Search Results
Overview
| Uniprot ID | P63017 |
|---|---|
| Protein Name | Heat shock cognate 71 kDa protein |
| Gene Name | Hspa8 |
| Organism | Mus musculus |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 108 | PKVQVEYKGETKSFY |
| 500 | KSTGKENKITITNDK |
| 507 | KITITNDKGRLSKED |
| 512 | NDKGRLSKEDIERMV |
| 601 | HQQKELEKVCNPIIT |
| 71 | TNTVFDAKRLIGRRF |
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, formation and dissociation of protein complexes, and antigen presentation (PubMed:30718432). 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 of HSP70, 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 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. The HSP70-associated 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. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. 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. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. 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 (PubMed:30718432). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:30718432). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0032279 | asymmetric synapse |
| Molecular Function | GO:0005102 | signaling receptor binding |
| Molecular Function | GO:0031625 | ubiquitin protein ligase binding |
| Molecular Function | GO:0051082 | unfolded protein binding |
| Biological Process | GO:0046034 | ATP metabolic process |
| Biological Process | GO:0071276 | cellular response to cadmium ion |
| Biological Process | GO:0034605 | cellular response to heat |
| Biological Process | GO:0070301 | cellular response to hydrogen peroxide |
| Biological Process | GO:0021549 | cerebellum development |
| Biological Process | GO:0061684 | chaperone-mediated autophagy |
| Biological Process | GO:1904764 | chaperone-mediated autophagy translocation complex disassembly |
| Biological Process | GO:0072318 | clathrin coat disassembly |
| Biological Process | GO:0006351 | DNA-templated transcription |
| Biological Process | GO:0044849 | estrous cycle |
| Biological Process | GO:0030900 | forebrain development |
| Biological Process | GO:0000082 | G1/S transition of mitotic cell cycle |
| Biological Process | GO:0044829 | host-mediated activation of viral genome replication |
| Biological Process | GO:0044788 | host-mediated perturbation of viral process |
| Biological Process | GO:0001822 | kidney development |
| Biological Process | GO:0061738 | late endosomal microautophagy |
| Biological Process | GO:0098880 | maintenance of postsynaptic specialization structure |
| Biological Process | GO:0000398 | mRNA splicing, via spliceosome |
| Biological Process | GO:0010667 | negative regulation of cardiac muscle cell apoptotic process |
| Biological Process | GO:0045892 | negative regulation of DNA-templated transcription |
| Biological Process | GO:1900226 | negative regulation of NLRP3 inflammasome complex assembly |
| Biological Process | GO:1902904 | negative regulation of supramolecular fiber organization |
| Biological Process | GO:0043085 | positive regulation of catalytic activity |
| Biological Process | GO:0030335 | positive regulation of cell migration |
| Biological Process | GO:0160020 | positive regulation of ferroptosis |
| Biological Process | GO:0010628 | positive regulation of gene expression |
| Biological Process | GO:0097214 | positive regulation of lysosomal membrane permeability |
| Biological Process | GO:0048026 | positive regulation of mRNA splicing, via spliceosome |
| Biological Process | GO:0050766 | positive regulation of phagocytosis |
| Biological Process | GO:1904592 | positive regulation of protein refolding |
| Biological Process | GO:0045862 | positive regulation of proteolysis |
| Biological Process | GO:0001916 | positive regulation of T cell mediated cytotoxicity |
| Biological Process | GO:0046777 | protein autophosphorylation |
| Biological Process | GO:0030163 | protein catabolic process |
| Biological Process | GO:0006457 | protein folding |
| Biological Process | GO:0006606 | protein import into nucleus |
| Biological Process | GO:0042026 | protein refolding |
| Biological Process | GO:0061740 | protein targeting to lysosome involved in chaperone-mediated autophagy |
| Biological Process | GO:0044743 | protein transmembrane import into intracellular organelle |
| Biological Process | GO:0032984 | protein-containing complex disassembly |
| Biological Process | GO:0051726 | regulation of cell cycle |
| Biological Process | GO:0099175 | regulation of postsynapse organization |
| Biological Process | GO:0061635 | regulation of protein complex stability |
| Biological Process | GO:0031647 | regulation of protein stability |
| Biological Process | GO:0014823 | response to activity |
| Biological Process | GO:0032355 | response to estradiol |
| Biological Process | GO:0045471 | response to ethanol |
| Biological Process | GO:0010045 | response to nickel cation |
| Biological Process | GO:1990834 | response to odorant |
| Biological Process | GO:0032570 | response to progesterone |
| Biological Process | GO:0042594 | response to starvation |
| Biological Process | GO:0009410 | response to xenobiotic stimulus |
| Biological Process | GO:0007519 | skeletal muscle tissue development |
| Biological Process | GO:1990832 | slow axonal transport |
| Cellular Component | GO:0005776 | autophagosome |
| Cellular Component | GO:0030424 | axon |
| Cellular Component | GO:0009986 | cell surface |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0030425 | dendrite |
| Cellular Component | GO:0043198 | dendritic shaft |
| Cellular Component | GO:0043197 | dendritic spine |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005615 | extracellular space |
| Cellular Component | GO:0098978 | glutamatergic synapse |
| Cellular Component | GO:0098690 | glycinergic synapse |
| Cellular Component | GO:0005882 | intermediate filament |
| Cellular Component | GO:0005770 | late endosome |
| Cellular Component | GO:0031906 | late endosome lumen |
| Cellular Component | GO:1990836 | lysosomal matrix |
| Cellular Component | GO:0005765 | lysosomal membrane |
| Cellular Component | GO:0042470 | melanosome |
| Cellular Component | GO:0005874 | microtubule |
| Cellular Component | GO:0043209 | myelin sheath |
| Cellular Component | GO:0044309 | neuron spine |
| Cellular Component | GO:0043025 | neuronal cell body |
| Cellular Component | GO:0005730 | nucleolus |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0043204 | perikaryon |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0001917 | photoreceptor inner segment |
| Cellular Component | GO:0098684 | photoreceptor ribbon synapse |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0098794 | postsynapse |
| Cellular Component | GO:0014069 | postsynaptic density |
| Cellular Component | GO:0099634 | postsynaptic specialization membrane |
| Cellular Component | GO:0098793 | presynapse |
| Cellular Component | GO:0101031 | protein folding chaperone complex |
| Cellular Component | GO:0032991 | protein-containing complex |
| Cellular Component | GO:0000974 | Prp19 complex |
| Cellular Component | GO:1990904 | ribonucleoprotein complex |
| Cellular Component | GO:0005681 | spliceosomal complex |
| Cellular Component | GO:0008021 | synaptic vesicle |
| Cellular Component | GO:0043195 | terminal bouton |
| Molecular Function | GO:0031686 | A1 adenosine receptor binding |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0016887 | ATP hydrolysis activity |
| Molecular Function | GO:0140545 | ATP-dependent protein disaggregase activity |
| Molecular Function | GO:0055131 | C3HC4-type RING finger domain binding |
| Molecular Function | GO:1990833 | clathrin-uncoating ATPase activity |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:0001664 | G protein-coupled receptor binding |
| Molecular Function | GO:0031072 | heat shock protein binding |
| Molecular Function | GO:0042277 | peptide binding |
| Molecular Function | GO:0001786 | phosphatidylserine binding |
| Molecular Function | GO:1904593 | prostaglandin binding |
| Molecular Function | GO:0044183 | protein folding chaperone |
| Molecular Function | GO:0051087 | protein-folding chaperone binding |
| Molecular Function | GO:0030674 | protein-macromolecule adaptor activity |
| Molecular Function | GO:0048018 | receptor ligand activity |
| Molecular Function | GO:0003723 | RNA binding |
Reference
[1] Chang J, Wu W, Qian P, Lu Z, He X et al.. Multi-omics study on the effect of moderate-intensity exercise on protein lactylation in mouse muscle tissue.. Front Cell Dev Biol 12:1472338. 2024. PMID: 39935788.
[2] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.