DNAJB2

This gene is almost exclusively expressed in the brain, mainly in the neuronal layers. It encodes a protein that shows sequence similarity to bacterial DnaJ protein and the yeast homologs. In bacteria, this protein is implicated in protein folding and protein complex dissociation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

Full Name

DnaJ Heat Shock Protein Family (Hsp40) Member B2

Function

Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:7957263, PubMed:22219199).

In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540).

Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695).

Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278).

Biological Process

Chaperone-mediated protein folding Source: UniProtKB
Negative regulation of cell growth Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of inclusion body assembly Source: BHF-UCL
Negative regulation of protein binding Source: UniProtKB
Negative regulation of protein deubiquitination Source: BHF-UCL
Neuron cellular homeostasis Source: ARUK-UCL
Positive regulation of ATPase activity Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
Positive regulation of protein ubiquitination Source: BHF-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein refolding Source: UniProtKB
Regulation of chaperone-mediated protein folding Source: UniProtKB
Regulation of protein localization Source: ParkinsonsUK-UCL
Regulation of protein ubiquitination Source: UniProtKB
Response to unfolded protein Source: ProtInc
Ubiquitin-dependent ERAD pathway Source: BHF-UCL

Cellular Location

Isoform 1: Endoplasmic reticulum membrane
Isoform 2: Cytoplasm; Nucleus

Involvement in disease

Distal spinal muscular atrophy, autosomal recessive, 5 (DSMA5):
An autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired.

PTM

Ubiquitinated by STUB1; does not lead to proteasomal degradation.