BAG1

BCL2-associated athanogene
PDB rendering based on 1hx1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HX1​, 1WXV​, 3FZF​, 3FZH​, 3FZK​, 3FZL​, 3FZM​, 3LDQ​, 3M3Z​
Identifiers
Symbols	BAG1 ; BAG-1; HAP; RAP46
External IDs	OMIM: 601497 MGI: 108047 HomoloGene: 3190 GeneCards: BAG1 Gene
Gene ontology Molecular function • receptor signaling protein activity • protein binding • chaperone binding Cellular component • nucleus • cytoplasm • cytosol Biological process • apoptotic process • cell surface receptor signaling pathway • cellular response to heat • intracellular signal transduction • negative regulation of apoptotic process • chaperone cofactor-dependent protein refolding • regulation of cellular response to heat Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	573	12017
Ensembl	ENSG00000107262	ENSMUSG00000028416
UniProt	Q99933	Q60739
RefSeq (mRNA)	NM_001172415	NM_001171739
RefSeq (protein)	NP_001165886	NP_001165210
Location (UCSC)	Chr 9: 33.25 – 33.26 Mb	Chr 4: 40.94 – 40.95 Mb
PubMed search

BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.^[1]

Function

The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. At least three protein isoforms are encoded by this mRNA through the use of alternative translation initiation sites, including a non-AUG site.^[2]

Clinical significance

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.^[3]

Interactions

BAG1 has been shown to interact with:

• Androgen receptor,^[4][5][6]
• C-Raf,^[7]
• Calcitriol receptor,^[8]
• Glucocorticoid receptor,^[9][10]
• HSPA8,^[11][12]
• HBEGF,^[13]
• PPP1R15A,^[14]
• NR1B1,^[15] and
• SIAH1.^[16]

References

1. Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC (March 1995). "Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity". Cell 80 (2): 279–84. doi:10.1016/0092-8674(95)90410-7. PMID 7834747.
2. "Entrez Gene: BAG1 BCL2-associated athanogene".
3. Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C (2009). "Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3". EMBO J. 28 (7): 889–901. doi:10.1038/emboj.2009.29. PMC 2647772. PMID 19229298. Lay summary – Physorg.
4. Shatkina L, Mink S, Rogatsch H, Klocker H, Langer G, Nestl A, Cato AC (October 2003). "The cochaperone Bag-1L enhances androgen receptor action via interaction with the NH2-terminal region of the receptor". Mol. Cell. Biol. 23 (20): 7189–97. doi:10.1128/mcb.23.20.7189-7197.2003. PMC 230325. PMID 14517289.
5. Knee DA, Froesch BA, Nuber U, Takayama S, Reed JC (April 2001). "Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activity". J. Biol. Chem. 276 (16): 12718–24. doi:10.1074/jbc.M010841200. PMID 11278763.
6. Froesch BA, Takayama S, Reed JC (May 1998). "BAG-1L protein enhances androgen receptor function". J. Biol. Chem. 273 (19): 11660–6. doi:10.1074/jbc.273.19.11660. PMID 9565586.
7. Wang HG, Takayama S, Rapp UR, Reed JC (July 1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1". Proc. Natl. Acad. Sci. U.S.A. 93 (14): 7063–8. doi:10.1073/pnas.93.14.7063. PMC 38936. PMID 8692945.
8. Guzey M, Takayama S, Reed JC (Dec 2000). "BAG1L enhances trans-activation function of the vitamin D receptor". J. Biol. Chem. 275 (52): 40749–56. doi:10.1074/jbc.M004977200. PMID 10967105.
9. Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, Cato AC (June 1998). "RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis". J. Biol. Chem. 273 (23): 14620–5. doi:10.1074/jbc.273.23.14620. PMID 9603979.
10. Schneikert J, Hübner S, Langer G, Petri T, Jäättelä M, Reed J, Cato AC (Dec 2000). "Hsp70-RAP46 interaction in downregulation of DNA binding by glucocorticoid receptor". EMBO J. 19 (23): 6508–16. doi:10.1093/emboj/19.23.6508. PMC 305849. PMID 11101523.
11. Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimoto RI, Reed JC (August 1997). "BAG-1 modulates the chaperone activity of Hsp70/Hsc70". EMBO J. 16 (16): 4887–96. doi:10.1093/emboj/16.16.4887. PMC 1170124. PMID 9305631.
12. Takayama S, Xie Z, Reed JC (January 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.
13. Lin J, Hutchinson L, Gaston SM, Raab G, Freeman MR (August 2001). "BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: a unique role for proHB-EGF in cell survival regulation". J. Biol. Chem. 276 (32): 30127–32. doi:10.1074/jbc.M010237200. PMID 11340068.
14. Hung WJ, Roberson RS, Taft J, Wu DY (May 2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. 23 (10): 3477–86. doi:10.1128/mcb.23.10.3477-3486.2003. PMC 164759. PMID 12724406.
15. Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X, Reed JC, Zhang XK (July 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". J. Biol. Chem. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID 9642262.
16. Matsuzawa S, Takayama S, Froesch BA, Zapata JM, Reed JC (May 1998). "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1". EMBO J. 17 (10): 2736–47. doi:10.1093/emboj/17.10.2736. PMC 1170614. PMID 9582267.

Further reading

• Tang SC (2003). "BAG-1, an anti-apoptotic tumour marker.". IUBMB Life 53 (2): 99–105. doi:10.1080/15216540211473. PMID 12049201.
• Clemo NK, Arhel NJ, Barnes JD; et al. (2005). "The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival.". Biochem. Soc. Trans. 33 (Pt 4): 676–8. doi:10.1042/BST0330676. PMID 16042572.
• Gehring U (2007). "Activities of the cochaperones Hap46/BAG-1M and Hap50/BAG-1L and isoforms.". Cell Stress Chaperones 11 (4): 295–303. doi:10.1379/1466-1268(2006)11[295:AOTCBA]2.0.CO;2. PMC 1712677. PMID 17278878.
• 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.
• Zeiner M, Gehring U (1996). "A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning.". Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11465–9. doi:10.1073/pnas.92.25.11465. PMC 40422. PMID 8524784.
• Wang HG, Takayama S, Rapp UR, Reed JC (1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.". Proc. Natl. Acad. Sci. U.S.A. 93 (14): 7063–8. doi:10.1073/pnas.93.14.7063. PMC 38936. PMID 8692945.
• Takayama S, Kochel K, Irie S; et al. (1996). "Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12.". Genomics 35 (3): 494–8. doi:10.1006/geno.1996.0389. PMID 8812483.
• Bardelli A, Longati P, Albero D; et al. (1997). "HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death.". EMBO J. 15 (22): 6205–12. PMC 452442. PMID 8947043.
• Takayama S, Bimston DN, Matsuzawa S; et al. (1997). "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.". EMBO J. 16 (16): 4887–96. doi:10.1093/emboj/16.16.4887. PMC 1170124. PMID 9305631.
• 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.
• Packham G, Brimmell M, Cleveland JL (1998). "Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation.". Biochem. J. 328. ( Pt 3): 807–13. PMC 1218990. PMID 9396724.
• Matsuzawa S, Takayama S, Froesch BA; et al. (1998). "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1.". EMBO J. 17 (10): 2736–47. doi:10.1093/emboj/17.10.2736. PMC 1170614. PMID 9582267.
• Kullmann M, Schneikert J, Moll J; et al. (1998). "RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis.". J. Biol. Chem. 273 (23): 14620–5. doi:10.1074/jbc.273.23.14620. PMID 9603979.
• Liu R, Takayama S, Zheng Y; et al. (1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells.". J. Biol. Chem. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID 9642262.
• Takayama S, Krajewski S, Krajewska M; et al. (1998). "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines.". Cancer Res. 58 (14): 3116–31. PMID 9679980.
• Takayama S, Xie Z, Reed JC (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.
• Yang X, Pater A, Tang SC (1999). "Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumor-derived p53 mutants.". Oncogene 18 (32): 4546–53. doi:10.1038/sj.onc.1202843. PMID 10467399.
• Schneikert J, Hübner S, Martin E, Cato AC (1999). "A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of glucocorticoid receptor activity.". J. Cell Biol. 146 (5): 929–40. doi:10.1083/jcb.146.5.929. PMC 2169481. PMID 10477749.
• Lüders J, Demand J, Höhfeld J (2000). "The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome.". J. Biol. Chem. 275 (7): 4613–7. doi:10.1074/jbc.275.7.4613. PMID 10671488.