DNAJB6
Domain
Isoform B
The antiaggregation activity of isoform B resides in the serine-rich region and the C-terminus.
Function
Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70 (PubMed:10954706, PubMed:28233300). Plays an indispensable role in the organization of KRT8/KRT18 filaments (PubMed:10954706). Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin (PubMed:11896048, PubMed:22366786). Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins (PubMed:20159555, PubMed:22366786). Also reduces cellular toxicity and caspase-3 activity (PubMed:11896048).
Isoform B
Isoform B but not isoform A inhibits huntingtin aggregation.
Involvement in disease
Muscular dystrophy, limb-girdle, autosomal dominant 1
LGMDD1
An autosomal dominant myopathy characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region.
None
The disease is caused by variants affecting the gene represented in this entry. There is evidence that LGMDD1 is caused by dysfunction of isoform B (PubMed:22366786).
Tissue Specificity
Widely expressed. Highest levels in testis and brain, and lower levels in heart, spleen, intestine, ovary, placenta, lung, kidney, pancreas, thymus, prostate, skeletal muscle, liver and leukocytes. In testis, expressed in germ cells in the earlier stages of differentiation pathway as well as in spermatids. In brain, expressed at a higher level in hippocampus and thalamus and a lower level in amygdala, substantia nigra, corpus callosum and caudate nucleus.
Cellular localization
- Cytoplasm
- Perinuclear region
- Nucleus
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
Alternative names
HSJ2, MRJ, MSJ1, DNAJB6, DnaJ homolog subfamily B member 6, HHDJ1, Heat shock protein J2, MSJ-1, HSJ-2