InterPro domain: IPR039981

This entry includes a group of heat shock protein interacting proteins, including AHSA1/2 from animals and Aha1/Hch1 from budding yeasts.

Activator of 90kDa heat shock protein ATPase (AHSA1/p38, O95433 ) is known to interact with the middle domain of Hsp90, and stimulate its ATPase activity [ 1 ]. It is probably a general up regulator of Hsp90 function, particularly contributing to its efficiency in conditions of increased stress [ 2 ]. It is also known to interact with the cytoplasmic domain of the VSV G protein, and may thus be involved in protein transport [ 3 ]. It has also been reported as being under expressed in Down's syndrome. This region is found repeated in two members of this family ( Q8XY04 and Q6MH87 ).

In budding yeasts, both Hch1 and Aha1 bind to the middle domain of Hsp90 and stimulate ATPase activity [ 4 , 4 ]. However, Aha1 but not Hch1 stimulated the intrinsic ATPase activity of Hsp90 5-fold [ 5 ]. Hch1 and Aha1 may regulate Hsp90 function in distinct ways [ 5 ].

1. Aha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone. J. Biol. Chem. 278, 17228-35
2. Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol. Cell 10, 1307-18
3. p38: A novel protein that associates with the vesicular stomatitis virus glycoprotein. Biochem. Biophys. Res. Commun. 287, 574-82
4. Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle. Nat. Struct. Mol. Biol. 20, 326-31