HSC70 a molecular chaperone of the heat shock protein 70 family implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, 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 co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity 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. The co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. Interacts with VGF-derived peptide TLQP-21. Belongs to the heat shock protein 70 family. Ubiquitous. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Chaperone; Heat shock protein; Nucleolus; RNA-binding
Chromosomal Location of Human Ortholog: 9 A5.1|9 21.55 cM
Cellular Component:  asymmetric synapse; autophagosome; axon; cell surface; chaperone complex; cytoplasm; cytosol; dendrite; dendritic shaft; dendritic spine; extracellular exosome; glutamatergic synapse; glycinergic synapse; intermediate filament; late endosome; lysosomal matrix; lysosomal membrane; lysosome; membrane; membrane raft; messenger ribonucleoprotein complex; microtubule; neuron projection; neuron spine; neuronal cell body; nucleus; perikaryon; perinuclear region of cytoplasm; photoreceptor inner segment; photoreceptor ribbon synapse; plasma membrane; postsynapse; postsynaptic cytosol; postsynaptic density; postsynaptic specialization membrane; presynapse; presynaptic cytosol; protein-containing complex; Prp19 complex; ribonucleoprotein complex; spliceosomal complex; synaptic vesicle; terminal bouton
Molecular Function:  A1 adenosine receptor binding; ADP binding; ATP binding; ATPase activity; ATPase activity, coupled; C3HC4-type RING finger domain binding; chaperone binding; clathrin-uncoating ATPase activity; enzyme binding; G protein-coupled receptor binding; heat shock protein binding; misfolded protein binding; nucleotide binding; peptide binding; phosphatidylserine binding; prostaglandin binding; protein binding; protein binding involved in protein folding; protein binding, bridging; RNA binding; signaling receptor binding; transcription factor binding; ubiquitin protein ligase binding; unfolded protein binding
Biological Process:  ATP metabolic process; axo-dendritic transport; cellular protein complex disassembly; cellular response to heat; cellular response to unfolded protein; chaperone cofactor-dependent protein refolding; chaperone-mediated autophagy; chaperone-mediated autophagy translocation complex disassembly; chaperone-mediated protein folding; chaperone-mediated protein transport involved in chaperone-mediated autophagy; clathrin coat disassembly; late endosomal microautophagy; maintenance of postsynaptic specialization structure; modulation by host of viral process; mRNA processing; negative regulation of cardiac muscle cell apoptotic process; negative regulation of supramolecular fiber organization; negative regulation of transcription, DNA-templated; positive regulation by host of viral genome replication; positive regulation of catalytic activity; positive regulation of gene expression; positive regulation of lysosomal membrane permeability; positive regulation of mRNA splicing, via spliceosome; positive regulation of phagocytosis; positive regulation of protein refolding; positive regulation of proteolysis; positive regulation of T cell mediated cytotoxicity; protein autophosphorylation; protein folding; protein import into nucleus; protein refolding; protein targeting to lysosome involved in chaperone-mediated autophagy; regulation of cell cycle; regulation of postsynapse organization; regulation of protein complex stability; regulation of protein stability; response to unfolded protein; RNA splicing; slow axonal transport; vesicle-mediated transport
Reference #:  P63017 (UniProtKB)
Alt. Names/Synonyms: 2410008N15Rik; heat shock 70 kDa protein 8; heat shock 70kD protein 8; Heat shock cognate 71 kDa protein; heat shock cognate hsc73; heat shock protein 8; heat shock protein cognate 70; Hsc70; Hsc71; Hsc73; Hsp73; Hspa10; Hspa8; MGC102007; MGC106514; MGC118485
Gene Symbols: Hspa8
Molecular weight: 70,871 Da
Basal Isoelectric point: 5.37  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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HSC70

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein