ID HSP7C_BOVIN Reviewed; 650 AA. AC P19120; A5D968; Q3MHM4; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 29-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 208. DE RecName: Full=Heat shock cognate 71 kDa protein {ECO:0000250|UniProtKB:P11142}; DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P11142}; DE AltName: Full=Heat shock 70 kDa protein 8; GN Name=HSPA8 {ECO:0000250|UniProtKB:P11142}; GN Synonyms=HSC70 {ECO:0000303|PubMed:9585559}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain cortex; RX PubMed=2216746; DOI=10.1093/nar/18.18.5569; RA Deluca-Flaherty C., McKay D.B.; RT "Nucleotide sequence of the cDNA of a bovine 70 kilodalton heat shock RT cognate protein."; RL Nucleic Acids Res. 18:5569-5569(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Ileum; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, AND INTERACTION WITH DNAJC6. RX PubMed=8524399; DOI=10.1038/378632a0; RA Ungewickell E., Ungewickell H., Holstein S.E., Lindner R., Prasad K., RA Barouch W., Martin B., Greene L.E., Eisenberg E.; RT "Role of auxilin in uncoating clathrin-coated vesicles."; RL Nature 378:632-635(1995). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-385 IN COMPLEX WITH ADP. RX PubMed=2143562; DOI=10.1038/346623a0; RA Flaherty K.M., de Luca-Flaherty C., McKay D.B.; RT "Three-dimensional structure of the ATPase fragment of a 70K heat-shock RT cognate protein."; RL Nature 346:623-628(1990). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-385 IN COMPLEXES WITH ADP AND RP ATP. RX PubMed=8175707; DOI=10.1016/s0021-9258(18)99961-8; RA Flaherty K.M., Wilbanks S.M., Deluca-Flaherty C., McKay D.B.; RT "Structural basis of the 70-kilodalton heat shock cognate protein ATP RT hydrolytic activity. II. Structure of the active site with ADP or ATP bound RT to wild type and mutant ATPase fragment."; RL J. Biol. Chem. 269:12899-12907(1994). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-385 IN COMPLEX WITH ADP. RX PubMed=9585559; DOI=10.1021/bi973046m; RA Wilbanks S.M., McKay D.B.; RT "Structural replacement of active site monovalent cations by the epsilon- RT amino group of lysine in the ATPase fragment of bovine Hsc70."; RL Biochemistry 37:7456-7462(1998). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-381 IN COMPLEX WITH ADP. RX PubMed=9799500; DOI=10.1021/bi981510x; RA Sousa M.C., McKay D.B.; RT "The hydroxyl of threonine 13 of the bovine 70-kDa heat shock cognate RT protein is essential for transducing the ATP-induced conformational RT change."; RL Biochemistry 37:15392-15399(1998). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-381 OF MUTANTS. RX PubMed=10451379; DOI=10.1021/bi990816g; RA Johnson E.R., McKay D.B.; RT "Mapping the role of active site residues for transducing an ATP-induced RT conformational change in the bovine 70-kDa heat shock cognate protein."; RL Biochemistry 38:10823-10830(1999). RN [10] {ECO:0007744|PDB:2QW9, ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ, ECO:0007744|PDB:2QWR} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-394 IN COMPLEX WITH ADP AND RP DNAJC6, AND FUNCTION. RX PubMed=17996706; DOI=10.1016/j.molcel.2007.08.022; RA Jiang J., Maes E.G., Taylor A.B., Wang L., Hinck A.P., Lafer E.M., RA Sousa R.; RT "Structural basis of J cochaperone binding and regulation of Hsp70."; RL Mol. Cell 28:422-433(2007). RN [11] RP X-RAY CRYSTALLOGRAPHY (3.12 ANGSTROMS) OF 2-554 IN COMPLEX WITH ADP. RX PubMed=18550409; DOI=10.1016/j.molcel.2008.05.006; RA Schuermann J.P., Jiang J., Cuellar J., Llorca O., Wang L., Gimenez L.E., RA Jin S., Taylor A.B., Demeler B., Morano K.A., Hart P.J., Valpuesta J.M., RA Lafer E.M., Sousa R.; RT "Structure of the Hsp110:Hsc70 nucleotide exchange machine."; RL Mol. Cell 31:232-243(2008). 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 CC (PubMed:8524399, PubMed:17996706). {ECO:0000250|UniProtKB:P11142, CC ECO:0000269|PubMed:17996706, ECO:0000269|PubMed:8524399}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; 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: 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 (By CC similarity). Interacts with DNAJB12 (via J domain) (By similarity). CC Interacts with DNAJB14 (via J domain) (By similarity). Interacts (via CC C-terminus) with the E3 ligase STUB1 forming a 210 kDa complex of one CC STUB1 and two HSPA8 molecules (By similarity). Interacts with CITED1 CC (via N-terminus); the interaction suppresses the association of CITED1 CC to p300/CBP and Smad-mediated transcription transactivation (By CC similarity). Component of the PRP19-CDC5L splicing complex composed of CC a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and CC BCAS2, and at least three less stably associated proteins CTNNBL1, CC CWC15 and HSPA8 (By similarity). Interacts with TRIM5 (By similarity). CC Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CC CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may CC have a histone H3-specific methyltransferase activity (By similarity). CC Interacts with METTL21A (By similarity). Following LPS binding, may CC form a complex with CXCR4, GDF5 and HSP90AA1 (By similarity). Interacts CC with PRKN (By similarity). Interacts with FOXP3 (By similarity). CC Interacts with DNAJC9 (via J domain) (By similarity). Interacts with CC MLLT11 (By similarity). Interacts with RNF207 (By similarity). CC Interacts with DNAJC21 (By similarity). Interacts with DNAJB2 (By CC similarity). Interacts with TTC1 (via TPR repeats) (By similarity). CC Interacts with SGTA (via TPR repeats) (By similarity). Interacts with CC HSF1 (via transactivation domain) (By similarity). Interacts with HOPX, CC STUB1, HSP40, HSP901, BAG2 and BAG3 (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 VGF-derived peptide TLQP-21 (By CC similarity). Interacts with DNAJC6 (via J domain) in an ATP-dependent CC manner; this interaction stimulates the HSPA8's ATPase activity CC (PubMed:17996706). Forms a complex composed of HSPA8, CLTC and DNAJC6 CC (PubMed:8524399). {ECO:0000250|UniProtKB:P11142, CC ECO:0000250|UniProtKB:P63017, ECO:0000250|UniProtKB:P63018, CC ECO:0000269|PubMed:17996706, ECO:0000269|PubMed:8524399}. CC -!- INTERACTION: CC P19120; P13569: CFTR; Xeno; NbExp=2; IntAct=EBI-907802, EBI-349854; CC P19120; P26361: Cftr; Xeno; NbExp=5; IntAct=EBI-907802, EBI-6115317; 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 -!- TISSUE SPECIFICITY: Ubiquitous. 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; X53827; CAA37823.1; -; mRNA. DR EMBL; X53335; CAA37422.1; -; mRNA. DR EMBL; BT030487; ABQ12927.1; -; mRNA. DR EMBL; BC105182; AAI05183.1; -; mRNA. DR PIR; S11456; S11456. DR RefSeq; NP_776770.2; NM_174345.4. DR PDB; 1ATR; X-ray; 2.34 A; A=1-386. DR PDB; 1ATS; X-ray; 2.43 A; A=1-386. DR PDB; 1BA0; X-ray; 1.90 A; A=1-386. DR PDB; 1BA1; X-ray; 1.70 A; A=1-386. DR PDB; 1BUP; X-ray; 1.70 A; A=1-386. DR PDB; 1HPM; X-ray; 1.70 A; A=1-386. DR PDB; 1HX1; X-ray; 1.90 A; A=4-381. DR PDB; 1KAX; X-ray; 1.70 A; A=1-381. DR PDB; 1KAY; X-ray; 1.70 A; A=1-381. DR PDB; 1KAZ; X-ray; 1.70 A; A=1-381. DR PDB; 1NGA; X-ray; 2.18 A; A=1-386. DR PDB; 1NGB; X-ray; 2.18 A; A=1-386. DR PDB; 1NGC; X-ray; 2.20 A; A=1-386. DR PDB; 1NGD; X-ray; 2.18 A; A=1-386. DR PDB; 1NGE; X-ray; 2.05 A; A=1-386. DR PDB; 1NGF; X-ray; 2.17 A; A=1-386. DR PDB; 1NGG; X-ray; 2.19 A; A=1-386. DR PDB; 1NGH; X-ray; 2.23 A; A=1-386. DR PDB; 1NGI; X-ray; 2.15 A; A=1-386. DR PDB; 1NGJ; X-ray; 2.10 A; A=1-386. DR PDB; 1QQM; X-ray; 1.90 A; A=4-381. DR PDB; 1QQN; X-ray; 1.90 A; A=4-381. DR PDB; 1QQO; X-ray; 1.90 A; A=4-381. DR PDB; 1YUW; X-ray; 2.60 A; A=1-554. DR PDB; 2BUP; X-ray; 1.70 A; A=1-381. DR PDB; 2QW9; X-ray; 1.85 A; A/B=1-394. DR PDB; 2QWL; X-ray; 1.75 A; A/B=1-394. DR PDB; 2QWM; X-ray; 1.86 A; A/B=1-394. DR PDB; 2QWN; X-ray; 2.40 A; A=1-394. DR PDB; 2QWO; X-ray; 1.70 A; A=1-394. DR PDB; 2QWP; X-ray; 1.75 A; A=1-394. DR PDB; 2QWQ; X-ray; 2.21 A; A=1-394. DR PDB; 2QWR; X-ray; 2.21 A; A=1-394. DR PDB; 3C7N; X-ray; 3.12 A; B=1-554. DR PDB; 3HSC; X-ray; 1.93 A; A=1-386. DR PDB; 4FL9; X-ray; 1.90 A; A=1-554. DR PDB; 6H54; X-ray; 2.02 A; A=1-554. DR PDB; 7O6R; X-ray; 2.00 A; A=1-554. DR PDB; 7ODB; X-ray; 1.66 A; A=1-554. DR PDB; 7ODD; X-ray; 1.98 A; A=1-554. DR PDB; 7ODI; X-ray; 1.83 A; A=1-554. DR PDB; 7PLK; X-ray; 2.49 A; A=1-554. DR PDBsum; 1ATR; -. DR PDBsum; 1ATS; -. DR PDBsum; 1BA0; -. DR PDBsum; 1BA1; -. DR PDBsum; 1BUP; -. DR PDBsum; 1HPM; -. DR PDBsum; 1HX1; -. DR PDBsum; 1KAX; -. DR PDBsum; 1KAY; -. DR PDBsum; 1KAZ; -. DR PDBsum; 1NGA; -. DR PDBsum; 1NGB; -. DR PDBsum; 1NGC; -. DR PDBsum; 1NGD; -. DR PDBsum; 1NGE; -. DR PDBsum; 1NGF; -. DR PDBsum; 1NGG; -. DR PDBsum; 1NGH; -. DR PDBsum; 1NGI; -. DR PDBsum; 1NGJ; -. DR PDBsum; 1QQM; -. DR PDBsum; 1QQN; -. DR PDBsum; 1QQO; -. DR PDBsum; 1YUW; -. DR PDBsum; 2BUP; -. DR PDBsum; 2QW9; -. DR PDBsum; 2QWL; -. DR PDBsum; 2QWM; -. DR PDBsum; 2QWN; -. DR PDBsum; 2QWO; -. DR PDBsum; 2QWP; -. DR PDBsum; 2QWQ; -. DR PDBsum; 2QWR; -. DR PDBsum; 3C7N; -. DR PDBsum; 3HSC; -. DR PDBsum; 4FL9; -. DR PDBsum; 6H54; -. DR PDBsum; 7O6R; -. DR PDBsum; 7ODB; -. DR PDBsum; 7ODD; -. DR PDBsum; 7ODI; -. DR PDBsum; 7PLK; -. DR AlphaFoldDB; P19120; -. DR BMRB; P19120; -. DR EMDB; EMD-4035; -. DR EMDB; EMD-4036; -. DR SMR; P19120; -. DR BioGRID; 159144; 2. DR DIP; DIP-35481N; -. DR IntAct; P19120; 8. DR MINT; P19120; -. DR STRING; 9913.ENSBTAP00000058201; -. DR BindingDB; P19120; -. DR ChEMBL; CHEMBL1275213; -. DR PaxDb; 9913-ENSBTAP00000017497; -. DR PeptideAtlas; P19120; -. DR Ensembl; ENSBTAT00000017497.3; ENSBTAP00000017497.2; ENSBTAG00000013162.3. DR GeneID; 281831; -. DR KEGG; bta:281831; -. DR CTD; 3312; -. DR VEuPathDB; HostDB:ENSBTAG00000013162; -. DR VGNC; VGNC:54632; HSPA8. DR eggNOG; KOG0101; Eukaryota. DR GeneTree; ENSGT00950000183206; -. DR HOGENOM; CLU_005965_3_0_1; -. DR InParanoid; P19120; -. DR OrthoDB; 143at2759; -. DR TreeFam; TF105042; -. DR Reactome; R-BTA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-BTA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-BTA-3371568; Attenuation phase. DR Reactome; R-BTA-3371571; HSF1-dependent transactivation. DR Reactome; R-BTA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-72163; mRNA Splicing - Major Pathway. DR Reactome; R-BTA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-BTA-8876725; Protein methylation. DR Reactome; R-BTA-888590; GABA synthesis, release, reuptake and degradation. DR Reactome; R-BTA-9833482; PKR-mediated signaling. DR EvolutionaryTrace; P19120; -. DR PRO; PR:P19120; -. DR Proteomes; UP000009136; Chromosome 15. DR Bgee; ENSBTAG00000013162; Expressed in prefrontal cortex and 100 other cell types or tissues. DR ExpressionAtlas; P19120; baseline and differential. DR GO; GO:0005776; C:autophagosome; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB. DR GO; GO:0005764; C:lysosome; IBA:GO_Central. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0099524; C:postsynaptic cytosol; IBA:GO_Central. DR GO; GO:0099523; C:presynaptic cytosol; IBA:GO_Central. DR GO; GO:0000974; C:Prp19 complex; ISS:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB. DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW. DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central. DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro. DR GO; GO:1990833; F:clathrin-uncoating ATPase activity; IBA:GO_Central. DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central. DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB. DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central. DR GO; GO:1904764; P:chaperone-mediated autophagy translocation complex disassembly; IBA:GO_Central. DR GO; GO:0072318; P:clathrin coat disassembly; IDA:UniProtKB. DR GO; GO:0061738; P:late endosomal microautophagy; IBA:GO_Central. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0042026; P:protein refolding; IBA:GO_Central. DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; ISS:UniProtKB. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:1990832; P:slow axonal transport; IBA:GO_Central. DR GO; GO:0016191; P:synaptic vesicle uncoating; IDA:SynGO. DR CDD; cd10233; HSPA1-2_6-8-like_NBD; 1. DR Gene3D; 1.20.1270.10; -; 1. DR Gene3D; 3.30.30.30; -; 1. DR Gene3D; 3.30.420.40; -; 2. 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 PANTHER; PTHR19375:SF379; HEAT SHOCK COGNATE 71 KDA PROTEIN; 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. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Autophagy; Cell membrane; KW Chaperone; Cytoplasm; Hydrolase; Isopeptide bond; Lysosome; Membrane; KW Methylation; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repressor; Spliceosome; KW Stress response; Transcription; Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P11142" FT CHAIN 2..650 FT /note="Heat shock cognate 71 kDa protein" FT /id="PRO_0000078268" 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..650 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 12..15 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 14 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 15 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 71 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 202..204 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 202 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 268..275 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 268 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 271 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 275 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" FT BINDING 339..342 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 339 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0007744|PDB:2QWL, ECO:0007744|PDB:2QWM, FT ECO:0007744|PDB:2QWN, ECO:0007744|PDB:2QWO, FT ECO:0007744|PDB:2QWP, ECO:0007744|PDB:2QWQ" 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 CONFLICT 180 FT /note="A -> T (in Ref. 3; AAI05183)" FT /evidence="ECO:0000305" FT CONFLICT 543 FT /note="E -> K (in Ref. 1; CAA37422/CAA37823)" FT /evidence="ECO:0000305" FT STRAND 7..11 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 13..22 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 25..28 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 53..57 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 58..61 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:4FL9" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 73..75 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 81..87 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 91..97 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 100..107 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 110..114 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 116..135 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 152..164 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 168..174 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 175..182 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 185..187 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:1HX1" FT STRAND 193..201 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 204..213 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 216..225 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 230..249 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 257..276 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 277..288 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 291..298 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 299..305 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 307..312 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 314..323 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 333..338 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 344..353 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 354..356 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 365..367 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 368..380 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 386..388 FT /evidence="ECO:0007829|PDB:2QWO" FT STRAND 392..396 FT /evidence="ECO:0007829|PDB:3C7N" FT STRAND 401..405 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 406..408 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 409..414 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 419..432 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 438..449 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 450..452 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 453..461 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 474..480 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 482..484 FT /evidence="ECO:0007829|PDB:7ODD" FT STRAND 486..492 FT /evidence="ECO:0007829|PDB:7ODB" FT TURN 493..495 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 498..503 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 512..524 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 526..532 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 533..535 FT /evidence="ECO:0007829|PDB:7ODB" FT STRAND 539..542 FT /evidence="ECO:0007829|PDB:7ODB" FT HELIX 547..549 FT /evidence="ECO:0007829|PDB:7ODB" SQ SEQUENCE 650 AA; 71241 MW; FBE109C14A28B925 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 LDKCNEIINW LDKNQTAEKE EFEHQQKELE KVCNPIITKL YQSAGGMPGG MPGGMPGGFP GGGAPPSGGA SSGPTIEEVD //