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Gene Review

LAMTOR5  -  late endosomal/lysosomal adaptor, MAPK and...

Homo sapiens

Synonyms: HBV X-interacting protein, HBX-interacting protein, HBXIP, Hepatitis B virus X-interacting protein, Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5, ...
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Disease relevance of HBXIP


High impact information on HBXIP

  • We further show that acyl CoAs may interact directly with the XIP (exchanger inhibitory peptide) sequence, a known region of anionic lipid modulation, to dynamically regulate NCX1 activity and Ca(2+) homeostasis [3].
  • HBXIP functions as a cofactor of survivin in apoptosis suppression [1].
  • As defined by the HUMARA assay, 53 of 78 patients had persistent polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis and in 4 of 10 with clonal hematopoiesis [4].
  • At the time of ABMT, the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X-inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3% (3/104) [4].
  • Thus, viral HBx and its cellular target HBXIP regulate centrosome dynamics and cytokinesis affecting genetic stability [5].

Chemical compound and disease context of HBXIP


Biological context of HBXIP

  • We propose that one of the physiologic functions of the cellular protein XIP is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus [2].
  • Thus, HBXIP is a critical regulator of hepatocyte cell growth in vivo, making it a strong candidate for explaining the tumorigenic actions of viral HBx [5].
  • The hepatitis B virus genome encodes an oncoprotein, HBx, which binds various cellular proteins including HBXIP [5].
  • We found that most cells deficient in HBXIP arrest in prometaphase with monopolar spindles whereas HBXIP overexpression causes tripolar or multipolar spindles due to excessive centrosome replication [5].
  • In vivo experiments using antisense oligonucleotides targeting HBXIP in a mouse model of liver regeneration showed a requirement for HBXIP for growth and survival of replicating hepatocytes [5].

Anatomical context of HBXIP

  • Additionally, a defect in cytokinesis was seen in HBXIP-deficient HeLa cells, with most cells failing to complete division and succumbing eventually to apoptosis [5].
  • Immunolocalization and fluorescent protein tagging experiments showed that HBXIP associates with microtubules of dividing cells and colocalizes with HBx on centrosomes [5].
  • We show here that HBXIP is a regulator of centrosome duplication, required for bipolar spindle formation in HeLa human carcinoma cells and primary mouse embryonic fibroblast cells [5].
  • The inhibitory effects of Na+/Ca2+ exchange inhibitory peptide (XIP), which corresponds to residues 219-238 of the Na+/Ca2+ exchange protein from canine heart, were studied in both rat and human brain plasma membrane vesicles [6].
  • By whole-cell voltage clamping experiments, we demonstrate that deletion of residues 562-679, but not 440- 456, 498-510, or 680-685 of the f-loop selectively eliminates XIP-mediated inhibition of NCX expressed either heterologously (HEK293 and A549 cells) or in guinea pig cardiac myocytes [7].

Associations of HBXIP with chemical compounds

  • Furthermore, the role of the relatively recently discovered cereal endoxylanase inhibitor families TAXI (Triticum aestivum xylanase inhibitor) and XIP (xylanase inhibitor protein) in plant defense is discussed [8].
  • Also, contractions that are activated in the presence of nifedipine are sensitive to the Na-Ca exchange inhibitor XIP [9].
  • Use of cysteine replacements and chemical modification to alter XIP, the autoinhibitory region of the Na-Ca exchanger. Inhibition of the activated plasma membrane Ca pump [10].
  • Sulfosuccinimidyl acetate (SNA)-modified XIP does not inhibit the Ca pump; SNA neutralizes the positive charge on Lys at positions 7, 11, and 17 [11].
  • Three peptide analogues, in which 7, 11, and 17 were Ala, Cys, or Lys, inhibited about as well as XIP [11].

Other interactions of HBXIP

  • CONCLUSION: Elevated levels of GDN/PN1 and XIP mRNAs induced by Allitridi provide valuable molecular evidence for elucidating the garlic's efficacies against neurodegenerative and inflammatory diseases [12].
  • In the cytoplasm, survivin inhibits apoptosis by interacting with caspase-9 in the presence of the HBXIP cofactor, by binding to Smac or associating with XIAP [13].
  • From yeast two hybrid screening with HBX as bait, human guanine nucleotide binding protein beta subunit 5L (GNbeta5) was isolated from the cDNA library constructed in this study as a new HBX-interacting protein [14].

Analytical, diagnostic and therapeutic context of HBXIP


  1. HBXIP functions as a cofactor of survivin in apoptosis suppression. Marusawa, H., Matsuzawa, S., Welsh, K., Zou, H., Armstrong, R., Tamm, I., Reed, J.C. EMBO J. (2003) [Pubmed]
  2. Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication. Melegari, M., Scaglioni, P.P., Wands, J.R. J. Virol. (1998) [Pubmed]
  3. Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. Riedel, M.J., Baczk??, I., Searle, G.J., Webster, N., Fercho, M., Jones, L., Lang, J., Lytton, J., Dyck, J.R., Light, P.E. EMBO J. (2006) [Pubmed]
  4. Predictive value of clonality assays in patients with non-Hodgkin's lymphoma undergoing autologous bone marrow transplant: a single institution study. Mach-Pascual, S., Legare, R.D., Lu, D., Kroon, M., Neuberg, D., Tantravahi, R., Stone, R.M., Freedman, A.S., Nadler, L.M., Gribben, J.G., Gilliland, D.G. Blood (1998) [Pubmed]
  5. HBXIP, Cellular Target of Hepatitis B Virus Oncoprotein, Is a Regulator of Centrosome Dynamics and Cytokinesis. Fujii, R., Zhu, C., Wen, Y., Marusawa, H., Bailly-Maitre, B., Matsuzawa, S., Zhang, H., Kim, Y., Bennett, C.F., Jiang, W., Reed, J.C. Cancer Res. (2006) [Pubmed]
  6. Characterization of exchange inhibitory peptide effects on Na+/Ca2+ exchange in rat and human brain plasma membrane vesicles. Wu, A., Colvin, R.A. J. Neurochem. (1994) [Pubmed]
  7. Cardiac sodium-calcium exchanger is regulated by allosteric calcium and exchanger inhibitory peptide at distinct sites. Maack, C., Ganesan, A., Sidor, A., O'Rourke, B. Circ. Res. (2005) [Pubmed]
  8. Microbial endoxylanases: effective weapons to breach the plant cell-wall barrier or, rather, triggers of plant defense systems? Beli??n, T., Van Campenhout, S., Robben, J., Volckaert, G. Mol. Plant Microbe Interact. (2006) [Pubmed]
  9. Evidence that reverse Na-Ca exchange can trigger SR calcium release. Litwin, S., Kohmoto, O., Levi, A.J., Spitzer, K.W., Bridge, J.H. Ann. N. Y. Acad. Sci. (1996) [Pubmed]
  10. Use of cysteine replacements and chemical modification to alter XIP, the autoinhibitory region of the Na-Ca exchanger. Inhibition of the activated plasma membrane Ca pump. Xu, W.Y., Gatto, C., Allen, C.J., Milanick, M.A. Ann. N. Y. Acad. Sci. (1996) [Pubmed]
  11. Positive charge modifications alter the ability of XIP to inhibit the plasma membrane calcium pump. Xu, W., Gatto, C., Milanick, M.A. Am. J. Physiol. (1996) [Pubmed]
  12. Applying a highly specific and reproducible cDNA RDA method to clone garlic up-regulated genes in human gastric cancer cells. Li, Y., Lu, Y.Y. World J. Gastroenterol. (2002) [Pubmed]
  13. An IAP in action: the multiple roles of survivin in differentiation, immunity and malignancy. Zangemeister-Wittke, U., Simon, H.U. Cell Cycle (2004) [Pubmed]
  14. Hepatitis B virus X protein interacts with beta5 subunit of heterotrimeric guanine nucleotide binding protein. Lwa, S.H., Chen, W.N. Virol. J. (2005) [Pubmed]
  15. Purification and characterization of a XIP-type endoxylanase inhibitor from rice (Oryza sativa). Goesaert, H., Gebruers, K., Courtin, C.M., Delcour, J.A. Journal of enzyme inhibition and medicinal chemistry. (2005) [Pubmed]
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