X_HBVD3
ID X_HBVD3 Reviewed; 154 AA.
AC P03165;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 25-MAY-2022, entry version 99.
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 D subtype ayw (isolate France/Tiollais/1979)
OS (HBV-D).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC hepatitis B virus genotype D.
OX NCBI_TaxID=490133;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=399327; DOI=10.1038/281646a0;
RA Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P.;
RT "Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned
RT in E. coli.";
RL Nature 281:646-650(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Latvia;
RX PubMed=3996597; DOI=10.1016/0014-5793(85)80771-7;
RA Bichko V., Pushko P., Dreilina D., Pumpen P., Gren E.Y.;
RT "Subtype ayw variant of hepatitis B virus. DNA primary structure
RT analysis.";
RL FEBS Lett. 185:208-212(1985).
RN [3]
RP CHARACTERIZATION.
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 [4]
RP INTERACTION WITH HUMAN DDB1, AND MUTAGENESIS OF 77-ARG-ARG-78; LYS-91;
RP 95-LYS-ARG-96; LEU-98; ASP-107 AND 113-LYS-ASP-114.
RC STRAIN=Switzerland/Strubin/1999;
RX PubMed=11531405; DOI=10.1006/viro.2001.1036;
RA Lin-Marq N., Bontron S., Leupin O., Strubin M.;
RT "Hepatitis B virus X protein interferes with cell viability through
RT interaction with the p127-kDa UV-damaged DNA-binding protein.";
RL Virology 287:266-274(2001).
RN [5]
RP INTERACTION WITH HUMAN DDB1.
RC STRAIN=Switzerland/Strubin/1999;
RX PubMed=12151405; DOI=10.1074/jbc.m205722200;
RA Bontron S., Lin-Marq N., Strubin M.;
RT "Hepatitis B virus X protein associated with UV-DDB1 induces cell death in
RT the nucleus and is functionally antagonized by UV-DDB2.";
RL J. Biol. Chem. 277:38847-38854(2002).
RN [6]
RP INTERACTION WITH HUMAN DDB1.
RC STRAIN=Switzerland/Strubin/1999;
RX PubMed=12743284; DOI=10.1128/jvi.77.11.6274-6283.2003;
RA Leupin O., Bontron S., Strubin M.;
RT "Hepatitis B virus X protein and simian virus 5 V protein exhibit similar
RT UV-DDB1 binding properties to mediate distinct activities.";
RL J. Virol. 77:6274-6283(2003).
RN [7]
RP FUNCTION.
RC STRAIN=Switzerland/Strubin/1999;
RX PubMed=15767425; DOI=10.1128/jvi.79.7.4238-4245.2005;
RA Leupin O., Bontron S., Schaeffer C., Strubin M.;
RT "Hepatitis B virus X protein stimulates viral genome replication via a
RT DDB1-dependent pathway distinct from that leading to cell death.";
RL J. Virol. 79:4238-4245(2005).
RN [8]
RP INTERACTION WITH E4F1.
RX PubMed=16112766; DOI=10.1016/j.virusres.2005.07.003;
RA Rui E., Moura P.R., Goncalves K.A., Rooney R.J., Kobarg J.;
RT "Interaction of the hepatitis B virus protein HBx with the human
RT transcription regulatory protein p120E4F in vitro.";
RL Virus Res. 115:31-42(2006).
RN [9]
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 [10]
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:15767425}.
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 P03165; P31749: AKT1; Xeno; NbExp=3; IntAct=EBI-7683985, EBI-296087;
CC P03165; P31750: Akt1; Xeno; NbExp=2; IntAct=EBI-7683985, EBI-298707;
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; V01460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X02496; CAB41697.1; -; Genomic_DNA.
DR PIR; A03719; QQVLD1.
DR PIR; A05237; QQVLBH.
DR SMR; P03165; -.
DR IntAct; P03165; 4.
DR MINT; P03165; -.
DR Proteomes; UP000007930; 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_0000222361"
FT REGION 68..117
FT /note="Mitochondrial targeting sequence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04074"
FT VARIANT 26
FT /note="R -> C (in strain: Switzerland/Strubin/1999)"
FT VARIANT 33
FT /note="S -> P (in strain: Switzerland/Strubin/1999)"
FT VARIANT 36
FT /note="T -> A (in strain: Switzerland/Strubin/1999)"
FT VARIANT 40..43
FT /note="PSPS -> SSLP (in strain: Switzerland/Strubin/1999)"
FT VARIANT 46
FT /note="P -> S (in strain: Latvia)"
FT VARIANT 47..48
FT /note="TD -> AA (in strain: Switzerland/Strubin/1999)"
FT VARIANT 84..88
FT /note="NAHQI -> KAQPF (in strain: Latvia)"
FT VARIANT 102
FT /note="A -> V (in strain: Latvia)"
FT MUTAGEN 77..78
FT /note="RR->EE: No effect on interaction with human DDB1."
FT /evidence="ECO:0000269|PubMed:11531405"
FT MUTAGEN 91
FT /note="K->E: No effect on interaction with human DDB1."
FT /evidence="ECO:0000269|PubMed:11531405"
FT MUTAGEN 95
FT /note="K->E: No effect on interaction with human DDB1."
FT MUTAGEN 96
FT /note="R->E: Complete loss of interaction with human DDB1."
FT MUTAGEN 98
FT /note="L->F: Complete loss of interaction with human DDB1."
FT /evidence="ECO:0000269|PubMed:11531405"
FT MUTAGEN 107
FT /note="D->R: No effect on interaction with human DDB1."
FT /evidence="ECO:0000269|PubMed:11531405"
FT MUTAGEN 113..114
FT /note="KD->ER: No effect on interaction with human DDB1."
FT /evidence="ECO:0000269|PubMed:11531405"
SQ SEQUENCE 154 AA; 16618 MW; 29FD1CC9E09A34B5 CRC64;
MAARLCCQLD PARDVLCLRP VGAESRGRPF SGSLGTLSSP SPSAVPTDHG AHLSLRGLPV
CAFSSAGPCA LRFTSARRME TTVNAHQILP KVLHKRTLGL SAMSTTDLEA YFKDCLFKDW
EELGEEIRLK VFVLGGCRHK LVCAPAPCNF FTSA
