BAG family molecular chaperone regulator 1 (BAG1)
The protein contains 345 amino acids for an estimated molecular weight of 38779 Da.
Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70 (PubMed:27474739, PubMed:9873016, PubMed:24318877). Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity (PubMed:12724406). Markedly increases the anti-cell death function of BCL2 induced by various stimuli (PubMed:9305631). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Apoptotic process
Cell surface receptor signaling pathway
Chaperone cofactor-dependent protein refolding
Chaperone cofactor-dependent protein refolding
Intracellular signal transduction
Negative regulation of apoptotic process
Protein stabilization
Regulation of cellular response to heat
The reference OMIM entry for this protein is 601497
Bcl2-associated athanogene 1; bag1
Receptor-associated protein, 46-kd; rap46
CLONING
The oncogene BCL2 (151430) is a membrane protein that blocks a step in a pathway leading to apoptosis. Takayama et al. (1995) used interaction cloning to identify Bag1, a mouse protein that binds to Bcl2. The Bag1 protein is rich in glutamic acid residues. By screening a human liver expression library with activated glucocorticoid receptor (GCCR; 138040), Zeiner and Gehring (1995) cloned BAG1, which they called RAP46. The deduced 274-amino acid protein has a calculated molecular mass of 31 kD. It had an apparent molecular mass of 46 kD by SDS-PAGE. Northern blot analysis detected a 1.4-kb Rap46 transcript in all mouse tissues examined. Takayama et al. (1996) cloned human BAG1 cDNAs from a fetal brain cDNA library using the mouse cDNA as a probe. The human cDNA encodes a predicted 274-amino acid protein, 55 residues longer at the N-terminal end than the mouse protein. The human BAG1 gene is 80% identical to the mouse gene sequence. The human protein is also highly acidic, with a pI of 5.3.GENE FUNCTION
Takayama et al. (1995) found that overexpression of recombinant Bag1 in 3T3 fibroblasts prevented them from undergoing apoptosis when deprived of serum. Zeiner and Gehring (1995) found that recombinant RAP46 interacted with activated glucocorticoid, androgen (AR; 313700), estrogen (see ESR1; 133430), and progesterone (PGR; 607311) receptors. Binding was dependent on receptor activation (i.e., release from heat shock proteins), but did not require the presence of receptor ligands. RAP46 showed a high affinity for estrogen receptor. Wang et al. (1996) stated that overproduction of BCL2 occurs frequently in human cancers and contributes to tumor radio- and chemoresistance by blocking apoptosis induced by genotoxic injury and other types of damage. Conversely, reduced levels of BCL2 have been associated with higher rates of spontaneous and inducible apoptosis in circulating lymphocytes of persons infected with HIV and some other viruses. The BCL2-interacting protein, BAG1, enhances the anti-apoptotic effects of BCL2. Like BAG1, the serine/threonine protein kinase RAF1 (164760) also cooperates with BCL2 in suppressing apoptosis. Wang et al. (1996) showed that RAF1 and BAG1 specifically interact in vitro and in yeast 2-hybrid assays. RAF1 and BAG1 proteins can also be coimmunoprecipitated from mammalian cells and from insect cells infected with recombinant baculoviruses encoding these proteins. Bardelli et al. (1996) found that BAG1 represents a link between growth factor receptors and anti-apoptotic mechanisms. They showed that BAG1 interacts with both the hepatocyte growth factor receptor (164860) and the platelet-derived growth factor receptor (173410) and, in both cases, enhances growth factor-mediated protection from apoptosis. The C-terminal region of the BAG1 protein was found to be responsible for binding to the receptors, but the entire BAG1 protein was required for protection from apoptosis. Kullmann et al. (1998) demonstrated that mammalian Rap46 bound the hinge region of the glucocorticoid receptor and inhibited DNA binding and transactivation by the receptor. Overexpression of Rap46 in mouse thymoma cells inhibited glucocorticoid-induced apoptosis. Conversely, treatment with rapamycin, a RAP46 downregulator, enhanced glucocorticoid-induced apoptosis and transactivation. Yang et al. (1999) cloned and characterized the human BAG1 gene promoter. Functional characterization of the BAG1 promoter in vivo dem ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601497 was added.