Reactome | FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein

FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein

Stable Identifier

R-HSA-5618085

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein

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FKBP52 (also known as the large immunophilin FKBP4) is a co-chaperone containing tetratricopeptide repeat (TPR) domain, which binds the C-terminal sequence motif (MEEVD) of HSP90 (Wu B et al. 2004; Davies and Sanchez 2005). The stoichiometry of FKBP in receptor heterocomplexes was determined on the basis of the size of cross-linked complexes, a ratio of one molecule of receptor and two molecules of HSP90 to one molecule of FKBP52 was obtained for human PR , ER and mouse GR (Rexin M et al. 1992; Rehberger P et al. 1992; Segnitz B and Gehring U 1995). Mass spectrometry analysis showed that FKBP51 (FKBP5) and FKBP52 (FKBP4) form analogous complexes with GR:HSP90:STIP1:HSP70:ATP (Ebong IO et al. 2016). Binding of FKBP52 (FKBP4) and other immunophilins may weaken the association of TPR domain containing protein STIP1 with HSP90 complex (Li et al. 2011).

FKBP52 (FKBP4) is a member of the immunophilin (IMM) protein family of intracellular proteins that are able to bind immunosuppressant drugs, from which the term immunophilin derives (Pratt and Toft 1997; Kang et al. 2008). These proteins are also known as peptidyl-prolyl cis/trans isomerases (PPIases) for their ability to convert proline bonds from cis to trans form, a rate-limiting step in protein folding (Harding et al. 1989; Standaert et al. 1990; Galat 2003; Davies and Sanchez 2005). In addition to the PPIase and TPR domains, there are two additional domains - the nucleotide-binding domain (also called FKBD2 in FKBP proteins) where ATP binds and the calmodulin-binding domain, a poorly characterized domain able to interact with calmodulin.

Literature References

PubMed ID	Title	Journal	Year
18635947	FKBP family proteins: immunophilins with versatile biological functions Kang, CB, Hong, Y, Dhe-Paganon, S, Yoon, HS	Neurosignals	2008
15381148	FKBP52 Davies, TH, Sánchez, ER	Int. J. Biochem. Cell Biol.	2005
15159550	3D structure of human FK506-binding protein 52: implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex Wu, B, Li, P, Liu, Y, Lou, Z, Ding, Y, Shu, C, Ye, S, Bartlam, M, Shen, B, Rao, Z	Proc. Natl. Acad. Sci. U.S.A.	2004