ID HSP7C_HUMAN Reviewed; 646 AA. AC P11142; Q9H3R6; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 261. DE RecName: Full=Heat shock cognate 71 kDa protein {ECO:0000305}; DE EC=3.6.4.10 {ECO:0000269|PubMed:12526792}; DE AltName: Full=Heat shock 70 kDa protein 8; DE AltName: Full=Lipopolysaccharide-associated protein 1; DE Short=LAP-1; DE Short=LPS-associated protein 1; GN Name=HSPA8 {ECO:0000312|HGNC:HGNC:5241}; GN Synonyms=HSC70 {ECO:0000303|Ref.3}, HSP73, HSPA10; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=3037489; DOI=10.1093/nar/15.13.5181; RA Dworniczak B.P., Mirault M.-E.; RT "Structure and expression of a human gene coding for a 71 kd heat shock RT 'cognate' protein."; RL Nucleic Acids Res. 15:5181-5197(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11093761; DOI=10.1124/mol.58.6.1257; RA Tsukahara F., Yoshioka T., Muraki T.; RT "Molecular and functional characterization of HSC54, a novel variant of RT human heat shock cognate protein 70."; RL Mol. Pharmacol. 58:1257-1263(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Niswonger M.L., Berk L.R., Srivastava P.K.; RT "Complete coding sequence of human HSC70."; RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Skin; 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 [5] RP PROTEIN SEQUENCE OF 2-49; 57-71; 77-102; 103-155; 160-188; 221-247; RP 273-311; 326-342; 349-416; 424-447; 452-493; 510-517; 540-550; 570-597 AND RP 602-646, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [6] RP PROTEIN SEQUENCE OF 2-49; 57-72; 78-88; 113-188; 221-247; 300-319; 326-342; RP 349-357; 362-384; 424-447; 452-469; 510-517; 540-550 AND 584-609, CLEAVAGE RP OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma, and Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W., RA Bilsland A.E., Keith W.N.; RL Submitted (JAN-2010) to UniProtKB. RN [7] RP PROTEIN SEQUENCE OF 4-49; 57-71; 77-88; 113-126; 129-155; 160-187; 221-246; RP 300-311; 329-342; 362-384; 424-447; 540-550 AND 574-583, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [8] RP PROTEIN SEQUENCE OF 50-55; 103-107 AND 580-596. RX PubMed=1286667; DOI=10.1002/elps.11501301199; RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., RA Vandekerckhove J.; RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein RT database of normal human epidermal keratinocytes."; RL Electrophoresis 13:960-969(1992). RN [9] RP PROTEIN SEQUENCE OF 77-86; 221-236 AND 302-311. RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082; RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.; RT "Identification of the 70kD heat shock cognate protein (Hsc70) and alpha- RT actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes."; RL Biochem. Biophys. Res. Commun. 224:666-674(1996). RN [10] RP PROTEIN SEQUENCE OF 551-567, METHYLATION AT LYS-561, MUTAGENESIS OF RP LYS-561, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210; RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.; RT "A newly uncovered group of distantly related lysine methyltransferases RT preferentially interact with molecular chaperones to regulate their RT activity."; RL PLoS Genet. 9:E1003210-E1003210(2013). RN [11] RP FUNCTION. RX PubMed=2799391; DOI=10.1126/science.2799391; RA Chiang H.L., Terlecky S.R., Plant C.P., Dice J.F.; RT "A role for a 70-kilodalton heat shock protein in lysosomal degradation of RT intracellular proteins."; RL Science 246:382-385(1989). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=1586970; DOI=10.1247/csf.17.77; RA Hattori H., Liu Y.-C., Tohnai I., Ueda M., Kaneda T., Kobayashi T., RA Tanabe K., Ohtsuka K.; RT "Intracellular localization and partial amino acid sequence of a stress- RT inducible 40-kDa protein in HeLa cells."; RL Cell Struct. Funct. 17:77-86(1992). RN [13] RP INTERACTION WITH BAG1, AND DOMAIN. RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887; RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C., Aime-Sempe C., RA Xie Z., Morimoto R.I., Reed J.C.; RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70."; RL EMBO J. 16:4887-4896(1997). RN [14] RP INTERACTION WITH BAG1. RX PubMed=9679980; RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M., Kochel K., RA Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T., Yamada M., RA Reed J.C.; RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 RT and its variants in normal tissues and tumor cell lines."; RL Cancer Res. 58:3116-3131(1998). RN [15] RP INTERACTION WITH HSF1. RX PubMed=9499401; DOI=10.1101/gad.12.5.654; RA Shi Y., Mosser D.D., Morimoto R.I.; RT "Molecular chaperones as HSF1-specific transcriptional repressors."; RL Genes Dev. 12:654-666(1998). RN [16] RP INTERACTION WITH SV40 VP1 (MICROBIAL INFECTION). RX PubMed=11147964; DOI=10.1379/1466-1268(2000)005<0132:hiwsvp>2.0.co;2; RA Sainis L., Angelidis C., Pagoulatos G.N., Lazaridis L.; RT "HSC70 interactions with SV40 viral proteins differ between permissive and RT nonpermissive mammalian cells."; RL Cell Stress Chaperones 5:132-138(2000). RN [17] RP FUNCTION, AND INTERACTION WITH CITED1. RX PubMed=10722728; DOI=10.1074/jbc.275.12.8825; RA Yahata T., de Caestecker M.P., Lechleider R.J., Andriole S., Roberts A.B., RA Isselbacher K.J., Shioda T.; RT "The MSG1 non-DNA-binding transactivator binds to the p300/CBP RT coactivators, enhancing their functional link to the Smad transcription RT factors."; RL J. Biol. Chem. 275:8825-8834(2000). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11559757; DOI=10.1242/jcs.114.13.2491; RA Agarraberes F.A., Dice J.F.; RT "A molecular chaperone complex at the lysosomal membrane is required for RT protein translocation."; RL J. Cell Sci. 114:2491-2499(2001). RN [19] RP FUNCTION, IDENTIFICATION AS LPS RECEPTOR, INTERACTION WITH CXCR4; GDF5 AND RP HSP90AA1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11276205; DOI=10.1038/86342; RA Triantafilou K., Triantafilou M., Dedrick R.L.; RT "A CD14-independent LPS receptor cluster."; RL Nat. Immunol. 2:338-345(2001). RN [20] RP FUNCTION, INTERACTION WITH TOMM70, AND CATALYTIC ACTIVITY. RX PubMed=12526792; DOI=10.1016/s0092-8674(02)01250-3; RA Young J.C., Hoogenraad N.J., Hartl F.U.; RT "Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the RT mitochondrial import receptor Tom70."; RL Cell 112:41-50(2003). RN [21] RP INTERACTION WITH PACRG. RX PubMed=14532270; DOI=10.1074/jbc.m309655200; RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.; RT "A product of the human gene adjacent to parkin is a component of Lewy RT bodies and suppresses Pael receptor-induced cell death."; RL J. Biol. Chem. 278:51901-51910(2003). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [23] RP INTERACTION WITH TTC1. 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 [24] RP ISGYLATION. RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132; RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.; RT "Proteomic identification of proteins conjugated to ISG15 in mouse and RT human cells."; RL Biochem. Biophys. Res. Commun. 336:496-506(2005). RN [25] RP INTERACTION WITH TSC2, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15963462; DOI=10.1016/j.bbrc.2005.05.175; RA Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., RA Luider T.M.; RT "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex."; RL Biochem. Biophys. Res. Commun. 333:818-826(2005). RN [26] RP INTERACTION WITH DNAJB2. RX PubMed=15936278; DOI=10.1016/j.cub.2005.04.058; RA Westhoff B., Chapple J.P., van der Spuy J., Hoehfeld J., Cheetham M.E.; RT "HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients RT to the proteasome."; RL Curr. Biol. 15:1058-1064(2005). RN [27] RP FUNCTION. RX PubMed=15894275; DOI=10.1016/j.immuni.2005.03.009; RA Zhou D., Li P., Lin Y., Lott J.M., Hislop A.D., Canaday D.H., RA Brutkiewicz R.R., Blum J.S.; RT "Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens."; RL Immunity 22:571-581(2005). RN [28] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [29] RP INTERACTION WITH HERC5, AND ISGYLATION. RX PubMed=16815975; DOI=10.1073/pnas.0600397103; RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.; RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I RT IFN-induced ISGylation of protein targets."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(2006). RN [30] RP INTERACTION WITH DNAJC9. RX PubMed=17182002; DOI=10.1016/j.bbrc.2006.12.013; RA Han C., Chen T., Li N., Yang M., Wan T., Cao X.; RT "HDJC9, a novel human type C DnaJ/HSP40 member interacts with and RT cochaperones HSP70 through the J domain."; RL Biochem. Biophys. Res. Commun. 353:280-285(2007). RN [31] RP INTERACTION WITH NLRP12. RX PubMed=17947705; DOI=10.4049/jimmunol.179.9.6291; RA Arthur J.C., Lich J.D., Aziz R.K., Kotb M., Ting J.P.; RT "Heat shock protein 90 associates with monarch-1 and regulates its ability RT to promote degradation of NF-kappaB-inducing kinase."; RL J. Immunol. 179:6291-6296(2007). RN [32] RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=17289661; DOI=10.1074/mcp.m600346-mcp200; RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R., RA Johnsen A.H., Christiansen J., Nielsen F.C.; RT "Molecular composition of IMP1 ribonucleoprotein granules."; RL Mol. Cell. Proteomics 6:798-811(2007). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [34] RP INTERACTION WITH TTC4. RX PubMed=18320024; DOI=10.1371/journal.pone.0001737; RA Crevel G., Bennett D., Cotterill S.; RT "The human TPR protein TTC4 is a putative Hsp90 co-chaperone which RT interacts with CDC6 and shows alterations in transformed cells."; RL PLoS ONE 3:E0001737-E0001737(2008). RN [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [36] RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; EMSY; MATR3; ZNF335; TUBB2A; RP CCAR2; ASH2L; RBBP5 AND WDR5. RX PubMed=19131338; DOI=10.1074/jbc.m805872200; RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., Samuels H.H.; RT "Identification and characterization of a novel nuclear protein complex RT involved in nuclear hormone receptor-mediated gene regulation."; RL J. Biol. Chem. 284:7542-7552(2009). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [38] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-246; LYS-319; LYS-589; LYS-597 RP AND LYS-601, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [39] RP INTERACTION WITH DNAJB12. RX PubMed=21150129; DOI=10.1247/csf.10023; RA Yamamoto Y.H., Kimura T., Momohara S., Takeuchi M., Tani T., Kimata Y., RA Kadokura H., Kohno K.; RT "A novel ER J-protein DNAJB12 accelerates ER-associated degradation of RT membrane proteins including CFTR."; RL Cell Struct. Funct. 35:107-116(2010). RN [40] RP INTERACTION WITH TRIM5. RX PubMed=20053985; DOI=10.1074/jbc.m109.040618; RA Hwang C.Y., Holl J., Rajan D., Lee Y., Kim S., Um M., Kwon K.S., Song B.; RT "Hsp70 interacts with the retroviral restriction factor TRIM5alpha and RT assists the folding of TRIM5alpha."; RL J. Biol. Chem. 285:7827-7837(2010). RN [41] RP IDENTIFICATION AS A COMPONENT OF THE PRP19-CDC5L COMPLEX, AND SUBCELLULAR RP LOCATION. RX PubMed=20176811; DOI=10.1128/mcb.01505-09; RA Grote M., Wolf E., Will C.L., Lemm I., Agafonov D.E., Schomburg A., RA Fischle W., Urlaub H., Luhrmann R.; RT "Molecular architecture of the human Prp19/CDC5L complex."; RL Mol. Cell. Biol. 30:2105-2119(2010). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [43] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [44] RP INTERACTION WITH DNAJB12. RX PubMed=21148293; DOI=10.1091/mbc.e10-09-0760; RA Grove D.E., Fan C.Y., Ren H.Y., Cyr D.M.; RT "The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70 cooperate to RT facilitate RMA1 E3-dependent degradation of nascent CFTRDeltaF508."; RL Mol. Biol. Cell 22:301-314(2011). RN [45] RP INTERACTION WITH DNAJB14. RX PubMed=23018488; DOI=10.1247/csf.12017; RA Sopha P., Kadokura H., Yamamoto Y.H., Takeuchi M., Saito M., Tsuru A., RA Kohno K.; RT "A novel mammalian ER-located J-protein, DNAJB14, can accelerate ERAD of RT misfolded membrane proteins."; RL Cell Struct. Funct. 37:177-187(2012). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [47] RP REVIEW. RX PubMed=24121476; DOI=10.4161/auto.26448; RA Stricher F., Macri C., Ruff M., Muller S.; RT "HSPA8/HSC70 chaperone protein: structure, function, and chemical RT targeting."; RL Autophagy 9:1937-1954(2013). RN [48] RP SUBUNIT, AND INTERACTION WITH STUB1. RX PubMed=23865999; DOI=10.1021/bi4009209; RA Smith M.C., Scaglione K.M., Assimon V.A., Patury S., Thompson A.D., RA Dickey C.A., Southworth D.R., Paulson H.L., Gestwicki J.E., Zuiderweg E.R.; RT "The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a RT dynamic, tethered complex."; RL Biochemistry 52:5354-5364(2013). RN [49] RP INTERACTION WITH FOXP3. RX PubMed=23973223; DOI=10.1016/j.immuni.2013.08.006; RA Chen Z., Barbi J., Bu S., Yang H.Y., Li Z., Gao Y., Jinasena D., Fu J., RA Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J., Gao Z., Tian H., RA Li Y., Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J., Dang E., Li Z., RA Wang H., Luo W., Li L., Semenza G.L., Zheng S.G., Loser K., Tsun A., RA Greene M.I., Pardoll D.M., Pan F., Li B.; RT "The ubiquitin ligase Stub1 negatively modulates regulatory T cell RT suppressive activity by promoting degradation of the transcription factor RT Foxp3."; RL Immunity 39:272-285(2013). RN [50] RP METHYLATION AT LYS-561, MUTAGENESIS OF LYS-561, AND INTERACTION WITH RP METTL21A. RX PubMed=23921388; DOI=10.1074/jbc.m113.483248; RA Jakobsson M.E., Moen A., Bousset L., Egge-Jacobsen W., Kernstock S., RA Melki R., Falnes P.O.; RT "Identification and characterization of a novel human methyltransferase RT modulating Hsp70 function through lysine methylation."; RL J. Biol. Chem. 288:27752-27763(2013). RN [51] RP FUNCTION IN ERAD, AND INTERACTION WITH STUB1. RX PubMed=23990462; DOI=10.1074/jbc.m113.479345; RA Matsumura Y., Sakai J., Skach W.R.; RT "Endoplasmic reticulum protein quality control is determined by cooperative RT interactions between Hsp/c70 protein and the CHIP E3 ligase."; RL J. Biol. Chem. 288:31069-31079(2013). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329 AND SER-541, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [53] RP INTERACTION WITH PRKN. RX PubMed=24270810; DOI=10.1038/nature12748; RA Hasson S.A., Kane L.A., Yamano K., Huang C.H., Sliter D.A., Buehler E., RA Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E., Youle R.J.; RT "High-content genome-wide RNAi screens identify regulators of parkin RT upstream of mitophagy."; RL Nature 504:291-295(2013). RN [54] RP INTERACTION WITH DNAJC12. RX PubMed=24122553; DOI=10.1007/s12192-013-0471-6; RA Choi J., Djebbar S., Fournier A., Labrie C.; RT "The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic RT reticulum stress."; RL Cell Stress Chaperones 19:439-446(2014). RN [55] RP INTERACTION WITH MLLT11. RX PubMed=24880125; DOI=10.1016/j.yexcr.2014.05.013; RA Li P., Ji M., Lu F., Zhang J., Li H., Cui T., Li Wang X., Tang D., Ji C.; RT "Degradation of AF1Q by chaperone-mediated autophagy."; RL Exp. Cell Res. 327:48-56(2014). RN [56] RP FUNCTION, AND INTERACTION WITH BAG1; BAG2; BAG3 AND HSPH1. RX PubMed=24318877; DOI=10.1074/jbc.m113.521997; RA Rauch J.N., Gestwicki J.E.; RT "Binding of human nucleotide exchange factors to heat shock protein 70 RT (Hsp70) generates functionally distinct complexes in vitro."; RL J. Biol. Chem. 289:1402-1414(2014). RN [57] RP INTERACTION WITH RNF207. RX PubMed=25281747; DOI=10.1074/jbc.m114.592295; RA Roder K., Werdich A.A., Li W., Liu M., Kim T.Y., Organ-Darling L.E., RA Moshal K.S., Hwang J.M., Lu Y., Choi B.R., MacRae C.A., Koren G.; RT "RING finger protein RNF207, a novel regulator of cardiac excitation."; RL J. Biol. Chem. 289:33730-33740(2014). RN [58] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [59] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-469 AND LYS-561, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [60] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-512, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [61] RP INTERACTION WITH DNAJB12 AND DNAJB14. RX PubMed=24732912; DOI=10.1371/journal.pone.0094322; RA Goodwin E.C., Motamedi N., Lipovsky A., Fernandez-Busnadiego R., DiMaio D.; RT "Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus RT by membranes associated with a novel nuclear pore structure."; RL PLoS ONE 9:E94322-E94322(2014). RN [62] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-512, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [63] RP INTERACTION WITH HSPA8. RX PubMed=25760597; DOI=10.1107/s1399004714026881; RA Song J., Kose S., Watanabe A., Son S.Y., Choi S., Hong H., Yamashita E., RA Park I.Y., Imamoto N., Lee S.J.; RT "Structural and functional analysis of Hikeshi, a new nuclear transport RT receptor of Hsp70s."; RL Acta Crystallogr. D 71:473-483(2015). RN [64] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [65] RP INTERACTION WITH DNAJC21. RX PubMed=27346687; DOI=10.1016/j.ajhg.2016.05.002; RA Tummala H., Walne A.J., Williams M., Bockett N., Collopy L., Cardoso S., RA Ellison A., Wynn R., Leblanc T., Fitzgibbon J., Kelsell D.P., RA van Heel D.A., Payne E., Plagnol V., Dokal I., Vulliamy T.; RT "DNAJC21 mutations link a cancer-prone bone marrow failure syndrome to RT corruption in 60S ribosome subunit maturation."; RL Am. J. Hum. Genet. 99:115-124(2016). RN [66] RP REVIEW. RX PubMed=26865365; DOI=10.1007/s12192-016-0676-6; RA Radons J.; RT "The human HSP70 family of chaperones: where do we stand?"; RL Cell Stress Chaperones 21:379-404(2016). RN [67] RP INTERACTION WITH CDKN1B AND HTN3. RX PubMed=26775844; DOI=10.1016/j.bbrc.2016.01.072; RA Imamura Y., Wang P.L., Masuno K., Sogawa N.; RT "Salivary protein histatin 3 regulates cell proliferation by enhancing RT p27(Kip1) and heat shock cognate protein 70 ubiquitination."; RL Biochem. Biophys. Res. Commun. 470:269-274(2016). RN [68] RP FUNCTION, INTERACTION WITH BAG1 AND BAG3, REGION NBD, AND REGION SBD. RX PubMed=27474739; DOI=10.1074/jbc.m116.742502; RA Rauch J.N., Zuiderweg E.R., Gestwicki J.E.; RT "Non-canonical interactions between heat shock cognate protein 70 (Hsc70) RT and Bcl2-associated anthanogene (BAG) co-chaperones are important for RT client release."; RL J. Biol. Chem. 291:19848-19857(2016). RN [69] RP INTERACTION WITH HOPX; STUB1; HSP40 AND HSP90. RX PubMed=27708256; DOI=10.1038/ncomms12882; RA Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K., RA Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H., RA Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.; RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding RT and degradation."; RL Nat. Commun. 7:12882-12882(2016). RN [70] RP INTERACTION WITH VGF. RX PubMed=28934328; DOI=10.1371/journal.pone.0185176; RA Akhter S., Chakraborty S., Moutinho D., Alvarez-Coiradas E., Rosa I., RA Vinuela J., Dominguez E., Garcia A., Requena J.R.; RT "The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa RT protein 8 (HSPA8)on the surface of SH-SY5Y cells."; RL PLoS ONE 12:E0185176-E0185176(2017). RN [71] RP INTERACTION WITH DNAJB12 AND DNAJB14. RX PubMed=27916661; DOI=10.1016/j.molcel.2016.10.027; RA Li K., Jiang Q., Bai X., Yang Y.F., Ruan M.Y., Cai S.Q.; RT "Tetrameric assembly of K(+) channels requires ER-located chaperone RT proteins."; RL Mol. Cell 65:52-65(2017). RN [72] RP INTERACTION WITH ZMYND10. RX PubMed=29601588; DOI=10.1371/journal.pgen.1007316; RA Cho K.J., Noh S.H., Han S.M., Choi W.I., Kim H.Y., Yu S., Lee J.S., RA Rim J.H., Lee M.G., Hildebrandt F., Gee H.Y.; RT "ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre- RT assembly of dynein arms."; RL PLoS Genet. 14:E1007316-E1007316(2018). RN [73] RP INTERACTION WITH HHV-1 TRANSCRIPTIONAL REGULATOR ICP22 (MICROBIAL RP INFECTION). RX PubMed=31748398; DOI=10.1128/jvi.01564-19; RA Adlakha M., Livingston C.M., Bezsonova I., Weller S.K.; RT "The Herpes Simplex Virus 1 Immediate Early Protein ICP22 Is a Functional RT Mimic of a Cellular J Protein."; RL J. Virol. 94:0-0(2020). RN [74] RP INTERACTION WITH DNJC9. RX PubMed=33857403; DOI=10.1016/j.molcel.2021.03.041; RA Hammond C.M., Bao H., Hendriks I.A., Carraro M., Garcia-Nieto A., Liu Y., RA Reveron-Gomez N., Spanos C., Chen L., Rappsilber J., Nielsen M.L., RA Patel D.J., Huang H., Groth A.; RT "DNAJC9 integrates heat shock molecular chaperones into the histone RT chaperone network."; RL Mol. Cell 0:0-0(2021). RN [75] RP INTERACTION WITH BAG5 AND JPH2. RX PubMed=35044787; DOI=10.1126/scitranslmed.abf3274; RA Hakui H., Kioka H., Miyashita Y., Nishimura S., Matsuoka K., Kato H., RA Tsukamoto O., Kuramoto Y., Takuwa A., Takahashi Y., Saito S., Ohta K., RA Asanuma H., Fu H.Y., Shinomiya H., Yamada N., Ohtani T., Sawa Y., RA Kitakaze M., Takashima S., Sakata Y., Asano Y.; RT "Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated RT cardiomyopathy requiring heart transplantation."; RL Sci. Transl. Med. 14:eabf3274-eabf3274(2022). RN [76] RP FUNCTION. RX PubMed=36586411; DOI=10.1016/j.molcel.2022.12.002; RA Wang L., Cai J., Zhao X., Ma L., Zeng P., Zhou L., Liu Y., Yang S., Cai Z., RA Zhang S., Zhou L., Yang J., Liu T., Jin S., Cui J.; RT "Palmitoylation prevents sustained inflammation by limiting NLRP3 RT inflammasome activation through chaperone-mediated autophagy."; RL Mol. Cell 0:0-0(2022). RN [77] RP INTERACTION WITH MIPEP155. RX PubMed=32671205; DOI=10.1126/sciadv.aaz2059; RA Niu L., Lou F., Sun Y., Sun L., Cai X., Liu Z., Zhou H., Wang H., Wang Z., RA Bai J., Yin Q., Zhang J., Chen L., Peng D., Xu Z., Gao Y., Tang S., Fan L., RA Wang H.; RT "A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune RT inflammation via modulating antigen presentation."; RL Sci. Adv. 6:eaaz2059-eaaz2059(2020). RN [78] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-634. RX PubMed=19586912; DOI=10.1074/jbc.m109.033894; RA Kajander T., Sachs J.N., Goldman A., Regan L.; RT "Electrostatic interactions of Hsp-organizing protein tetratricopeptide RT domains with Hsp70 and Hsp90: computational analysis and protein RT engineering."; RL J. Biol. Chem. 284:25364-25374(2009). RN [79] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP AND RP ATP ANALOGS. RX PubMed=19256508; DOI=10.1021/jm801627a; RA Williamson D.S., Borgognoni J., Clay A., Daniels Z., Dokurno P., RA Drysdale M.J., Foloppe N., Francis G.L., Graham C.J., Howes R., RA Macias A.T., Murray J.B., Parsons R., Shaw T., Surgenor A.E., Terry L., RA Wang Y., Wood M., Massey A.J.; RT "Novel adenosine-derived inhibitors of 70 kDa heat shock protein, RT discovered through structure-based design."; RL J. Med. Chem. 52:1510-1513(2009). RN [80] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP RP ANALOGS. RX PubMed=21526763; DOI=10.1021/jm101625x; RA Macias A.T., Williamson D.S., Allen N., Borgognoni J., Clay A., Daniels Z., RA Dokurno P., Drysdale M.J., Francis G.L., Graham C.J., Howes R., RA Matassova N., Murray J.B., Parsons R., Shaw T., Surgenor A.E., Terry L., RA Wang Y., Wood M., Massey A.J.; RT "Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) RT ATPase: insights into isoform selectivity."; RL J. Med. Chem. 54:4034-4041(2011). 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 CC (PubMed:2799391, PubMed:21150129, PubMed:21148293, PubMed:24732912, CC PubMed:27916661, PubMed:23018488, PubMed:36586411). This is achieved CC through cycles of ATP binding, ATP hydrolysis and ADP release, mediated CC by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, CC PubMed:27916661, PubMed:23018488, PubMed:12526792). The co-chaperones CC have been shown to not only regulate different steps of the ATPase CC cycle of HSP70, but they also have an individual specificity such that CC one co-chaperone may promote folding of a substrate while another may CC promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, CC PubMed:27916661, PubMed:23018488, PubMed:12526792). The affinity of CC HSP70 for polypeptides is regulated by its nucleotide bound state. In CC the ATP-bound form, it has a low affinity for substrate proteins. CC 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 (PubMed:24318877, PubMed:27474739, PubMed:24121476, CC PubMed:26865365). Plays a critical role in mitochondrial import, CC delivers preproteins to the mitochondrial import receptor TOMM70 CC (PubMed:12526792). Acts as a repressor of transcriptional activation. CC Inhibits the transcriptional coactivator activity of CITED1 on Smad- CC mediated transcription. Component of the PRP19-CDC5L complex that forms CC an integral part of the spliceosome and is required for activating pre- CC mRNA splicing. May have a scaffolding role in the spliceosome assembly CC as it contacts all other components of the core complex. Binds CC bacterial lipopolysaccharide (LPS) and mediates LPS-induced CC inflammatory response, including TNF secretion by monocytes CC (PubMed:10722728, PubMed:11276205). Substrate recognition component in CC chaperone-mediated autophagy (CMA), a selective protein degradation CC process that mediates degradation of proteins with a -KFERQ motif: CC HSPA8/HSC70 specifically recognizes and binds cytosolic proteins CC bearing a -KFERQ motif and promotes their recruitment to the surface of CC the lysosome where they bind to lysosomal protein LAMP2 CC (PubMed:2799391, PubMed:11559757, PubMed:36586411). KFERQ motif- CC containing proteins are eventually transported into the lysosomal lumen CC where they are degraded (PubMed:2799391, PubMed:11559757, CC PubMed:36586411). 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 CC (PubMed:15894275). Participates in the ER-associated degradation (ERAD) CC quality control pathway in conjunction with J domain-containing co- CC chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited CC to clathrin-coated vesicles through its interaction with DNAJC6 leading CC to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of CC clathrin-coated vesicles (By similarity). CC {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, CC ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, CC ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, CC ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, CC ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, CC ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, CC ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, CC ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, CC ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. 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:0000269|PubMed:12526792}; CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex CC containing untranslated mRNAs. Interacts with PACRG. Interacts with CC HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7. CC Interacts with DNAJB12 (via J domain) (PubMed:21150129, CC PubMed:21148293, PubMed:24732912, PubMed:27916661). Interacts with CC DNAJB14 (via J domain) (PubMed:23018488, PubMed:24732912, CC PubMed:27916661). Interacts (via C-terminus) with the E3 ligase CHIP CC forming a 210 kDa complex of one CHIP and two HSPA8 molecules. CC Interacts with CITED1 (via N-terminus); the interaction suppresses the CC association of CITED1 to p300/CBP and Smad-mediated transcription CC transactivation. Component of the PRP19-CDC5L splicing complex composed CC of 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. Interacts with TRIM5. Part of a complex composed at CC least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, CC WDR5 and ZNF335; this complex may have a histone H3-specific CC methyltransferase activity. Interacts with METTL21A. Following LPS CC binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts CC with PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain) CC (PubMed:17182002). Interacts with MLLT11 (PubMed:24880125). Interacts CC with RNF207 (PubMed:25281747). Interacts with DNAJC21 CC (PubMed:27346687). Interacts with DNAJB2 (PubMed:15936278). Interacts CC with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with SGTA (via CC TPR repeats) (By similarity). Interacts with HSF1 (via transactivation CC domain) (PubMed:9499401). Interacts with HOPX, HSP40 and HSP90 CC (PubMed:27708256). Interacts with STUB1 (PubMed:27708256). Interacts CC with BAG2 (PubMed:24318877). Interacts with BAG3 (PubMed:27474739, CC PubMed:24318877). Interacts with DNAJC12 (PubMed:24122553). Interacts CC with ZMYND10 (PubMed:29601588). Interacts with HSPC138 CC (PubMed:25760597). Interacts with BCL2L1, GIMAP5 and MCL1; the CC interaction with BCL2L1 or MCL1 is impaired in the absence of GIMAP5 CC (By similarity). Interacts with NLPR12 (PubMed:17947705). Interacts CC with TTC4 (PubMed:18320024). Interacts with TOMM70; the interaction is CC required for preprotein mitochondrial import (PubMed:12526792). May CC interact with DNJC9; the interaction seems to be histone-dependent CC (PubMed:33857403). Interacts with BAG5 and JPH2; the interaction with CC JPH2 is increased in the presence of BAG5 (PubMed:35044787). Interacts CC with VGF-derived peptide TLQP-21 (PubMed:28934328). Interacts with CC molecular chaperone MIPEP155 (via N-terminal ATP-binding region); the CC interaction results in reduced ATPase activity of HSPA8, impaired CC interaction of HSPA8 with HSP90 and reduced lysosomal antigen CC trafficking (PubMed:32671205). Interacts with CDKN1B; the interaction CC may be associated with susceptibility to ubiquitination CC (PubMed:26775844). Interacts with HTN3 peptide Hst3; the interaction CC enhances HSPA8-CDKN1B complex formation (PubMed:26775844). Interacts CC with DNAJC6 (via J domain) in an ATP-dependent manner; this interaction CC stimulates the HSPA8's ATPase activity. Forms a complex composed of CC HSPA8, CLTC and DNAJC6 (By similarity). {ECO:0000250|UniProtKB:P19120, CC ECO:0000250|UniProtKB:P63017, ECO:0000250|UniProtKB:P63018, CC ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, CC ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:14532270, CC ECO:0000269|PubMed:15708368, ECO:0000269|PubMed:15936278, CC ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:16815975, CC ECO:0000269|PubMed:17182002, ECO:0000269|PubMed:17289661, CC ECO:0000269|PubMed:17947705, ECO:0000269|PubMed:18320024, CC ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:20053985, CC ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, CC ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23865999, CC ECO:0000269|PubMed:23921388, ECO:0000269|PubMed:23973223, CC ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24122553, CC ECO:0000269|PubMed:24270810, ECO:0000269|PubMed:24318877, CC ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:24880125, CC ECO:0000269|PubMed:25281747, ECO:0000269|PubMed:25760597, CC ECO:0000269|PubMed:26775844, ECO:0000269|PubMed:27346687, CC ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27708256, CC ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:28934328, CC ECO:0000269|PubMed:29601588, ECO:0000269|PubMed:32671205, CC ECO:0000269|PubMed:33857403, ECO:0000269|PubMed:35044787, CC ECO:0000269|PubMed:9305631, ECO:0000269|PubMed:9499401, CC ECO:0000269|PubMed:9679980}. CC -!- SUBUNIT: (Microbial infection) Interacts with SV40 VP1. CC {ECO:0000269|PubMed:11147964}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpes virus 1 CC (HHV-1) transcriptional regulator ICP22; this interaction recruits CC HSPA8/HSP40 to discrete nuclear foci. {ECO:0000269|PubMed:31748398}. CC -!- INTERACTION: CC P11142; P60709: ACTB; NbExp=2; IntAct=EBI-351896, EBI-353944; CC P11142; Q9GZX7: AICDA; NbExp=2; IntAct=EBI-351896, EBI-3834328; CC P11142; P05067: APP; NbExp=8; IntAct=EBI-351896, EBI-77613; CC P11142; P49407: ARRB1; NbExp=4; IntAct=EBI-351896, EBI-743313; CC P11142; P32121: ARRB2; NbExp=4; IntAct=EBI-351896, EBI-714559; CC P11142; Q9NQ11: ATP13A2; NbExp=2; IntAct=EBI-351896, EBI-6308763; CC P11142; P54253: ATXN1; NbExp=13; IntAct=EBI-351896, EBI-930964; CC P11142; Q99933: BAG1; NbExp=13; IntAct=EBI-351896, EBI-1030678; CC P11142; O95816: BAG2; NbExp=8; IntAct=EBI-351896, EBI-355275; CC P11142; O95429: BAG4; NbExp=6; IntAct=EBI-351896, EBI-2949658; CC P11142; P00533: EGFR; NbExp=7; IntAct=EBI-351896, EBI-297353; CC P11142; Q9BQI3: EIF2AK1; NbExp=2; IntAct=EBI-351896, EBI-640377; CC P11142; O14976: GAK; NbExp=7; IntAct=EBI-351896, EBI-714707; CC P11142; P01893: HLA-H; NbExp=2; IntAct=EBI-351896, EBI-3197925; CC P11142; P34932: HSPA4; NbExp=6; IntAct=EBI-351896, EBI-356933; CC P11142; Q9NZL4: HSPBP1; NbExp=12; IntAct=EBI-351896, EBI-356763; CC P11142; P42858: HTT; NbExp=14; IntAct=EBI-351896, EBI-466029; CC P11142; PRO_0000015820 [P01308]: INS; NbExp=2; IntAct=EBI-351896, EBI-20765227; CC P11142; P05412: JUN; NbExp=3; IntAct=EBI-351896, EBI-852823; CC P11142; P00338: LDHA; NbExp=4; IntAct=EBI-351896, EBI-372327; CC P11142; Q5S007: LRRK2; NbExp=6; IntAct=EBI-351896, EBI-5323863; CC P11142; P10636: MAPT; NbExp=5; IntAct=EBI-351896, EBI-366182; CC P11142; P10636-6: MAPT; NbExp=3; IntAct=EBI-351896, EBI-7796455; CC P11142; P40692: MLH1; NbExp=2; IntAct=EBI-351896, EBI-744248; CC P11142; P14598: NCF1; NbExp=2; IntAct=EBI-351896, EBI-395044; CC P11142; O60260-5: PRKN; NbExp=9; IntAct=EBI-351896, EBI-21251460; CC P11142; Q15428: SF3A2; NbExp=2; IntAct=EBI-351896, EBI-2462271; CC P11142; Q9UNE7: STUB1; NbExp=8; IntAct=EBI-351896, EBI-357085; CC P11142; P61764: STXBP1; NbExp=2; IntAct=EBI-351896, EBI-960169; CC P11142; Q8TDR0: TRAF3IP1; NbExp=3; IntAct=EBI-351896, EBI-928811; CC P11142; O00635: TRIM38; NbExp=6; IntAct=EBI-351896, EBI-2130415; CC P11142; Q8AZK7: EBNA-LP; Xeno; NbExp=3; IntAct=EBI-351896, EBI-1185167; CC P11142; Q5WZW9: lpl0262; Xeno; NbExp=2; IntAct=EBI-351896, EBI-40262565; CC P11142; P03485: M; Xeno; NbExp=4; IntAct=EBI-351896, EBI-2547543; CC P11142; PRO_0000045603 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-351896, EBI-6927928; CC P11142-1; Q9UNE7-1: STUB1; NbExp=4; IntAct=EBI-351908, EBI-15687717; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17289661}. CC Melanosome {ECO:0000269|PubMed:17081065}. Nucleus, nucleolus CC {ECO:0000269|PubMed:1586970}. Cell membrane. Lysosome membrane CC {ECO:0000269|PubMed:11559757}; Peripheral membrane protein CC {ECO:0000269|PubMed:11559757}; Cytoplasmic side CC {ECO:0000269|PubMed:11559757}. Note=Localized in cytoplasmic mRNP CC granules containing untranslated mRNAs (PubMed:17289661). Translocates CC rapidly from the cytoplasm to the nuclei, and especially to the CC nucleoli, upon heat shock (PubMed:1586970). CC {ECO:0000269|PubMed:1586970, ECO:0000269|PubMed:17289661}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11142-1; Sequence=Displayed; CC Name=2; Synonyms=HSC54; CC IsoId=P11142-2; Sequence=VSP_002427; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11276205}. 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:0000269|PubMed:9305631}. CC -!- PTM: Acetylated. {ECO:0000269|Ref.5, ECO:0000269|Ref.6}. CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798, CC ECO:0000269|PubMed:16815975}. CC -!- PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding. 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; Y00371; CAA68445.1; -; Genomic_DNA. DR EMBL; AB034951; BAB18615.1; -; mRNA. DR EMBL; AF352832; AAK17898.1; -; mRNA. DR EMBL; BC016179; AAH16179.1; -; mRNA. DR EMBL; BC016660; AAH16660.1; -; mRNA. DR EMBL; BC019816; AAH19816.1; -; mRNA. DR CCDS; CCDS44754.1; -. [P11142-2] DR CCDS; CCDS8440.1; -. [P11142-1] DR PIR; A27077; A27077. DR RefSeq; NP_006588.1; NM_006597.5. [P11142-1] DR RefSeq; NP_694881.1; NM_153201.3. [P11142-2] DR RefSeq; XP_011541100.1; XM_011542798.1. [P11142-1] DR PDB; 3AGY; X-ray; 1.85 A; C/D/F=639-646. DR PDB; 3AGZ; X-ray; 2.51 A; C/D/E/F=639-646. DR PDB; 3ESK; X-ray; 2.05 A; B=635-646. DR PDB; 3FZF; X-ray; 2.20 A; A=4-381. DR PDB; 3FZH; X-ray; 2.00 A; A=4-381. DR PDB; 3FZK; X-ray; 2.10 A; A=4-381. DR PDB; 3FZL; X-ray; 2.20 A; A=4-381. DR PDB; 3FZM; X-ray; 2.30 A; A=4-381. DR PDB; 3LDQ; X-ray; 1.90 A; A=4-381. DR PDB; 3M3Z; X-ray; 2.10 A; A=4-381. DR PDB; 4H5N; X-ray; 1.86 A; A/B=2-384. DR PDB; 4H5R; X-ray; 1.64 A; A/B=2-384. DR PDB; 4H5T; X-ray; 1.90 A; A=2-384. DR PDB; 4H5V; X-ray; 1.75 A; A=2-384. DR PDB; 4H5W; X-ray; 1.94 A; A/B=2-384. DR PDB; 4HWI; X-ray; 2.27 A; A=5-381. DR PDB; 4KBQ; X-ray; 2.91 A; C/D=541-646. DR PDB; 5AQF; X-ray; 1.88 A; A/C=1-381. DR PDB; 5AQG; X-ray; 2.24 A; A/C/E=1-381. DR PDB; 5AQH; X-ray; 2.00 A; A=1-381. DR PDB; 5AQI; X-ray; 1.98 A; A/C=1-381. DR PDB; 5AQJ; X-ray; 1.96 A; A/C/E=1-381. DR PDB; 5AQK; X-ray; 2.09 A; A=1-381. DR PDB; 5AQL; X-ray; 1.69 A; A/C=1-381. DR PDB; 5AQM; X-ray; 1.63 A; A/C=1-381. DR PDB; 5AQN; X-ray; 2.45 A; A/C/E=1-381. DR PDB; 5AQO; X-ray; 2.12 A; A/C/E=1-381. DR PDB; 5AQP; X-ray; 2.08 A; A/C/E=1-381. DR PDB; 5AQQ; X-ray; 2.72 A; A/C/E=1-381. DR PDB; 5AQR; X-ray; 1.91 A; A/C/E=1-381. DR PDB; 5AQS; X-ray; 2.00 A; A/C=1-381. DR PDB; 5AQT; X-ray; 1.90 A; A=1-381. DR PDB; 5AQU; X-ray; 1.92 A; A=1-381. DR PDB; 5AQV; X-ray; 1.75 A; A=1-381. DR PDB; 6B1I; X-ray; 2.30 A; A/B=5-381. DR PDB; 6B1M; X-ray; 1.90 A; A/B=5-381. DR PDB; 6B1N; X-ray; 1.80 A; A/B=5-381. DR PDB; 6ZYJ; X-ray; 1.85 A; A/B=5-384. DR PDBsum; 3AGY; -. DR PDBsum; 3AGZ; -. DR PDBsum; 3ESK; -. DR PDBsum; 3FZF; -. DR PDBsum; 3FZH; -. DR PDBsum; 3FZK; -. DR PDBsum; 3FZL; -. DR PDBsum; 3FZM; -. DR PDBsum; 3LDQ; -. DR PDBsum; 3M3Z; -. DR PDBsum; 4H5N; -. DR PDBsum; 4H5R; -. DR PDBsum; 4H5T; -. DR PDBsum; 4H5V; -. DR PDBsum; 4H5W; -. DR PDBsum; 4HWI; -. DR PDBsum; 4KBQ; -. DR PDBsum; 5AQF; -. DR PDBsum; 5AQG; -. DR PDBsum; 5AQH; -. DR PDBsum; 5AQI; -. DR PDBsum; 5AQJ; -. DR PDBsum; 5AQK; -. DR PDBsum; 5AQL; -. DR PDBsum; 5AQM; -. DR PDBsum; 5AQN; -. DR PDBsum; 5AQO; -. DR PDBsum; 5AQP; -. DR PDBsum; 5AQQ; -. DR PDBsum; 5AQR; -. DR PDBsum; 5AQS; -. DR PDBsum; 5AQT; -. DR PDBsum; 5AQU; -. DR PDBsum; 5AQV; -. DR PDBsum; 6B1I; -. DR PDBsum; 6B1M; -. DR PDBsum; 6B1N; -. DR PDBsum; 6ZYJ; -. DR AlphaFoldDB; P11142; -. DR BMRB; P11142; -. DR SASBDB; P11142; -. DR SMR; P11142; -. DR BioGRID; 109544; 2741. DR ComplexPortal; CPX-5824; PRP19-CDC5L complex. DR CORUM; P11142; -. DR DIP; DIP-32874N; -. DR IntAct; P11142; 495. DR MINT; P11142; -. DR STRING; 9606.ENSP00000437125; -. DR BindingDB; P11142; -. DR ChEMBL; CHEMBL1275223; -. DR DrugBank; DB07045; (2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol. DR DrugBank; DB11638; Artenimol. DR DrugBank; DB09130; Copper. DR DrugBank; DB01254; Dasatinib. DR DrugCentral; P11142; -. DR MoonDB; P11142; Predicted. DR GlyConnect; 1299; 1 N-Linked glycan (1 site). DR GlyCosmos; P11142; 1 site, 1 glycan. DR GlyGen; P11142; 3 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P11142; -. DR MetOSite; P11142; -. DR PhosphoSitePlus; P11142; -. DR SwissPalm; P11142; -. DR BioMuta; HSPA8; -. DR DMDM; 123648; -. DR DOSAC-COBS-2DPAGE; P11142; -. DR OGP; P11142; -. DR REPRODUCTION-2DPAGE; IPI00003865; -. DR EPD; P11142; -. DR jPOST; P11142; -. DR MassIVE; P11142; -. DR MaxQB; P11142; -. DR PaxDb; 9606-ENSP00000432083; -. DR PeptideAtlas; P11142; -. DR PRIDE; P11142; -. DR ProteomicsDB; 52698; -. [P11142-1] DR ProteomicsDB; 52699; -. [P11142-2] DR Pumba; P11142; -. DR TopDownProteomics; P11142-1; -. [P11142-1] DR TopDownProteomics; P11142-2; -. [P11142-2] DR Antibodypedia; 3675; 1343 antibodies from 44 providers. DR DNASU; 3312; -. DR Ensembl; ENST00000227378.7; ENSP00000227378.3; ENSG00000109971.14. [P11142-1] DR Ensembl; ENST00000453788.6; ENSP00000404372.2; ENSG00000109971.14. [P11142-2] DR Ensembl; ENST00000532636.5; ENSP00000437125.1; ENSG00000109971.14. [P11142-1] DR Ensembl; ENST00000534624.6; ENSP00000432083.1; ENSG00000109971.14. [P11142-1] DR GeneID; 3312; -. DR KEGG; hsa:3312; -. DR MANE-Select; ENST00000534624.6; ENSP00000432083.1; NM_006597.6; NP_006588.1. DR UCSC; uc001pyp.5; human. [P11142-1] DR AGR; HGNC:5241; -. DR CTD; 3312; -. DR DisGeNET; 3312; -. DR GeneCards; HSPA8; -. DR HGNC; HGNC:5241; HSPA8. DR HPA; ENSG00000109971; Low tissue specificity. DR MIM; 600816; gene. DR neXtProt; NX_P11142; -. DR OpenTargets; ENSG00000109971; -. DR PharmGKB; PA29507; -. DR VEuPathDB; HostDB:ENSG00000109971; -. DR eggNOG; KOG0101; Eukaryota. DR GeneTree; ENSGT00950000183206; -. DR HOGENOM; CLU_005965_3_0_1; -. DR InParanoid; P11142; -. DR OMA; KANPIMM; -. DR OrthoDB; 143at2759; -. DR PhylomeDB; P11142; -. DR TreeFam; TF105042; -. DR BRENDA; 7.4.2.3; 2681. DR PathwayCommons; P11142; -. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-3371568; Attenuation phase. DR Reactome; R-HSA-3371571; HSF1-dependent transactivation. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR Reactome; R-HSA-447041; CHL1 interactions. DR Reactome; R-HSA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8876725; Protein methylation. DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation. DR Reactome; R-HSA-9613354; Lipophagy. DR Reactome; R-HSA-9613829; Chaperone Mediated Autophagy. DR Reactome; R-HSA-9615710; Late endosomal microautophagy. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P11142; -. DR SIGNOR; P11142; -. DR BioGRID-ORCS; 3312; 458 hits in 1183 CRISPR screens. DR ChiTaRS; HSPA8; human. DR EvolutionaryTrace; P11142; -. DR GeneWiki; HSPA8; -. DR GenomeRNAi; 3312; -. DR Pharos; P11142; Tchem. DR PRO; PR:P11142; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P11142; Protein. DR Bgee; ENSG00000109971; Expressed in corpus callosum and 112 other cell types or tissues. DR ExpressionAtlas; P11142; baseline and differential. DR GO; GO:0005776; C:autophagosome; IBA:GO_Central. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0098575; C:lumenal side of lysosomal membrane; TAS:ParkinsonsUK-UCL. DR GO; GO:0043202; C:lysosomal lumen; TAS:ParkinsonsUK-UCL. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IBA:GO_Central. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA: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:0101031; C:protein folding chaperone complex; IPI:ARUK-UCL. DR GO; GO:0000974; C:Prp19 complex; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0005681; C:spliceosomal complex; IPI:ComplexPortal. DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL. DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central. DR GO; GO:0140545; F:ATP-dependent protein disaggregase activity; IDA:BHF-UCL. DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro. DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; IPI:BHF-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:1990833; F:clathrin-uncoating ATPase activity; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB. DR GO; GO:0023026; F:MHC class II protein complex binding; HDA:UniProtKB. DR GO; GO:0140597; F:protein carrier chaperone; TAS:ParkinsonsUK-UCL. DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:ARUK-UCL. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB. DR GO; GO:0046034; P:ATP metabolic process; IDA:BHF-UCL. DR GO; GO:0009267; P:cellular response to starvation; TAS:ParkinsonsUK-UCL. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; TAS:Reactome. DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central. DR GO; GO:0061684; P:chaperone-mediated autophagy; ISS:ParkinsonsUK-UCL. DR GO; GO:1904764; P:chaperone-mediated autophagy translocation complex disassembly; ISS:ParkinsonsUK-UCL. DR GO; GO:0072318; P:clathrin coat disassembly; IDA:UniProtKB. DR GO; GO:0061738; P:late endosomal microautophagy; IBA:GO_Central. DR GO; GO:0061024; P:membrane organization; TAS:Reactome. DR GO; GO:0000398; P:mRNA splicing, via spliceosome; NAS:ComplexPortal. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IDA:UniProt. DR GO; GO:1902904; P:negative regulation of supramolecular fiber organization; IDA:BHF-UCL. DR GO; GO:0006457; P:protein folding; NAS:UniProtKB. DR GO; GO:0042026; P:protein refolding; IDA:UniProtKB. DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; IDA:UniProtKB. DR GO; GO:0061635; P:regulation of protein complex stability; ISS:ParkinsonsUK-UCL. DR GO; GO:1904589; P:regulation of protein import; TAS:ParkinsonsUK-UCL. DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; TAS:ParkinsonsUK-UCL. DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB. DR GO; GO:1990832; P:slow axonal transport; IBA:GO_Central. 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 IDEAL; IID00440; -. 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. DR SWISS-2DPAGE; P11142; -. DR UCD-2DPAGE; P11142; -. DR Genevisible; P11142; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Autophagy; KW Cell membrane; Chaperone; Cytoplasm; Direct protein sequencing; KW Host-virus interaction; 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:0000269|Ref.5, ECO:0000269|Ref.6, FT ECO:0007744|PubMed:19413330" FT CHAIN 2..646 FT /note="Heat shock cognate 71 kDa protein" FT /id="PRO_0000078270" FT REGION 2..386 FT /note="Nucleotide-binding domain (NBD)" FT /evidence="ECO:0000305|PubMed:27474739" FT REGION 186..377 FT /note="Interaction with BAG1" FT REGION 394..509 FT /note="Substrate-binding domain (SBD)" FT /evidence="ECO:0000305|PubMed:27474739" FT REGION 614..646 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: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 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:0000250|UniProtKB:P19120" 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: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 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:0000269|Ref.5, ECO:0000269|Ref.6, FT ECO:0007744|PubMed:19413330" FT MOD_RES 108 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P63017" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 246 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 319 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" 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:0007744|PubMed:23186163" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 469 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" 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:0007744|PubMed:23186163" FT MOD_RES 561 FT /note="N6,N6,N6-trimethyllysine; by METTL21A; alternate" FT /evidence="ECO:0000269|PubMed:23349634, FT ECO:0000269|PubMed:23921388" FT MOD_RES 561 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 589 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 597 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 601 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 512 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 512 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447" FT VAR_SEQ 464..616 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11093761" FT /id="VSP_002427" FT VARIANT 32 FT /note="D -> Y (in dbSNP:rs11551602)" FT /id="VAR_049619" FT VARIANT 459 FT /note="F -> L (in dbSNP:rs11551598)" FT /id="VAR_049620" FT MUTAGEN 561 FT /note="K->R: Complete loss of in vitro methylation by FT METTL21A." FT /evidence="ECO:0000269|PubMed:23349634, FT ECO:0000269|PubMed:23921388" FT STRAND 7..10 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 13..22 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 25..28 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 53..57 FT /evidence="ECO:0007829|PDB:5AQM" FT TURN 58..61 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:5AQM" FT TURN 73..75 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 81..87 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 91..97 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 100..107 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 110..114 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 116..135 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 136..138 FT /evidence="ECO:0007829|PDB:5AQF" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 152..164 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 168..174 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 175..182 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 185..187 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:5AQL" FT STRAND 193..201 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 204..213 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 216..225 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 230..249 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:3LDQ" FT HELIX 257..276 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 278..288 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 291..298 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 299..305 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 307..312 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 314..324 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 333..338 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 344..353 FT /evidence="ECO:0007829|PDB:5AQM" FT TURN 354..356 FT /evidence="ECO:0007829|PDB:5AQM" FT STRAND 357..360 FT /evidence="ECO:0007829|PDB:3FZF" FT TURN 365..367 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 368..380 FT /evidence="ECO:0007829|PDB:5AQM" FT HELIX 541..556 FT /evidence="ECO:0007829|PDB:4KBQ" FT HELIX 564..582 FT /evidence="ECO:0007829|PDB:4KBQ" FT HELIX 594..612 FT /evidence="ECO:0007829|PDB:4KBQ" FT HELIX 613..616 FT /evidence="ECO:0007829|PDB:4KBQ" FT STRAND 641..644 FT /evidence="ECO:0007829|PDB:3AGY" SQ SEQUENCE 646 AA; 70898 MW; 9AA27B210730670C 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 MPGGFPGGGA PPSGGASSGP TIEEVD //