The FES1/SIL1 protein family includes nucleotide exchange factors (NEFs) that are essential for protein folding and translocation processes. Members of the FES1 subfamily function as NEFs for Hsp70 chaperones, accelerating the release of ADP and enhancing the efficiency of Hsp70-mediated protein folding . The SIL1 subfamily members are involved in protein translocation and folding within the endoplasmic reticulum, acting as NEFs for the ER lumenal chaperone HSPA5 or KAR2 [, ]. Additionally, the family includes Hsp70-binding protein HPBP1, a SIL1 paralogue and FES1 orthologue, that inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding []and with ubiquitination and chaperone-assisted degradation of proteins [].
This domain is found at the C-terminal end of human Hypoxia up-regulated protein 1 (HYOU1). This domain also covers the C-terminal in Heat shock proteins such as Heat shock protein 105 kDa, Heat shock 70 kDa protein 4 and Heat shock 70 kDa protein 14. This domain may adopt a tri-helical bundle fold.HYOU1 has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. It may play a role as a molecular chaperone and participate in protein folding [].Heat shock protein 105 kD acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release [].
