STCH ENCODES THE ATPASE CORE OF A MICROSOMAL STRESS70 PROTEIN

The stress70 protein chaperone family plays a central role in the proc essing of cytosolic and secretory proteins. We have cloned a human cDN A, designated Stch, that is conserved in rat tissues and which encodes a novel microsome-associated member of the stress70 protein chaperone family. Stch mRNA is constitutively expressed in all human cell types and is induced by incubation with the calcium ionophore A23187, but n ot by exposure to heat shock. Inspection of the predicted amino acid s equence reveals that the STCH product contains a unique hydrophobic le ader sequence and shares homology within the amino terminal domains of the stress70 gene family, but has a 50 residue insertion within the A TP-binding domains and truncates the carboxyl terminal peptide-binding region. Immunofluorescent and subcellular analyses show that STCH mig rates predominantly as a 60 kDa species and is enriched in a membrane- bound microsome fraction. In contrast to purified BiP and dnaK, howeve r, STCH demonstrates ATPase activity that is independent of peptide st imulation. Stch, therefore, encodes a calcium-inducible, microsome-ass ociated ATPase activity with properties similar to a proteolytically c leaved N-terminal HSC70/BiP fragment. This truncated stress70 molecule may allow increased diversity in cellular responses to protein proces sing requirements.