The human HSPA8 gene includes nine exons and eight introns. It is mapped into chromosome 11, 11q23.3-q25 (Sonna et al., 2002). Introns 5, 6 and 8 contain highly conserved repeats about 90 bp which code for U14 snoRNA (Chen et al., 1996). Exons 2, 3, 6, 7, and 9 code for the peptides of extremely uniform length, between 61 and 69 amino acids while exons 4, 8 and 5 code for peptides of 51, 78 and 185 amino acids, respectively. Two 150 bp direct repeats (nt 674 to nt 829 and nt 1783 to nt 1937) are 85% homologous to each other (Dworniczak and Mirault, 1987).

The gene coding for HSC70, HSPA8 affects the posttranscriptional silencing mediated by RNAi and is a component of the RNAi pathway in Drosophila cultured cells (Dorner et al., 2006). The promoter region of the HSPa8 gene includes a TATA box, two CCAAT boxes, two SP1 elements and two sets of heat shock response elements (HSE) where the heat shock transcriptional factors bind (Chen et al., 2002).

The HSPA8 gene coding for the protein HSC70, also known as HSP73, is a 73 kDa heat shock cognate protein. HSC70 is an ATP binding chaperone and has intrinsic ATPase activity which hydrolyzes ATP into ADP (Jakob et al., 1996). HSC70 hydrolyzing ATP initiates the conformational change of HSC70 and further causes substrate binding by HSC70 (Sullivan and Pipas, 2002).

HSC70, also called HSP73, is a 73 kDa heat shock cognate protein. The basic structure of human HSC70 includes three parts: a 44 kDa amino-terminal adenosine triphosphatase (ATPase) domain (residues 1-384), also known as the ATP-binding domain, an 18 kDa peptide (substrate) binding domain (residues 385-543), and a 10 kDa carboxyl-terminal domain (residues 544-646) which is also designated as the variable or "lid" domain (Smith et al., 1998; Tsukahara et al., 2000; Sullivan and Pipas, 2002). The carboxyl-terminal amino acid sequence Glu-Glu-Val-Asp (EEVD motif), which is absolutely conserved in all eukaryotic HSC70 and HSP70 family members, is essential for association with some co-chaperones (Mosser et al., 2000). Two amino acid sequences have the characteristics of nuclear localization signals in human HSC70 which are involved in nuclear import of HSC70: DAKRL69-73 in the amino-terminal and KRKHKKDISENKRAVRR246-262 in the ATPase domain (Lamian et al., 1996; Tsukahara and Maru, 2004).

Various conditions and molecules can affect the expression of the HSPA8 gene. The table below summarizes the factors which affect the expression of the HSPA8 gene (Liu et al., 2012).

HSC70 is a major cytosolic molecular chaperone (Place and Hofmann, 2005). However, HSC70 is also located in various cellular locations such as nuclear and close to cellular membrane (Arispe et al., 2002). HSC70 can interact with the lipid bilayer in the cellular membrane directly and form ion-conductance channels allowing ion flow through the cellular membrane. HSC70 is also identified as a tyrosine-phosphorylated protein associated with the nuclear envelope. HSC70 supports the nuclear import of karyophilic proteins and may play a role in nucleocytoplasmic transport (Otto et al., 2001).

1. As a molecular chaperone, HSC70 regulates protein folding, maintains protein normal structure and functions, and protects cells from physical and chemcial damage. HSC70 regulates protein maturation and interacts with nascent polypeptides in the process of new protein synthesis (Beckmann et al., 1990; Beckmann et al.,1992). HSC70 can also regulate the translocation of proteins into different cellular organelles such as endoplasmic reticulum and mitochondria (Chirico et al., 1998, Sheffield et al., 1990).
2. HSC70 was oginally characterized as an uncoating ATPase that dissociates clathrin triskelions from clathrin-coated vesicles. It catalyzes the ATP-dependent uncoating of clathrin-coated pits (chappell et al., 1986; Goldfarb et al., 2005).
3. HSC70 is involved in targeting protein to lysosomes for degradation (Terlecky et al., 1992) and to ubiquitin/proteasome machinery for degradation (Massyuki, 1994).
4. HSC70 regulates cellular signaling and functions such as steroid receptor maturation and Akt signaling pathway (Kimmins and MacRae, 2000; Shiota et al., 2010).
5. HSC70 is important in regulating apoptosis, embryonic development and aging (Beere, 2004; Sreedhar and Csermely, 2004; Kodiha et al., 2005).

HSC70 belongs to the HSP70 family in which includes other three members: the HSP70, the glucose-regulated protein 78 (GRP78), and HSP75. Human HSC70 shares 85% amino acid similarity with HSP70 (Ali et al., 2003). They have similar functions and interact with each other in an ATP-dependent manner. HSC70 can form a stable complex with newly synthesized HSP70 upon heat shock (Brown et al., 1993).