Fig. 2.

Hsp70s involved in protein translocation across the endoplasmic reticulum (ER) and mitochondrial membranes. Hsp70s and J-proteins of Saccharomyces cerevisiae are indicated, with the commonly used names for the orthologous proteins in human cells in parentheses. J-domains indicated by “J”. The major class of Hsp70 found in the cytosol of all eukaryotes is called Ssa or Hsc70/Hsp70 in fungi and other eukaryotes, respectively. An EEVD tetrapeptide present at the C-terminus targets these Hsp70s to interacting proteins such as receptors on organelle membranes, Hsp90 molecular chaperones, or proteolytic systems. These Hsp70s are encoded by between one and four genes in fungi, depending on the species, and by five genes (HSPA1, 2, 6, 7, 8) in humans. Fungi have another type of cytosolic Hsp70, called Ssb, which is predominately ribosome-associated. Humans have no Ssb ortholog; rather, the Hsc70/Hsp70 type performs the equivalent functions. Both Ssb and Hsp70/Hsc70 partner with a conserved, specialized J-protein, Zuo1 in fungi and Mpp11 (DNAJC2) in other eukaryotes, which is predominately ribosome-associated. Ydj1 (Hdj2 or DNAJA1 in other eukaryotes) is the most abundant J-protein partner of those cytosolic Hsp70s involved in protein translocation. In most eukaryotes, the lumen of the ER and the mitochondrial matrix have a single Hsp70, which plays multiple roles in their respective organelles, including general protein folding. ER Hsp70 is often called BiP; encoded by KAR2 (fungi) or HSPA5 (humans). Mitochondrial Hsp70 (mtHsp70) is called Ssc1 in fungi. In humans mtHsp70 is encoded by HSPA9. Some fungi have an additional Hsp70 (called Ssq1) specializing in Fe-S cluster biogenesis, and a low abundance Hsp70, Ecm10. Sec63 (ERdj2) in human cells is encoded by DNAJC23. ERJ1 (ERdj1) is not present in fungi. Pam18 (also called Tim14) of fungi has two orthologs in human cells, DNAJC17 (or Tim14) and DnajC15, sometimes called MCJ