HSP7C_HUMAN
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 03-AUG-2022, entry version 252.
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|PubMed:12526792}, 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 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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; EMSY; MATR3; ZNF335; TUBB2A;
RP CCAR2; ASCL2; 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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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, activation of
CC proteolysis of misfolded proteins and the formation and dissociation of
CC protein complexes. Plays a pivotal role in the protein quality control
CC system, ensuring the correct folding of proteins, the re-folding of
CC misfolded proteins and controlling the targeting of proteins for
CC subsequent degradation (PubMed:21150129, PubMed:21148293,
CC PubMed:24732912, PubMed:27916661, PubMed:23018488). 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). Participates in the ER-associated
CC degradation (ERAD) quality control pathway in conjunction with J
CC domain-containing co-chaperones and the E3 ligase STUB1
CC (PubMed:23990462). Interacts with VGF-derived peptide TLQP-21
CC (PubMed:28934328). {ECO:0000269|PubMed:10722728,
CC ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792,
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:28934328, ECO:0000303|PubMed:24121476,
CC 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 ASCL2, 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). {ECO:0000250|UniProtKB:P63017,
CC ECO:0000250|UniProtKB:P63018, ECO:0000269|PubMed:10722728,
CC ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792,
CC ECO:0000269|PubMed:14532270, ECO:0000269|PubMed:15708368,
CC ECO:0000269|PubMed:15936278, ECO:0000269|PubMed:15963462,
CC ECO:0000269|PubMed:16815975, ECO:0000269|PubMed:17182002,
CC ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:17947705,
CC ECO:0000269|PubMed:18320024, ECO:0000269|PubMed:19131338,
CC ECO:0000269|PubMed:20053985, ECO:0000269|PubMed:21148293,
CC ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488,
CC ECO:0000269|PubMed:23865999, ECO:0000269|PubMed:23921388,
CC ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:23990462,
CC ECO:0000269|PubMed:24122553, ECO:0000269|PubMed:24270810,
CC ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912,
CC ECO:0000269|PubMed:24880125, ECO:0000269|PubMed:25281747,
CC ECO:0000269|PubMed:25760597, ECO:0000269|PubMed:27346687,
CC ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27708256,
CC ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:29601588,
CC ECO:0000269|PubMed:33857403, ECO:0000269|PubMed:9305631,
CC ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9679980}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SV40 VP1.
CC {ECO:0000269|PubMed:11147964}.
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; 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. Melanosome. Nucleus, nucleolus. Cell
CC membrane. Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Translocates rapidly from the cytoplasm to the
CC nuclei, and especially to the nucleoli, upon heat shock.
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; 1853.
DR ComplexPortal; CPX-5824; PRP19-CDC5L complex.
DR CORUM; P11142; -.
DR DIP; DIP-32874N; -.
DR IntAct; P11142; 491.
DR MINT; P11142; -.
DR STRING; 9606.ENSP00000432083; -.
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 GlyGen; P11142; 2 sites, 1 O-linked glycan (1 site).
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 SWISS-2DPAGE; P11142; -.
DR UCD-2DPAGE; P11142; -.
DR EPD; P11142; -.
DR jPOST; P11142; -.
DR MassIVE; P11142; -.
DR MaxQB; P11142; -.
DR PaxDb; P11142; -.
DR PeptideAtlas; P11142; -.
DR PRIDE; P11142; -.
DR ProteomicsDB; 52698; -. [P11142-1]
DR ProteomicsDB; 52699; -. [P11142-2]
DR TopDownProteomics; P11142-1; -. [P11142-1]
DR TopDownProteomics; P11142-2; -. [P11142-2]
DR Antibodypedia; 3675; 1192 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 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 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 SignaLink; P11142; -.
DR SIGNOR; P11142; -.
DR BioGRID-ORCS; 3312; 440 hits in 1091 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 110 other tissues.
DR ExpressionAtlas; P11142; baseline and differential.
DR Genevisible; P11142; HS.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0101031; C:chaperone complex; IPI:ARUK-UCL.
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:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098690; C:glycinergic synapse; IEA:Ensembl.
DR GO; GO:0005770; C:late endosome; IEA:Ensembl.
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; ISS:ParkinsonsUK-UCL.
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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0099524; C:postsynaptic cytosol; IBA:GO_Central.
DR GO; GO:0099634; C:postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0099523; C:presynaptic cytosol; IBA:GO_Central.
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:0051087; F:chaperone binding; IPI:ARUK-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:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0001786; F:phosphatidylserine binding; IEA:Ensembl.
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:0030674; F:protein-macromolecule adaptor activity; IPI:ARUK-UCL.
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:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
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: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; IC:ComplexPortal.
DR GO; GO:1902904; P:negative regulation of supramolecular fiber organization; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0044829; P:positive regulation by host of viral genome replication; IEA:Ensembl.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
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; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
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 GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
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; PTHR19375; 1.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
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; Alternative splicing; ATP-binding;
KW Cell membrane; Chaperone; Cytoplasm; Direct protein sequencing;
KW Host-virus interaction; Hydrolase; Isopeptide bond; Membrane; Methylation;
KW 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 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 268..275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 339..342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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
