protein
BAG family molecular chaperone regulator 3
aka BAG-3
Gene
BAG3
Organism
Homo sapiens(9606)
Length
575 aa
Mass
61,595 Da
BAG3 (BAG family molecular chaperone regulator 3) is a co-chaperone and adapter protein that coordinates different classes of heat shock proteins, including HSP70s and small heat shock proteins like HSPB8 (UniProt: O95817). It functions as a nucleotide-exchange factor promoting ADP release from HSP70s and subsequent client protein release, and exhibits anti-apoptotic activity through binding to both the nucleotide-binding and substrate-binding domains of HSP70 proteins.
BAG3 is broadly expressed and has roles in protein quality control and cellular stress responses. Beyond its general cellular functions, mutations in BAG3 are associated with several neuromuscular and cardiac disorders including myofibrillar myopathy 6 (MFM6), dilated cardiomyopathy (CMD1HH), distal hereditary motor neuronopathy 15 (HMND15), and Charcot-Marie-Tooth disease type 2JJ (CMT2JJ), reflecting its importance in maintaining muscle and neuronal function (UniProt: O95817).
BAG3 is significantly upregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.15 in post-mortem AD brain proteomics data (Chaparral AD proteomics). This upregulation suggests BAG3 may play a role in AD-related pathology, potentially reflecting compensatory stress response mechanisms or involvement in protein misfolding processes characteristic of neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+1.149
S3
not detected
Mean log₂FC across detected fractions: +1.1486 (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 and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g. HSPA1A/HSP70 or HSPA8/HSC70, and small heat shock proteins (sHSPs), e.g. HSPB8 (PubMed:27884606, PubMed:30559338). Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from HSP70s, thereby triggering client protein release (PubMed:27884606, PubMed:30559338). Nucleotide release is mediated via BAG3 binding to the nucleotide-binding domain (NBD) of HSP70s, whereas client release is mediated via binding to the substrate-binding domain (SBD) (PubMed:27474739, PubMed:9873016). Has anti-apoptotic activity (PubMed:10597216). Plays a role in the HSF1 nucleocytoplasmic transport (PubMed:26159920)
Disease associations
Myopathy, myofibrillar, 6MFM6
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM6 is characterized by early-onset of severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency during adolescence, and a rigid spine in some patients.
Cardiomyopathy, dilated, 1HHCMD1HH
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Neuronopathy, distal hereditary motor, autosomal dominant 15HMND15
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. Weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMND15 is an adult-onset, autosomal dominant form with incomplete penetrance. HMND15 affected individuals exhibit a slowly progressive and symmetric distal weakness and atrophy of lower limb muscles, along with absent Achille reflexes. Sensory deficits are not present.
Charcot-Marie-Tooth disease, axonal, type 2JJCMT2JJ
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2JJ is characterized by adult onset of distal sensory impairment and distal muscle weakness and atrophy predominantly affecting the lower limbs.
Sources
Last updated 5/8/2026, 6:25:50 AM