cd11739: HSPH1_NBD (this model, PSSM-Id:212689 is obsolete and has been replaced by 466845)
Nucleotide-binding domain of HSPH1
Human HSPH1 (also known as heat shock 105kDa/110kDa protein 1, HSP105; HSP105A; HSP105B; NY-CO-25; the human HSPH1 gene maps to 13q12.3) suppresses the aggregation of denatured proteins caused by heat shock in vitro, and may substitute for HSP70 family proteins to suppress the aggregation of denatured proteins in cells under severe stress. It reduces the protein aggregation and cytotoxicity associated with Polyglutamine (PolyQ) diseases, including Huntington's disease, which are a group of inherited neurodegenerative disorders sharing the characteristic feature of having insoluble protein aggregates in neurons. The expression of HSPH1 is elevated in various malignant tumors, including malignant melanoma, and there is a direct correlation between HSPH1 expression and B-cell non-Hodgkin lymphomas (B-NHLs) aggressiveness and proliferation. HSPH1 belongs to the 105/110 kDa heat shock protein (HSP105/110) subfamily of the HSP70-like family. HSP105/110s are believed to function generally as co-chaperones of HSP70 chaperones, acting as nucleotide exchange factors (NEFs), to remove ADP from their HSP70 chaperone partners during the ATP hydrolysis cycle. HSP70 chaperones assist in protein folding and assembly, and can direct incompetent "client" proteins towards degradation. Like HSP70 chaperones, HSP105/110s have an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain (SBD). For HSP70 chaperones, 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 also regulated by J-domain proteins.
Jiyao W et al.(2023). "The conserved domain database in 2023.",