BAG1

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; OMA:BAG1 - orthologs
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 Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva sperm apex of heart olfactory zone of nasal mucosa right auricle of heart right testis left testis skin of abdomen gastrocnemius muscle skin of leg Top expressed in seminiferous tubule epithelium of stomach lacrimal gland crypt of lieberkuhn of small intestine blood mucous cell of stomach decidua right kidney muscle of thigh parotid gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function chaperone binding protein binding adenyl-nucleotide exchange factor activity ubiquitin protein ligase binding Cellular component cytoplasm cytosol nucleus Biological process regulation of cellular response to heat cell surface receptor signaling pathway negative regulation of apoptotic process apoptotic process regulation of catalytic activity chaperone cofactor-dependent protein refolding 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

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

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. S2CID   17824475.
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 in: "Old Cells Work Differently". Phys.org. March 1, 2009.
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. Bibcode:1996PNAS...93.7063W. 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. S2CID   8704191.
• 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. Bibcode:1996PNAS...93.7063W. 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) (3): 807–13. doi:10.1042/bj3280807. 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.