Reactome | HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol

HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol

Stable Identifier

R-HSA-5251959

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol

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Heat-shock 70kDa proteins (HSP70s) are a family of conserved, ubiquitously expressed heat-shock proteins which play important roles in protein folding and in protecting cells from stress. They possess three functional domains; an N-terminal ATPase domain, a substrate binding domain and a C-terminal domain. HSP70s are bound to either ATP or ADP. In the ATP-bound state, HSP70s do not interact with a substrate peptide as the C-terminal domain (which acts as a lid) is "open", allowing peptides to bind to the substrate binding domain but then be released very rapidily. However, a substrate peptide in the binding domain can stimulate the intrinsic ATPase activity of HSP70s, hydrolysing ATP to ADP. With ADP bound, the C-terminal domain of HSP70s closes around the peptide, effectively trapping the peptide.

Intrinsic ATPase activity proceeds relatively slowly but can be dramatically increased by binding of J-domain chaperones such as HSP40s. These are eukaryotic orthologues of the DnaJ cochaperones found in prokaryotes. The human HSP40s that are able to modulate intrinsic ATPase activity of HSP70s are DNAJB1, B6, C2 and C7 (Raabe & Manley 1991, Melville et al. 1999, Hanai & Mashima 2003, Izawa et al. 2000, Hundley et al. 2005, Brychzy et al. 2003). They are also able to co-localise to the nucleus with HSP70s upon heat-shock (Hattori et al. 1992).

Literature References

PubMed ID	Title	Journal	Year
12974469	Characterization of two isoforms of a human DnaJ homologue, HSJ2 Hanai, R, Mashima, K	Mol. Biol. Rep.	2003
12853476	Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system Brychzy, A, Rein, T, Winklhofer, KF, Hartl, FU, Young, JC, Obermann, WM	EMBO J.	2003
9920933	The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity Melville, MW, Tan, SL, Wambach, M, Song, J, Morimoto, RI, Katze, MG	J. Biol. Chem.	1999
1586970	Intracellular localization and partial amino acid sequence of a stress-inducible 40-kDa protein in HeLa cells Hattori, H, Liu, YC, Tohnai, I, Ueda, M, Kaneda, T, Kobayashi, T, Tanabe, K, Ohtsuka, K	Cell Struct. Funct.	1992
1754405	A human homologue of the Escherichia coli DnaJ heat-shock protein Raabe, T, Manley, JL	Nucleic Acids Res.	1991
15802566	Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous Hundley, HA, Walter, W, Bairstow, S, Craig, EA	Science	2005
10954706	Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein Izawa, I, Nishizawa, M, Ohtakara, K, Ohtsuka, K, Inada, H, Inagaki, M	J. Biol. Chem.	2000