DNAJB2 Antibody - #DF10101

Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family. In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins. 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. Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins.

Ubiquitinated by STUB1; does not lead to proteasomal degradation.

Cytoplasm. Nucleus.

Endoplasmic reticulum membrane>Lipid-anchor>Cytoplasmic side.

More abundantly expressed in neocortex, cerebellum, spinal cord and retina where it is expressed by neuronal cells (at protein level). Detected at much lower level in non-neuronal tissues including kidney, lung, heart, skeletal muscle, spleen and testis (at protein level). Isoform 1 is more abundant in neocortex and cerebellum compared to isoform 2 (at protein level).

Interacts with HSP70 (HSPA1A or HSPA1B). Interacts with HSPA8/Hsc70. Interacts with PSMA3 and most probably with the whole proteasomal complex.

The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity (PubMed:22219199). The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3 (PubMed:21625540). The J domain is required to reduce PRKN cytoplasmic aggregation (PubMed:20889486).

The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome (PubMed:15936278). The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation (PubMed:21625540). The UIM domains are not required to reduce PRKN cytoplasmic aggregation (PubMed:20889486).