ID   X_HBVB4                 Reviewed;         154 AA.
AC   P20977;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   10-JUN-2026, entry version 84.
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 B/C subtype adw (isolate Okinawa/pODW282/1998)
OS   (HBV-B).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC   Orthohepadnavirus hominoidei; Hepatitis B virus.
OX   NCBI_TaxID=10415;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3171552; DOI=10.1099/0022-1317-69-10-2575;
RA   Okamoto H., Tsuda F., Sakugawa H., Sastrosoewignjo R.I., Imai M.,
RA   Miyakawa Y., Mayumi M.;
RT   "Typing hepatitis B virus by homology in nucleotide sequence: comparison of
RT   surface antigen subtypes.";
RL   J. Gen. Virol. 69:2575-2583(1988).
RN   [2]
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   [3]
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}.
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       Interacts with host TRPC4AP; leading to prevent ubiquitination of
CC       TRPC4AP. Interacts with host PLSCR1; this interaction promotes
CC       ubiquitination and degradation of HBx and impairs HBx-mediated cell
CC       proliferation. {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   -!- 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; D00330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; JS0603; JS0603.
DR   SMR; P20977; -.
DR   Proteomes; UP000007916; Segment.
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:0006351; P:DNA-templated transcription; IEA:UniProtKB-UniRule.
DR   GO; GO:0085033; P:symbiont-mediated activation of host NF-kappaB cascade; IEA:UniProtKB-UniRule.
DR   GO; GO:0039592; P:symbiont-mediated arrest of host cell cycle during G2/M transition; 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   3: Inferred from homology;
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_0000222368"
FT   REGION          68..117
FT                   /note="Mitochondrial targeting sequence"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04074"
SQ   SEQUENCE   154 AA;  16558 MW;  E2646C059A30125F CRC64;
     MAARLCCQLD PARDVLCLRP VGAESRGRPF PGPLGALPPA SPPVVPTDHG AHLSLRGLPV
     CAFSSAGPCA LRFTSARRME TTVNAHGNLP KVLHKRTLGL SAMSTTDLEA YFKDCVFNEW
     EELGEEVRLK VFVLGGCRHK LVCSPAPCNF FTSA
//