ID HSP7C_RAT Reviewed; 646 AA. AC P63018; P08109; P12225; Q4FZY7; Q62373; Q62374; Q62375; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 02-SEP-2026, entry version 182. DE RecName: Full=Heat shock cognate 71 kDa protein {ECO:0000305}; DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P11142}; DE AltName: Full=Heat shock 70 kDa protein 8; GN Name=Hspa8 {ECO:0000312|RGD:621725}; GN Synonyms=Hsc70 {ECO:0000303|PubMed:10373374}, Hsc73 GN {ECO:0000303|PubMed:3595567}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3595567; DOI=10.1002/j.1460-2075.1987.tb04850.x; RA Sorger P.K., Pelham H.R.B.; RT "Cloning and expression of a gene encoding hsc73, the major hsp70-like RT protein in unstressed rat cells."; RL EMBO J. 6:993-998(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3939319; DOI=10.1128/mcb.5.12.3476-3483.1985; RA O'Malley K., Mauron A., Barchas J.D., Kedes L.; RT "Constitutively expressed rat mRNA encoding a 70-kilodalton heat-shock-like RT protein."; RL Mol. Cell. Biol. 5:3476-3483(1985). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart, and Pituitary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 4-36; 57-71; 77-108; 127-155; 160-171; 237-246; RP 300-319; 349-357; 424-447; 452-458; 518-526; 540-550; 584-597 AND 602-609, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U., Lubec S.; RL Submitted (SEP-2007) to UniProtKB. RN [5] RP INTERACTION WITH DNAJC7. RX PubMed=10567422; DOI=10.1074/jbc.274.48.34425; RA Liu F.H., Wu S.J., Hu S.M., Hsiao C.D., Wang C.; RT "Specific interaction of the 70-kDa heat shock cognate protein with the RT tetratricopeptide repeats."; RL J. Biol. Chem. 274:34425-34432(1999). RN [6] RP INTERACTION WITH SGTA. RX PubMed=15708368; DOI=10.1016/j.abb.2004.12.020; RA Liou S.T., Wang C.; RT "Small glutamine-rich tetratricopeptide repeat-containing protein is RT composed of three structural units with distinct functions."; RL Arch. Biochem. Biophys. 435:253-263(2005). RN [7] RP STRUCTURE BY NMR OF 385-543. RX PubMed=10373374; DOI=10.1006/jmbi.1999.2776; RA Morshauser R.C., Hu W., Wang H., Pang Y., Flynn G.C., Zuiderweg E.R.P.; RT "High-resolution solution structure of the 18 kDa substrate-binding domain RT of the mammalian chaperone protein Hsc70."; RL J. Mol. Biol. 289:1387-1403(1999). CC -!- FUNCTION: Molecular chaperone implicated in a wide variety of cellular CC processes, including protection of the proteome from stress, folding CC and transport of newly synthesized polypeptides, chaperone-mediated CC autophagy, activation of proteolysis of misfolded proteins, formation CC and dissociation of protein complexes, and antigen presentation. Plays CC a pivotal role in the protein quality control system, ensuring the CC correct folding of proteins, the re-folding of misfolded proteins and CC controlling the targeting of proteins for subsequent degradation. This CC is achieved through cycles of ATP binding, ATP hydrolysis and ADP CC release, mediated by co-chaperones. The co-chaperones have been shown CC to not only regulate different steps of the ATPase cycle of HSP70, but CC they also have an individual specificity such that one co-chaperone may CC promote folding of a substrate while another may promote degradation. CC The affinity of HSP70 for polypeptides is regulated by its nucleotide CC bound state. In the ATP-bound form, it has a low affinity for substrate CC proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a CC conformational change that increases its affinity for substrate CC proteins. HSP70 goes through repeated cycles of ATP hydrolysis and CC nucleotide exchange, which permits cycles of substrate binding and CC release. The HSP70-associated co-chaperones are of three types: J- CC domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the CC nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate CC conversion of HSP70 from the ADP-bound to the ATP-bound state thereby CC promoting substrate release), and the TPR domain chaperones such as CC HOPX and STUB1. Plays a critical role in mitochondrial import, delivers CC preproteins to the mitochondrial import receptor TOMM70. Acts as a CC repressor of transcriptional activation. Inhibits the transcriptional CC coactivator activity of CITED1 on Smad-mediated transcription. CC Component of the PRP19-CDC5L complex that forms an integral part of the CC spliceosome and is required for activating pre-mRNA splicing. May have CC a scaffolding role in the spliceosome assembly as it contacts all other CC components of the core complex. Binds bacterial lipopolysaccharide CC (LPS) and mediates LPS-induced inflammatory response, including TNF CC secretion by monocytes. Substrate recognition component in chaperone- CC mediated autophagy (CMA), a selective protein degradation process that CC mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 CC specifically recognizes and binds cytosolic proteins bearing a -KFERQ CC motif and promotes their recruitment to the surface of the lysosome CC where they bind to lysosomal protein LAMP2. KFERQ motif-containing CC proteins are eventually transported into the lysosomal lumen where they CC are degraded. In conjunction with LAMP2, facilitates MHC class II CC presentation of cytoplasmic antigens by guiding antigens to the CC lysosomal membrane for interaction with LAMP2 which then elicits MHC CC class II presentation of peptides to the cell membrane. Participates in CC the ER-associated degradation (ERAD) quality control pathway in CC conjunction with J domain-containing co-chaperones and the E3 ligase CC STUB1. It is recruited to clathrin-coated vesicles through its CC interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase CC activity and therefore uncoating of clathrin-coated vesicles (By CC similarity). {ECO:0000250|UniProtKB:P11142, CC ECO:0000250|UniProtKB:P19120}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10; CC Evidence={ECO:0000250|UniProtKB:P11142}; CC -!- SUBUNIT: Component of the chaperone-assisted selective autophagy (CASA) CC complex consisting of BAG3, HSPA8/HSC70, HSPB8 and STUB1/CHIP (By CC similarity). Identified in a IGF2BP1-dependent mRNP granule complex CC containing untranslated mRNAs (By similarity). Interacts with PACRG (By CC similarity). Interacts with HSPH1/HSP105 (By similarity). Interacts CC with IRAK1BP1 and BAG1 (By similarity). Interacts with DNAJC7 CC (PubMed:10567422). Interacts with DNAJB12 (via J domain) (By CC similarity). Interacts with DNAJB14 (via J domain) (By similarity). CC Interacts (via C-terminus) with the E3 ligase STUB1 forming a 210 kDa CC complex of one STUB1 and two HSPA8 molecules (By similarity). Interacts CC with CITED1 (via N-terminus); the interaction suppresses the CC association of CITED1 to p300/CBP and Smad-mediated transcription CC transactivation (By similarity). Component of the PRP19-CDC5L splicing CC complex composed of a core complex comprising a homotetramer of PRPF19, CC CDC5L, PLRG1 and BCAS2, and at least three less stably associated CC proteins CTNNBL1, CWC15 and HSPA8 (By similarity). Interacts with TRIM5 CC (By similarity). Part of a complex composed at least of ASH2L, EMSY, CC HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this CC complex may have a histone H3-specific methyltransferase activity (By CC similarity). Interacts with METTL21A (By similarity). Following LPS CC binding, may form a complex with CXCR4, GDF5 and HSP90AA1 (By CC similarity). Interacts with PRKN (By similarity). Interacts with FOXP3 CC (By similarity). Interacts with DNAJC9 (via J domain) (By similarity). CC Interacts with MLLT11 (By similarity). Interacts with RNF207 (By CC similarity). Interacts with DNAJC21 (By similarity). Interacts with CC DNAJB2 (By similarity). Interacts with TTC1 (via TPR repeats) (By CC similarity). Interacts with SGTA (via TPR repeats) (PubMed:15708368). CC Interacts with HSF1 (via transactivation domain) (By similarity). CC Interacts with HOPX, STUB1, HSP40, HSP90, BAG2 and BAG3 (By CC similarity). Interacts with DNAJC12 (By similarity). Interacts with CC HSPC138 (By similarity). Interacts with ZMYND10 (By similarity). CC Interacts with VGF-derived peptide TLQP-21 (By similarity). Interacts CC with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is CC impaired in the absence of GIMAP5 (By similarity). Interacts with CC NLPR12 (By similarity). Interacts with TTC4 (By similarity). Interacts CC with TOMM70; the interaction is required for preprotein mitochondrial CC import (By similarity). May interact with DNJC9; the interaction seems CC to be histone-dependent (By similarity). Interacts with BAG5 and JPH2; CC the interaction with JPH2 is increased in the presence of BAG5 (By CC similarity). Interacts with DNAJC6 (via J domain) in an ATP-dependent CC manner; this interaction stimulates the HSPA8's ATPase activity. Forms CC a complex composed of HSPA8, CLTC and DNAJC6 (By similarity). Interacts CC with HSPA8; this interaction modulates migratory and antigen-presenting CC capacities of dendritic cells (By similarity). CC {ECO:0000250|UniProtKB:P11142, ECO:0000250|UniProtKB:P19120, CC ECO:0000250|UniProtKB:P63017, ECO:0000269|PubMed:10567422, CC ECO:0000269|PubMed:15708368}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11142}. CC Melanosome {ECO:0000250|UniProtKB:P11142}. Nucleus, nucleolus CC {ECO:0000250|UniProtKB:P11142}. Cell membrane CC {ECO:0000250|UniProtKB:P11142}. Lysosome membrane CC {ECO:0000250|UniProtKB:P11142}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P11142}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P11142}. Note=Localized in cytoplasmic mRNP CC granules containing untranslated mRNAs. Translocates rapidly from the CC cytoplasm to the nuclei, and especially to the nucleoli, upon heat CC shock. {ECO:0000250|UniProtKB:P11142}. CC -!- INDUCTION: Constitutively synthesized. CC -!- DOMAIN: The N-terminal nucleotide binding domain (NBD) (also known as CC the ATPase domain) is responsible for binding and hydrolyzing ATP. The CC C-terminal substrate-binding domain (SBD) (also known as peptide- CC binding domain) binds to the client/substrate proteins. The two domains CC are allosterically coupled so that, when ATP is bound to the NBD, the CC SBD binds relatively weakly to clients. When ADP is bound in the NBD, a CC conformational change enhances the affinity of the SBD for client CC proteins. {ECO:0000250|UniProtKB:P11142}. CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:P11142}. CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P11142}. CC -!- PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding. CC {ECO:0000250|UniProtKB:P11142}. CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00054; CAA68265.1; -; Genomic_DNA. DR EMBL; M11942; AAA41354.1; -; mRNA. DR EMBL; BC061547; AAH61547.1; -; mRNA. DR EMBL; BC098914; AAH98914.1; -; mRNA. DR PIR; S07197; S07197. DR RefSeq; NP_077327.1; NM_024351.2. DR PDB; 1CKR; NMR; -; A=385-543. DR PDB; 1UD0; X-ray; 3.45 A; A/B/C/D=542-646. DR PDB; 2V7Z; X-ray; 3.50 A; A/B=1-543. DR PDB; 7HSC; NMR; -; A=385-543. DR AlphaFoldDB; P63018; -. DR MDposit; P63018; -. DR SMR; P63018; -. DR BioGRID; 246629; 27. DR CORUM; P63018; -. DR DIP; DIP-33262N; -. DR FunCoup; P63018; 3304. DR IntAct; P63018; 16. DR MINT; P63018; -. DR STRING; 10116.ENSRNOP00000058593; -. DR GlyGen; P63018; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P63018; -. DR PhosphoSitePlus; P63018; -. DR SwissPalm; P63018; -. DR jPOST; P63018; -. DR PaxDb; 10116-ENSRNOP00000058593; -. DR Ensembl; ENSRNOT00000044608.7; ENSRNOP00000042159.6; ENSRNOG00000034066.7. DR Ensembl; ENSRNOT00055032010; ENSRNOP00055025891; ENSRNOG00055018769. DR Ensembl; ENSRNOT00060027805; ENSRNOP00060022339; ENSRNOG00060016236. DR Ensembl; ENSRNOT00060042781; ENSRNOP00060035439; ENSRNOG00060024746. DR Ensembl; ENSRNOT00065047766; ENSRNOP00065039178; ENSRNOG00065027723. DR GeneID; 24468; -. DR KEGG; rno:24468; -. DR UCSC; RGD:621725; rat. DR AGR; RGD:621725; -. DR CTD; 3312; -. DR RGD; 621725; Hspa8. DR eggNOG; KOG0101; Eukaryota. DR GeneTree; ENSGT00950000183206; -. DR InParanoid; P63018; -. DR OMA; AYTKNQD; -. DR OrthoDB; 2401965at2759; -. DR PhylomeDB; P63018; -. DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-RNO-3371568; Attenuation phase. DR Reactome; R-RNO-3371571; HSF1-dependent transactivation. DR Reactome; R-RNO-432720; Lysosome Vesicle Biogenesis. DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis. DR Reactome; R-RNO-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR Reactome; R-RNO-72163; mRNA Splicing - Major Pathway. DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis. DR Reactome; R-RNO-8876725; Protein methylation. DR Reactome; R-RNO-888590; GABA synthesis, release, reuptake and degradation. DR Reactome; R-RNO-9833482; PKR-mediated signaling. DR EvolutionaryTrace; P63018; -. DR PRO; PR:P63018; -. DR Proteomes; UP000002494; Chromosome 8. DR ExpressionAtlas; P63018; baseline and differential. DR GO; GO:0032279; C:asymmetric synapse; IDA:RGD. DR GO; GO:0005776; C:autophagosome; IDA:RGD. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:ParkinsonsUK-UCL. DR GO; GO:0043198; C:dendritic shaft; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0070062; C:extracellular exosome; ISO:RGD. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0098690; C:glycinergic synapse; IDA:SynGO. DR GO; GO:0005882; C:intermediate filament; IDA:RGD. DR GO; GO:0005770; C:late endosome; ISO:RGD. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:1990836; C:lysosomal matrix; IDA:MGI. DR GO; GO:0005765; C:lysosomal membrane; IDA:MGI. DR GO; GO:0042470; C:melanosome; ISS:UniProtKB. DR GO; GO:0005874; C:microtubule; IDA:RGD. DR GO; GO:0044309; C:neuron spine; IDA:ParkinsonsUK-UCL. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0043204; C:perikaryon; IDA:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0001917; C:photoreceptor inner segment; IDA:RGD. DR GO; GO:0098684; C:photoreceptor ribbon synapse; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; IDA:ParkinsonsUK-UCL. DR GO; GO:0099634; C:postsynaptic specialization membrane; ISO:RGD. DR GO; GO:0098793; C:presynapse; IDA:SynGO. DR GO; GO:0101031; C:protein folding chaperone complex; ISO:RGD. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0000974; C:Prp19 complex; ISS:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD. DR GO; GO:0043195; C:terminal bouton; IDA:RGD. DR GO; GO:0031686; F:A1 adenosine receptor binding; IPI:RGD. DR GO; GO:0035651; F:AP-3 adaptor complex binding; ISO:RGD. DR GO; GO:0005524; F:ATP binding; ISO:RGD. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:MGI. DR GO; GO:0140545; F:ATP-dependent protein disaggregase activity; ISO:RGD. DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; ISO:RGD. DR GO; GO:1990833; F:clathrin-uncoating ATPase activity; IDA:RGD. DR GO; GO:0019899; F:enzyme binding; IPI:RGD. DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:RGD. DR GO; GO:0031072; F:heat shock protein binding; ISO:RGD. DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl. DR GO; GO:0042277; F:peptide binding; IDA:RGD. DR GO; GO:0001786; F:phosphatidylserine binding; ISO:RGD. DR GO; GO:1904593; F:prostaglandin binding; IPI:RGD. DR GO; GO:0044183; F:protein folding chaperone; IDA:RGD. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:RGD. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; ISO:RGD. DR GO; GO:0003723; F:RNA binding; IDA:RGD. DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD. DR GO; GO:0046034; P:ATP metabolic process; ISO:RGD. DR GO; GO:0008088; P:axo-dendritic transport; IEP:RGD. DR GO; GO:0071276; P:cellular response to cadmium ion; IEP:RGD. DR GO; GO:0034605; P:cellular response to heat; IEP:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD. DR GO; GO:0021549; P:cerebellum development; IEP:RGD. DR GO; GO:0061684; P:chaperone-mediated autophagy; IDA:ParkinsonsUK-UCL. DR GO; GO:1904764; P:chaperone-mediated autophagy translocation complex disassembly; IDA:ParkinsonsUK-UCL. DR GO; GO:0072318; P:clathrin coat disassembly; IDA:UniProtKB. DR GO; GO:0044849; P:estrous cycle; IEP:RGD. DR GO; GO:0030900; P:forebrain development; IEP:RGD. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEP:RGD. DR GO; GO:0044829; P:host-mediated activation of viral genome replication; ISO:RGD. DR GO; GO:0044788; P:host-mediated perturbation of viral process; ISO:RGD. DR GO; GO:0001822; P:kidney development; IEP:RGD. DR GO; GO:0061738; P:late endosomal microautophagy; ISO:RGD. DR GO; GO:0098880; P:maintenance of postsynaptic specialization structure; IDA:SynGO. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; ISO:RGD. DR GO; GO:1902904; P:negative regulation of supramolecular fiber organization; ISO:RGD. DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:RGD. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. DR GO; GO:0160020; P:positive regulation of ferroptosis; ISO:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD. DR GO; GO:0097214; P:positive regulation of lysosomal membrane permeability; IMP:RGD. DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; ISO:RGD. DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:RGD. DR GO; GO:1904592; P:positive regulation of protein refolding; IDA:RGD. DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:RGD. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IMP:RGD. DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD. DR GO; GO:0006457; P:protein folding; ISO:RGD. DR GO; GO:0006606; P:protein import into nucleus; IMP:RGD. DR GO; GO:0042026; P:protein refolding; ISS:ParkinsonsUK-UCL. DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; ISS:UniProtKB. DR GO; GO:0044743; P:protein transmembrane import into intracellular organelle; IEP:RGD. DR GO; GO:0032984; P:protein-containing complex disassembly; IMP:MGI. DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD. DR GO; GO:0099175; P:regulation of postsynapse organization; ISO:RGD. DR GO; GO:0061635; P:regulation of protein complex stability; IDA:ParkinsonsUK-UCL. DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IEP:RGD. DR GO; GO:0010045; P:response to nickel cation; IEP:RGD. DR GO; GO:1990834; P:response to odorant; IEP:RGD. DR GO; GO:0032570; P:response to progesterone; IEP:RGD. DR GO; GO:0042594; P:response to starvation; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007519; P:skeletal muscle tissue development; IEP:RGD. DR GO; GO:1990832; P:slow axonal transport; IEP:RGD. DR CDD; cd10233; ASKHA_NBD_HSP70_HSPA1; 1. DR DisProt; DP02986; -. DR FunFam; 2.60.34.10:FF:000002; Heat shock 70 kDa; 1. DR FunFam; 3.30.420.40:FF:000172; Heat shock 70 kDa protein; 1. DR FunFam; 3.30.420.40:FF:000028; heat shock 70 kDa protein-like; 1. DR FunFam; 3.30.420.40:FF:000135; Heat shock cognate 71 kDa protein; 1. DR FunFam; 3.90.640.10:FF:000134; Heat shock cognate 71 kDa protein; 1. DR FunFam; 1.20.1270.10:FF:000003; heat shock cognate 71 kDa protein-like; 1. DR FunFam; 3.30.420.40:FF:000026; Heat shock protein 70; 1. DR FunFam; 3.30.30.30:FF:000025; Uncharacterized protein; 1. DR Gene3D; 1.20.1270.10; -; 1. DR Gene3D; 3.30.30.30; -; 1. DR Gene3D; 3.30.420.40; -; 2. DR Gene3D; 3.90.640.10; Actin, Chain A, domain 4; 1. DR Gene3D; 2.60.34.10; Substrate Binding Domain Of DNAk, Chain A, domain 1; 1. DR IDEAL; IID50176; -. DR InterPro; IPR043129; ATPase_NBD. DR InterPro; IPR018181; Heat_shock_70_CS. DR InterPro; IPR029048; HSP70_C_sf. DR InterPro; IPR029047; HSP70_peptide-bd_sf. DR InterPro; IPR013126; Hsp_70_fam. DR NCBIfam; NF001413; PRK00290.1; 1. DR PANTHER; PTHR19375; HEAT SHOCK PROTEIN 70KDA; 1. DR Pfam; PF00012; HSP70; 1. DR PRINTS; PR00301; HEATSHOCK70. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR SUPFAM; SSF100934; Heat shock protein 70kD (HSP70), C-terminal subdomain; 1. DR SUPFAM; SSF100920; Heat shock protein 70kD (HSP70), peptide-binding domain; 1. DR PROSITE; PS00297; HSP70_1; 1. DR PROSITE; PS00329; HSP70_2; 1. DR PROSITE; PS01036; HSP70_3; 1. DR PDBsum; 1CKR; -. DR PDBsum; 1UD0; -. DR PDBsum; 2V7Z; -. DR PDBsum; 7HSC; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Autophagy; Cell membrane; KW Chaperone; Cytoplasm; Direct protein sequencing; Hydrolase; KW Isopeptide bond; Lysosome; Membrane; Methylation; mRNA processing; KW mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repressor; Spliceosome; Stress response; Transcription; KW Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P11142" FT CHAIN 2..646 FT /note="Heat shock cognate 71 kDa protein" FT /id="PRO_0000078273" FT REGION 2..386 FT /note="Nucleotide-binding domain (NBD)" FT /evidence="ECO:0000250|UniProtKB:P11142" FT REGION 186..377 FT /note="Interaction with BAG1" FT /evidence="ECO:0000250" FT REGION 394..509 FT /note="Substrate-binding domain (SBD)" FT /evidence="ECO:0000250|UniProtKB:P11142" FT REGION 614..646 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 616..632 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 12..15 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 14 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 15 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 71 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 202..204 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 202 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 268..275 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 268 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 271 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 275 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT BINDING 339..342 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 339 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P19120" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 108 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 246 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 319 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 319 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 328 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 329 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 469 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 512 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 512 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 524 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 541 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 561 FT /note="N6,N6,N6-trimethyllysine; by METTL21A; alternate" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 561 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 589 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 597 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT MOD_RES 601 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P11142" FT CROSSLNK 512 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:P11142" FT CROSSLNK 512 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P11142" FT STRAND 6..10 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 13..22 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 25..28 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 41..44 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 49..52 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 53..58 FT /evidence="ECO:0007829|PDB:2V7Z" FT TURN 59..61 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:2V7Z" FT TURN 71..75 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 81..86 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 91..97 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 116..135 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 152..165 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 168..174 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 175..182 FT /evidence="ECO:0007829|PDB:2V7Z" FT TURN 183..186 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 193..200 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 205..213 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 216..223 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 230..249 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 257..276 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 278..288 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 291..298 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 299..305 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 307..312 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 314..323 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 332..338 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 344..353 FT /evidence="ECO:0007829|PDB:2V7Z" FT TURN 354..356 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 357..359 FT /evidence="ECO:0007829|PDB:2V7Z" FT TURN 365..367 FT /evidence="ECO:0007829|PDB:2V7Z" FT HELIX 368..380 FT /evidence="ECO:0007829|PDB:2V7Z" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 396..399 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 401..405 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 406..408 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 409..411 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 418..429 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 431..434 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 438..445 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 447..450 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 452..461 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:7HSC" FT STRAND 472..481 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 482..484 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 485..492 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 493..496 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 497..503 FT /evidence="ECO:0007829|PDB:1CKR" FT HELIX 511..518 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 519..521 FT /evidence="ECO:0007829|PDB:1CKR" FT HELIX 522..527 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 528..530 FT /evidence="ECO:0007829|PDB:1CKR" FT TURN 532..534 FT /evidence="ECO:0007829|PDB:1CKR" FT STRAND 537..541 FT /evidence="ECO:0007829|PDB:1CKR" FT HELIX 542..553 FT /evidence="ECO:0007829|PDB:1UD0" FT HELIX 556..558 FT /evidence="ECO:0007829|PDB:1UD0" FT TURN 559..561 FT /evidence="ECO:0007829|PDB:1UD0" FT HELIX 564..595 FT /evidence="ECO:0007829|PDB:1UD0" FT HELIX 597..610 FT /evidence="ECO:0007829|PDB:1UD0" SQ SEQUENCE 646 AA; 70871 MW; 03A27B30E6C076ED CRC64; MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR PKVQVEYKGE TKSFYPEEVS SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF NDSQRQATKD AGTIAGLNVL RIINEPTAAA IAYGLDKKVG AERNVLIFDL GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH FIAEFKRKHK KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL QDFFNGKELN KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS LGIETAGGVM TVLIKRNTTI PTKQTQTFTT YSDNQPGVLI QVYEGERAMT KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI DANGILNVSA VDKSTGKENK ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN SLESYAFNMK ATVEDEKLQG KINDEDKQKI LDKCNEIISW LDKNQTAEKE EFEHQQKELE KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD //