochondria or proteasomes. {ECO:0000255|HAMAP-
CC Rule:MF_04074}.
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}.
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; D00630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR SMR; P0C686; -.
DR Proteomes; UP000007921; 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_0000319905"
FT REGION 68..117
FT /note="Mitochondrial targeting sequence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04074"
SQ SEQUENCE 154 AA; 16590 MW; C0A9C33C82143FA4 CRC64;
MAARVCCQLD PARDVLCLRP VGAESRGRPV SGPFGPLPSP SSSAVPADHG ARLSLRGLPV
CAFSSAGPCA LRFTSARRME TTVNAHQVLP KVLHKRTLGL SAMSTTDLEA YFKDCLFKDW
EELGEEIRLM VFVLGGCRHK LVCSPAPCNF FTSA
