UniProt ID: Q90473 |
FUNCTION: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. Substrate recognition component in chaperone- mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2. KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded. {ECO:0000250|UniProtKB:P11142}. SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11142}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P11142}. Cell membrane {ECO:0000250|UniProtKB:P11142}. Lysosome membrane {ECO:0000250|UniProtKB:P11142}; Peripheral membrane protein {ECO:0000250|UniProtKB:P11142}; Cytoplasmic side {ECO:0000250|UniProtKB:P11142}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock. {ECO:0000250|UniProtKB:P11142}. DOMAIN: The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide- binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins. {ECO:0000250|UniProtKB:P11142}. SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}. |
UniProt ID: Q6NYR4 |
SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000256|ARBA:ARBA00007381, ECO:0000256|RuleBase:RU003322}. |
This information was provided by UniProt through a collaboration with ZFIN. (1) |