HSPA8/HSC70 Protein, Human (P. pastoris, His)

HSPA8/HSC70, a molecular chaperone, is intricately involved in diverse cellular processes, including proteome protection from stress, facilitation of polypeptide folding and transport, chaperone-mediated autophagy, activation of misfolded protein proteolysis, and modulation of protein complex formation and dissociation. Central to the protein quality control system, it ensures correct protein folding, refolding of misfolded proteins, and regulates protein targeting for subsequent degradation. This function is orchestrated through cycles of ATP binding, ATP hydrolysis, and ADP release, facilitated by co-chaperones. The nucleotide-bound state of HSP70 regulates its affinity for polypeptides, with ATP-bound form having low substrate affinity, and a conformational change upon ATP hydrolysis increasing the affinity for substrates. Co-chaperones, including J-domain co-chaperones (HSP40s), nucleotide exchange factors (NEFs) such as BAG1/2/3, and TPR domain chaperones like HOPX and STUB1, play specific roles in modulating HSP70 activity. Beyond its fundamental role in mitochondrial import, HSPA8/HSC70 also acts as a repressor of transcriptional activation, participates in the spliceosome assembly, and plays a role in selective protein degradation processes, including chaperone-mediated autophagy and ER-associated degradation. Additionally, it interacts with the VGF-derived peptide TLQP-21, indicating its involvement in diverse cellular pathways.