HSPA8 gene

The HSPA8 gene (HSPA8 stands for: Heat Shock Protein Family A (Hsp70) Member 8 is a protein-coding gene located on chromosome 11q24.1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

The HSPA8 gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. The encoded protein, a chaperone, is also known as a cognate heat shock protein. It binds to nascent polypeptides to facilitate the correct folding of these proteins. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during the transport of membrane components through the cell.

The encoded HSPA8 protein acts as a repressor of transcriptional activation. Binds bacterial lipopolysaccharide (LPS) and mediates the LPS-induced inflammatory response, including TNF secretion by monocytes (Yahata T et al. 2000). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates the degradation of proteins with a KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins with a KFERQ motif and promotes their recruitment to the surface of the lysosome, where they bind to the lysosomal protein LAMP2 (Chiang HL et al. 1989). Interacts with the VGF-derived peptide TLQP-21 (Akhter S et al. 2017).

Diseases associated with HSPA8 include auditory system disorders and Borna disease.

1. Akhter S et al. (2017) The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa protein 8 (HSPA8)on the surface of SH-SY5Y cells. PLoS One 12:e0185176.
2. Chiang HL et al. (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246:382-385.
3. Yahata T et al.(2000) The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J Biol Chem 275:8825-8834.