DNAJB14
Description
The DNAJB14 (DnaJ heat shock protein family (Hsp40) member B14) is a protein-coding gene located on chromosome 4.
DNAJB14 (DnaJ homolog subfamily B member 14) is a protein that in humans is encoded by the DNAJB14 gene. It acts as a co-chaperone with HSPA8/Hsc70 and is required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway. It acts by determining HSPA8/Hsc70's ATPase and polypeptide-binding activities. It can also act independently of HSPA8/Hsc70: together with DNAJB12, it acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers. While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70. When overexpressed, it forms membranous structures together with DNAJB12 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear. In case of infection by polyomavirus, it is involved in the virus endoplasmic reticulum membrane penetration and infection. It interacts (via J domain) with HSPA8/Hsc70. It forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct.
DNAJB14 is a co-chaperone that works with HSPA8/Hsc70. It helps in protein folding and trafficking, preventing protein aggregation and promoting the breakdown of misfolded proteins through the ERAD pathway. DNAJB14 influences HSPA8/Hsc70's ability to bind to ATP and polypeptides. It can also act independently of HSPA8/Hsc70, working with DNAJB12 to assist in the maturation of potassium channels KCND2 and KCNH2. This involves stabilizing newly formed channel subunits and assembling them into functional tetramers. While HSPA8/Hsc70 is crucial for stabilizing these nascent channel proteins, the process of assembling the subunits into oligomers does not require HSPA8/Hsc70. When present in excess, DNAJB14 forms membranous structures within the nucleus, along with DNAJB12 and HSPA8/Hsc70. These structures, known as DJANGOs, have an unknown function.
DNAJB14 is also known as EGNR9427, PRO34683.
Associated Diseases
- isolated asymptomatic elevation of creatine phosphokinase
- plasma fibronectin deficiency
- pentosuria
- autosomal recessive hypophosphatemic rickets
- myopathy due to calsequestrin and SERCA1 protein overload
- metabolic myopathy due to lactate transporter defect
