cd10233

Nucleotide-binding domain of HSPA1-A, -B, -L, HSPA-2, -6, -7, -8, and similar proteins; This subfamily includes human HSPA1A (70-kDa heat shock protein 1A, also known as HSP72; HSPA1; HSP70I; HSPA1B; HSP70-1; HSP70-1A), HSPA1B (70-kDa heat shock protein 1B, also known as HSPA1A; HSP70-2; HSP70-1B), and HSPA1L (70-kDa heat shock protein 1-like, also known as HSP70T; hum70t; HSP70-1L; HSP70-HOM). The genes for these three HSPA1 proteins map in close proximity on the major histocompatibility complex (MHC) class III region on chromosome 6, 6p21.3. This subfamily also includes human HSPA8 (heat shock 70kDa protein 8, also known as LAP1; HSC54; HSC70; HSC71; HSP71; HSP73; NIP71; HSPA10; the HSPA8 gene maps to 11q24.1), human HSPA2 (70-kDa heat shock protein 2, also known as HSP70-2; HSP70-3, the HSPA2 gene maps to 14q24.1), human HSPA6 (also known as heat shock 70kDa protein 6 (HSP70B') gi 94717614, the HSPA6 gene maps to 1q23.3), human HSPA7 (heat shock 70kDa protein 7 , also known as HSP70B; the HSPA7 gene maps to 1q23.3) and Saccharmoyces cerevisiae Stress-Seventy subfamily B/Ssb1p. This subfamily belongs to the heat shock protein 70 (HSP70) family of chaperones that assist in protein folding and assembly and can direct incompetent "client" proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. HSP70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). Associations of polymorphisms within the MHC-III HSP70 gene locus with longevity, systemic lupus erythematosus, Meniere's disease, noise-induced hearing loss, high-altitude pulmonary edema, and coronary heart disease, have been found. HSPA2 is involved in cancer cell survival, is required for maturation of male gametophytes, and is linked to male infertility. The induction of HSPA6 is a biomarker of cellular stress. HSPA8 participates in the folding and trafficking of client proteins to different subcellular compartments, and in the signal transduction and apoptosis process; it has been shown to protect cardiomyocytes against oxidative stress partly through an interaction with alpha-enolase. S. cerevisiae Ssb1p, is part of the ribosome-associated complex (RAC), it acts as a chaperone for nascent polypeptides, and is important for translation fidelity; Ssb1p is also a [PSI+] prion-curing factor.