Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stress70 protein chaperone family plays a central role in the processing of cytosolic and secretory proteins. We have cloned a human cDNA, 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 not by exposure to heat shock. Inspection of the predicted amino acid sequence reveals that the STCH product contains a unique hydrophobic leader sequence and shares homology within the amino terminal domains of the stress70 gene family, but has a 50 residue insertion within the ATP-binding domains and truncates the carboxyl terminal peptide-binding region. Immunofluorescent and subcellular analyses show that STCH migrates predominantly as a 60 kDa species and is enriched in a membrane-bound microsome fraction. In contrast to purified BiP and dnaK, however, STCH demonstrates ATPase activity that is independent of peptide stimulation. Stch, therefore, encodes a calcium-inducible, microsome-associated ATPase activity with properties similar to a proteolytically cleaved N-terminal HSC70/BiP fragment. This truncated stress70 molecule may allow increased diversity in cellular responses to protein processing requirements.
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PMID:Stch encodes the 'ATPase core' of a microsomal stress 70 protein. 813 51

We have identified the rat and Caenorhabditis elegans homologues of a 'core ATPase'-encoding Hsp70-like gene, designated Stch. We observed that the human, rat, and C. elegans Stch genes have conserved a stop codon immediately distal to the sequence encoding the Hsp70 ATPase domain. This results in the functional equivalent of an N-terminal, proteolytically cleaved fragment of Hsc70/BiP. Each homologue contains a hydrophobic signal sequence, demonstrates striking identity within the Hsp70 ATPase domain, and retains a similar C-terminal sequence (STCH specific cluster III) that is unique among Hsp70 proteins and which truncates the peptide binding domain. In addition, we have identified an internal 35-aa region that is homologous to the minimal sequence of the Hip chaperone co-factor that is required for direct binding to the ATPase domain of Hsp70. Adjacent to this region, the rat and human STCH protein sequences diverge within a short internal 'insertion' sequence that interrupts the ATPase subdomain between the phosphate-2 and adenosine ATP-binding sites. We have also demonstrated that both human and rat Stch are constitutively produced and are induced by the calcium ionophore A23187, but not by heat shock. The recognition that the truncated 'core ATPase' structure of the STCH molecule is conserved in human, rat, and C. elegans tissues suggests an important role for this unique member of the membrane-bound Hsp70 family.
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PMID:A 'core ATPase', Hsp70-like structure is conserved in human, rat, and C. elegans STCH proteins. 935 68