BAG3
BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the BAG3 gene.[1][2][3]
BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner.[3] BAG gene has been implicated in age related neurodegenerative diseases as Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.[4] It has also been shown to be the cause of familial dilated cardiomyopathy.[5]
Interactions
BAG3 has been shown to interact with HSPA8,[1] HSPA1A[6][7] and PLCG1.[6]
References
- ^ a b Takayama S, Xie Z, Reed JC (Feb 1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". J Biol Chem 274 (2): 781–6. doi:10.1074/jbc.274.2.781. PMID 9873016.
- ^ Carra S, Seguin SJ, Landry J (Jan 2008). "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy". Autophagy 4 (2): 237–9. PMID 18094623.
- ^ a b "Entrez Gene: BAG3 BCL2-associated athanogene 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9531.
- ^ Physorg:Old Cells Work Differently
- ^ Norton, N; Li, D, Rieder, MJ, Siegfried, JD, Rampersaud, E, Züchner, S, Mangos, S, Gonzalez-Quintana, J, Wang, L, McGee, S, Reiser, J, Martin, E, Nickerson, DA, Hershberger, RE (2011 Mar 11). "Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.". American journal of human genetics 88 (3): 273–82. doi:10.1016/j.ajhg.2011.01.016. PMC 3059419. PMID 21353195. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3059419.
- ^ a b Doong, H; Price J, Kim Y S, Gasbarre C, Probst J, Liotta L A, Blanchette J, Rizzo K, Kohn E (Sep. 2000). "CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70". Oncogene (ENGLAND) 19 (38): 4385–95. doi:10.1038/sj.onc.1203797. ISSN 0950-9232. PMID 10980614.
- ^ Antoku, K; Maser R S, Scully W J, Delach S M, Johnson D E (Sep. 2001). "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein". Biochem. Biophys. Res. Commun. (United States) 286 (5): 1003–10. doi:10.1006/bbrc.2001.5512. ISSN 0006-291X. PMID 11527400.
External links
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Lee JH, Takahashi T, Yasuhara N, et al. (2000). "Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death.". Oncogene 18 (46): 6183–90. doi:10.1038/sj.onc.1203043. PMID 10597216.
- Doong H, Price J, Kim YS, et al. (2000). "CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70.". Oncogene 19 (38): 4385–95. doi:10.1038/sj.onc.1203797. PMID 10980614.
- Liao Q, Ozawa F, Friess H, et al. (2001). "The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.". FEBS Lett. 503 (2-3): 151–7. doi:10.1016/S0014-5793(01)02728-4. PMID 11513873.
- Antoku K, Maser RS, Scully WJ, et al. (2001). "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein.". Biochem. Biophys. Res. Commun. 286 (5): 1003–10. doi:10.1006/bbrc.2001.5512. PMID 11527400.
- Suzuki H, Fukunishi Y, Kagawa I, et al. (2001). "Protein-protein interaction panel using mouse full-length cDNAs.". Genome Res. 11 (10): 1758–65. doi:10.1101/gr.180101. PMC 311163. PMID 11591653. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311163.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Romano MF, Festa M, Pagliuca G, et al. (2003). "BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis.". Cell Death Differ. 10 (3): 383–5. doi:10.1038/sj.cdd.4401167. PMID 12700638.
- Pagliuca MG, Lerose R, Cigliano S, Leone A (2003). "Regulation by heavy metals and temperature of the human BAG-3 gene, a modulator of Hsp70 activity.". FEBS Lett. 541 (1-3): 11–5. doi:10.1016/S0014-5793(03)00274-6. PMID 12706811.
- Doong H, Rizzo K, Fang S, et al. (2003). "CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins.". J. Biol. Chem. 278 (31): 28490–500. doi:10.1074/jbc.M209682200. PMID 12750378.
- Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins.". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Rush J, Moritz A, Lee KA, et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
- Tao WA, Wollscheid B, O'Brien R, et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry.". Nat. Methods 2 (8): 591–8. doi:10.1038/nmeth776. PMID 16094384.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- Seo YJ, Jeon MH, Lee JH, et al. (2006). "Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27.". Exp. Mol. Med. 37 (6): 624–30. PMID 16391524.
- Kassis JN, Guancial EA, Doong H, et al. (2006). "CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins.". Exp. Cell Res. 312 (15): 2962–71. doi:10.1016/j.yexcr.2006.05.023. PMID 16859681.
- Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization.". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
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1uk5: Solution structure of the Murine BAG domain of Bcl2-associated athanogene 3
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