BAG1

BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.[5]

BAG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1HX1, 1WXV, 3FZF, 3FZH, 3FZK, 3FZL, 3FZM, 3LDQ, 3M3Z
Identifiers
Aliases	BAG1, BAG-1, HAP, RAP46, BCL2 associated athanogene 1, BAG cochaperone 1
External IDs	OMIM: 601497 MGI: 108047 HomoloGene: 3190 GeneCards: BAG1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9p13.3 Start 33,247,820 bp[1] End 33,264,720 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 A5 Start 40,936,398 bp[2] End 40,948,294 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • chaperone binding • GO:0001948 protein binding • adenyl-nucleotide exchange factor activity • ubiquitin protein ligase binding Cellular component • cytoplasm • cytosol • cell nucleus Biological process • regulation of cellular response to heat • cell surface receptor signaling pathway • negative regulation of apoptotic process • apoptotic process • GO:0048552 regulation of catalytic activity • chaperone mediated protein folding requiring cofactor Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	573	12017
Ensembl	ENSG00000107262	ENSMUSG00000028416
UniProt	Q99933	Q60739
RefSeq (mRNA)	NM_004323 NM_001172415 NM_001349286 NM_001349299	NM_001171739 NM_009736
RefSeq (protein)	NP_001165886 NP_004314 NP_001336215 NP_001336228	NP_001165210 NP_033866
Location (UCSC)	Chr 9: 33.25 – 33.26 Mb	Chr 4: 40.94 – 40.95 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

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.[7]

Interactions

BAG1 has been shown to interact with:

• Androgen receptor,[8][9][10]
• C-Raf,[11]
• Calcitriol receptor,[12]
• Glucocorticoid receptor,[13][14]
• HSPA8,[15][16]
• HBEGF,[17]
• PPP1R15A,[18]
• NR1B1,[19] and
• SIAH1.[20]

References

1. GRCh38: Ensembl release 89: ENSG00000107262 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028416 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: BAG1 BCL2-associated athanogene".
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.

External links

• Human BAG1 genome location and BAG1 gene details page in the UCSC Genome Browser.

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. doi:10.1002/j.1460-2075.1996.tb01009.x. 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.