Starts at 127036953 bp and ends at 127043430 bp from pter.

The gene is constitutively expressed in all nucleated cells. Under cellular stress conditions (such as hypoxia or glucose starvation) transcritption is upregulated via the "unfolded protein response" (UPR).

Four pseudogenes were reported (human pseudogenes from protein P11021).

HspA5 (heat shock protein A5), also termed immunoglobulin heavy chain binding protein (BiP) or glucose regulated protein with an apparent mass of 78 kDa (Grp78) is a Hsp70-type molecular chaperone of the endoplasmic reticulum (ER).

The protein is synthesized as a precursor with an aminoterminal signal peptide of 18 amino acid residues that directs the precursor into the ER. The mature protein (i.e. after removal of the signal peptide by signal peptidase in the ER) contains 635 amino acid residues, including a carboxyterminal ER retention motif that comprises four amino acid residues (KDEL).

The HSPA5 gene is expressed in all nucleated cells, in particular in thyroid-, lung-, smooth muscle-, liver-, and various cells of the immune system. Under cellular stress conditions the gene is over-expressed due to UPR.

HspA5/BiP is a resident protein of the endoplasmic reticulum (ER). Typically, it is a soluble protein of the lumen of the ER. However, a subfraction of HspA5/BiP can be found on the cell surface of certain cell types, in particular of cancer cells.

The ER is involved in a variety of essential and interconnected processes, including protein biogenesis (protein transport into the ER, protein folding and assembly, and ER associated protein degradation), signal transduction (unfolded protein response/UPR), and calcium homeostasis. The central player in all these processes is the molecular chaperone HspA5/BiP. HspA5/BiP crucially depends on a number of interaction partners, including co-chaperones (ERj1 through ERj7), nucleotide exchange factors (Sil1, Grp170), other chaperones (calnexin, calreticulin, Grp94, UGGT), folding catalysts (protein disulfide isomerases/PDI, and peptidyl prolyl cis/trans isomerases such as Cyclophilin B) and signaling molecules (IRE1, ATF6, PERK, Sigma-1 receptor).
As a typical Hsp70, HspA5/BiP comprises an aminoterminal nucleotide binding domain and a carboxyterminal substrate (poly)peptide binding domain. Its functional cycle involves an ATP-form with low affinity for substrate (poly)peptides and an ADP-form with high substrate affinity and is regulated by Hsp40-type co-chaperones and nucleotide exchange factors.
Molecular chaperones of the Hsp70 type family reversibly bind to substrate polypeptides via the substrate binding domain (SBD). Typically, Hsp70 substrates are hydrophobic oligopeptides within more or less unfolded polypeptides. The binding of a substrate to the SBD inhibits unproductive interactions of the polypeptide and favors productive folding and assembly that occur concomitant with release from Hsp70. In addition, Hsp70s can regulate the activities of folded polypeptides.

HspA5/BiP belongs to the heat shock protein 70 (Hsp70) family of molecular chaperones. As such it is structurally related to the cytosolic Hsp70s (Hsc70, Hsp70.1, Hsp70.3, Hsp70L1) and the mitochondrial Hsp70 (Grp75/mtHsp75). In addition, HspA5/BiP is structurally related to its nucleotide exchange factor Grp170 that also belongs to the Hsp70 protein family.

Not known.

Not known.