protein
BAG family molecular chaperone regulator 5
aka BAG-5
Gene
BAG5
Organism
Homo sapiens(9606)
Length
447 aa
Mass
51,200 Da
BAG5 (BAG family molecular chaperone regulator 5) is a co-chaperone protein that acts as a nucleotide-exchange factor for HSP70 family chaperones, promoting the release of ADP and thereby activating HSP70-mediated protein refolding (UniProt: Q9UL15). The protein maintains proteostasis at junctional membrane complexes and inhibits parkin-mediated ubiquitination, playing roles in both protein quality control and mitochondrial dynamics.
BAG5 is expressed across tissues and has been associated with autosomal recessive dilated cardiomyopathy (CMD2F, MIM 619747) in UniProt curated disease records (UniProt: Q9UL15). Its function in chaperone-mediated proteostasis suggests broader relevance to neurodegenerative contexts.
In Alzheimer's disease, BAG5 is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.96. This reduction was detected in a single subcellular fraction using TMT-labeled quantitative proteomics, suggesting potential impairment of HSP70-dependent protein refolding capacity in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
-0.960
S3
not detected
Mean log₂FC across detected fractions: -0.9602 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding (PubMed:20223214). Has an essential role in maintaining proteostasis at junctional membrane complexes (JMC), where it may function as a scaffold between the HSPA8 chaperone and JMC proteins enabling correct, HSPA8-dependent JMC protein folding (By similarity). Inhibits both auto-ubiquitination of PRKN and ubiquitination of target proteins by PRKN (By similarity)
Disease associations
Cardiomyopathy, dilated, 2FCMD2F
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2F is an autosomal recessive, early-onset form.
Sources
Last updated 5/8/2026, 6:25:53 AM