ID HS71A_HUMAN Reviewed; 641 AA.
AC P0DMV8; B4E3B6; P08107; P19790; Q5JQI4; Q5SP17; Q9UQL9; Q9UQM0;
DT 27-MAY-2015, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2015, sequence version 1.
DT 10-MAY-2017, entry version 23.
DE RecName: Full=Heat shock 70 kDa protein 1A {ECO:0000312|HGNC:HGNC:5232};
DE AltName: Full=Heat shock 70 kDa protein 1;
DE Short=HSP70-1 {ECO:0000303|PubMed:14656967, ECO:0000303|PubMed:2538825};
DE Short=HSP70.1;
GN Name=HSPA1A;
GN Synonyms=HSP72 {ECO:0000303|PubMed:24318877}, HSPA1, HSX70;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM
RP 1).
RX PubMed=3931075; DOI=10.1073/pnas.82.19.6455;
RA Hunt C., Morimoto R.I.;
RT "Conserved features of eukaryotic hsp70 genes revealed by comparison
RT with the nucleotide sequence of human hsp70.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6455-6459(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM
RP 1).
RX PubMed=1700760; DOI=10.1007/BF00187095;
RA Milner C.M., Campbell R.D.;
RT "Structure and expression of the three MHC-linked HSP70 genes.";
RL Immunogenetics 32:242-251(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE
RP SPLICING (ISOFORM 1).
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASP-110, AND
RP ALTERNATIVE SPLICING (ISOFORM 1).
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S.,
RA Campbell R.D., Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1),
RP AND VARIANT ASP-110.
RG NIEHS SNPs program;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Muscle, Pancreas, PNS, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
RX PubMed=2538825; DOI=10.1073/pnas.86.6.1968;
RA Sargent C.A., Dunham I., Trowsdale J., Campbell R.D.;
RT "Human major histocompatibility complex contains genes for the major
RT heat shock protein HSP70.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1968-1972(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22 AND 617-641.
RX PubMed=3786141; DOI=10.1093/nar/14.22.8933;
RA Drabent B., Genthe A., Benecke B.-J.;
RT "In vitro transcription of a human hsp 70 heat shock gene by extracts
RT prepared from heat-shocked and non-heat-shocked human cells.";
RL Nucleic Acids Res. 14:8933-8948(1986).
RN [11]
RP PROTEIN SEQUENCE OF 4-49; 57-71; 77-155; 160-187; 221-247; 273-311;
RP 326-342; 349-357; 362-416; 424-447; 459-469; 510-517; 540-550; 574-595
RP AND 598-641, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 37-49; 57-71; 78-88; 113-126; 160-187; 221-247;
RP 302-311; 329-342; 349-357; 362-384; 540-550 AND 574-589, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
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
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [14]
RP INTERACTION WITH HSF1.
RX PubMed=7935376; DOI=10.1128/MCB.14.10.6552;
RA Rabindran S.K., Wisniewski J., Li L., Li G.C., Wu C.;
RT "Interaction between heat shock factor and hsp70 is insufficient to
RT suppress induction of DNA-binding activity in vivo.";
RL Mol. Cell. Biol. 14:6552-6560(1994).
RN [15]
RP FUNCTION, AND 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 TERT.
RX PubMed=11274138; DOI=10.1074/jbc.C100055200;
RA Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.;
RT "Stable association of hsp90 and p23, but Not hsp70, with active human
RT telomerase.";
RL J. Biol. Chem. 276:15571-15574(2001).
RN [17]
RP INTERACTION WITH DNAJC7.
RX PubMed=12853476; DOI=10.1093/emboj/cdg362;
RA Brychzy A., Rein T., Winklhofer K.F., Hartl F.U., Young J.C.,
RA Obermann W.M.;
RT "Cofactor Tpr2 combines two TPR domains and a J domain to regulate the
RT Hsp70/Hsp90 chaperone system.";
RL EMBO J. 22:3613-3623(2003).
RN [18]
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
RT complex.";
RL Biochem. Biophys. Res. Commun. 333:818-826(2005).
RN [19]
RP INTERACTION WITH PPP5C, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15383005; DOI=10.1042/BJ20040690;
RA Zeke T., Morrice N., Vazquez-Martin C., Cohen P.T.;
RT "Human protein phosphatase 5 dissociates from heat-shock proteins and
RT is proteolytically activated in response to arachidonic acid and the
RT microtubule-depolymerizing drug nocodazole.";
RL Biochem. J. 385:45-56(2005).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [21]
RP INTERACTION WITH IRAK1BP1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17233114; DOI=10.1089/dna.2006.25.704;
RA Haag Breese E., Uversky V.N., Georgiadis M.M., Harrington M.A.;
RT "The disordered amino-terminus of SIMPL interacts with members of the
RT 70-kDa heat-shock protein family.";
RL DNA Cell Biol. 25:704-714(2006).
RN [22]
RP FUNCTION AS A RECEPTOR FOR ROTAVIRUS A.
RX PubMed=16537599; DOI=10.1128/JVI.80.7.3322-3331.2006;
RA Perez-Vargas J., Romero P., Lopez S., Arias C.F.;
RT "The peptide-binding and ATPase domains of recombinant hsc70 are
RT required to interact with rotavirus and reduce its infectivity.";
RL J. Virol. 80:3322-3331(2006).
RN [23]
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 [24]
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 [25]
RP INTERACTION WITH DNAJC7.
RX PubMed=18620420; DOI=10.1021/bi800770g;
RA Moffatt N.S., Bruinsma E., Uhl C., Obermann W.M., Toft D.;
RT "Role of the cochaperone Tpr2 in Hsp90 chaperoning.";
RL Biochemistry 47:8203-8213(2008).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-108; LYS-246 AND LYS-348,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [29]
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.,
RA 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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631; SER-633 AND
RP THR-636, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
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.,
RA Buerckstuemmer T., 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 [32]
RP INTERACTION WITH CHCHD3.
RX PubMed=21081504; DOI=10.1074/jbc.M110.171975;
RA Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A.,
RA Perkins G.A., Ellisman M.H., Taylor S.S.;
RT "ChChd3, an inner mitochondrial membrane protein, is essential for
RT maintaining crista integrity and mitochondrial function.";
RL J. Biol. Chem. 286:2918-2932(2011).
RN [33]
RP FUNCTION, AND INTERACTION WITH ATF5.
RX PubMed=22528486; DOI=10.1074/jbc.M112.363622;
RA Liu X., Liu D., Qian D., Dai J., An Y., Jiang S., Stanley B., Yang J.,
RA Wang B., Liu X., Liu D.X.;
RT "Nucleophosmin (NPM1/B23) interacts with activating transcription
RT factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent
RT ATF5 degradation in hepatocellular carcinoma cells.";
RL J. Biol. Chem. 287:19599-19609(2012).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S.,
RA Fischer-Posovszky P., Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion
RT profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH
RP 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.,
RA Fu J., Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J.,
RA Gao Z., Tian H., Li Y., Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J.,
RA Dang E., Li Z., Wang H., Luo W., Li L., Semenza G.L., Zheng S.G.,
RA Loser K., Tsun A., 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
RT factor Foxp3.";
RL Immunity 39:272-285(2013).
RN [36]
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
RT methyltransferase modulating Hsp70 function through lysine
RT methylation.";
RL J. Biol. Chem. 288:27752-27763(2013).
RN [37]
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 [38]
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.,
RA Buehler E., Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E.,
RA 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 [39]
RP REVIEW.
RX PubMed=24012426; DOI=10.1016/j.tibs.2013.08.001;
RA Mayer M.P.;
RT "Hsp70 chaperone dynamics and molecular mechanism.";
RL Trends Biochem. Sci. 38:507-514(2013).
RN [40]
RP FUNCTION, AND INTERACTION WITH STUB1 AND SMAD3.
RX PubMed=24613385; DOI=10.1016/j.bbrc.2014.02.124;
RA Shang Y., Xu X., Duan X., Guo J., Wang Y., Ren F., He D., Chang Z.;
RT "Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through
RT CHIP/Stub1.";
RL Biochem. Biophys. Res. Commun. 446:387-392(2014).
RN [41]
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 [42]
RP INTERACTION WITH NOD2.
RX PubMed=24790089; DOI=10.1074/jbc.M114.557686;
RA Mohanan V., Grimes C.L.;
RT "The molecular chaperone HSP70 binds to and stabilizes NOD2, an
RT important protein involved in Crohn disease.";
RL J. Biol. Chem. 289:18987-18998(2014).
RN [43]
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
RT excitation.";
RL J. Biol. Chem. 289:33730-33740(2014).
RN [44]
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.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [45]
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.,
RA Aguiar M., Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C.,
RA Vemulapalli V., 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 [46]
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.,
RA Ayoub D., 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 [47]
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 [48]
RP FUNCTION, INTERACTION WITH NEDD1, AND SUBCELLULAR LOCATION.
RX PubMed=27137183; DOI=10.1007/s00018-016-2236-8;
RA Fang C.T., Kuo H.H., Pan T.S., Yu F.C., Yih L.H.;
RT "HSP70 regulates the function of mitotic centrosomes.";
RL Cell. Mol. Life Sci. 73:3949-3960(2016).
RN [49]
RP FUNCTION, ACETYLATION AT LYS-77, MUTAGENESIS OF LYS-77, AND
RP INTERACTION WITH NAA10; HSP40; HOPX; STUB1; HSP90 AND HDAC4.
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.,
RA Seok S.H., Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.;
RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein
RT refolding and degradation.";
RL Nat. Commun. 7:12882-12882(2016).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-382 IN COMPLEX WITH ADP,
RP AND ATP-BINDING.
RX PubMed=10216320; DOI=10.1107/S0907444999002103;
RA Osipiuk J., Walsh M.A., Freeman B.C., Morimoto R.I., Joachimiak A.;
RT "Structure of a new crystal form of human hsp70 ATPase domain.";
RL Acta Crystallogr. D 55:1105-1107(1999).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 389-641 IN COMPLEX WITH ATP
RP ANALOG, AND ATP-BINDING.
RX PubMed=20179333; DOI=10.1107/S0907444909053979;
RA Shida M., Arakawa A., Ishii R., Kishishita S., Takagi T.,
RA Kukimoto-Niino M., Sugano S., Tanaka A., Shirouzu M., Yokoyama S.;
RT "Direct inter-subdomain interactions switch between the closed and
RT open forms of the Hsp70 nucleotide-binding domain in the nucleotide-
RT free state.";
RL Acta Crystallogr. D 66:223-232(2010).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 1-387 IN COMPLEX WITH ADP,
RP AND ATP-BINDING.
RX PubMed=20072699; DOI=10.1371/journal.pone.0008625;
RA Wisniewska M., Karlberg T., Lehtio L., Johansson I., Kotenyova T.,
RA Moche M., Schuler H.;
RT "Crystal structures of the ATPase domains of four human Hsp70
RT isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and
RT HSPA5/BiP/GRP78.";
RL PLoS ONE 5:E8625-E8625(2010).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-388 IN COMPLEX WITH BAG5.
RX PubMed=20223214; DOI=10.1016/j.str.2010.01.004;
RA Arakawa A., Handa N., Ohsawa N., Shida M., Kigawa T., Hayashi F.,
RA Shirouzu M., Yokoyama S.;
RT "The C-terminal BAG domain of BAG5 induces conformational changes of
RT the Hsp70 nucleotide-binding domain for ADP-ATP exchange.";
RL Structure 18:309-319(2010).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 1-388, ATP-BINDING, AND
RP MUTAGENESIS OF ASP-10 AND ASP-199.
RX PubMed=21608060; DOI=10.1002/pro.663;
RA Arakawa A., Handa N., Shirouzu M., Yokoyama S.;
RT "Biochemical and structural studies on the high affinity of Hsp70 for
RT ADP.";
RL Protein Sci. 20:1367-1379(2011).
CC -!- FUNCTION: Molecular chaperone implicated in a wide variety of
CC cellular processes, including protection of the proteome from
CC stress, folding and transport of newly synthesized polypeptides,
CC activation of proteolysis of misfolded proteins and the formation
CC and dissociation of protein complexes. Plays a pivotal role in the
CC protein quality control system, ensuring the correct folding of
CC proteins, the re-folding of misfolded proteins and controlling the
CC targeting of proteins for subsequent degradation. This is achieved
CC through cycles of ATP binding, ATP hydrolysis and ADP release,
CC mediated by co-chaperones. The co-chaperones have been shown to
CC not only regulate different steps of the ATPase cycle, but they
CC also have an individual specificity such that one co-chaperone may
CC promote folding of a substrate while another may promote
CC degradation. The affinity for polypeptides is regulated by its
CC nucleotide bound state. In the ATP-bound form, it has a low
CC affinity for substrate proteins. However, upon hydrolysis of the
CC ATP to ADP, it undergoes a conformational change that increases
CC its affinity for substrate proteins. It goes through repeated
CC cycles of ATP hydrolysis and nucleotide exchange, which permits
CC cycles of substrate binding and release. The co-chaperones are of
CC three types: J-domain co-chaperones such as HSP40s (stimulate
CC ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF)
CC such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-
CC bound to the ATP-bound state thereby promoting substrate release),
CC and the TPR domain chaperones such as HOPX and STUB1
CC (PubMed:24012426, PubMed:26865365, PubMed:24318877). Maintains
CC protein homeostasis during cellular stress through two opposing
CC mechanisms: protein refolding and degradation. Its
CC acetylation/deacetylation state determines whether it functions in
CC protein refolding or protein degradation by controlling the
CC competitive binding of co-chaperones HOPX and STUB1. During the
CC early stress response, the acetylated form binds to HOPX which
CC assists in chaperone-mediated protein refolding, thereafter, it is
CC deacetylated and binds to ubiquitin ligase STUB1 that promotes
CC ubiquitin-mediated protein degradation (PubMed:27708256).
CC Regulates centrosome integrity during mitosis, and is required for
CC the maintenance of a functional mitotic centrosome that supports
CC the assembly of a bipolar mitotic spindle (PubMed:27137183).
CC Enhances STUB1-mediated SMAD3 ubiquitination and degradation and
CC facilitates STUB1-mediated inhibition of TGF-beta signaling
CC (PubMed:24613385). Essential for STUB1-mediated ubiquitination and
CC degradation of FOXP3 in regulatory T-cells (Treg) during
CC inflammation (PubMed:23973223). Negatively regulates heat shock-
CC induced HSF1 transcriptional activity during the attenuation and
CC recovery phase period of the heat shock response (PubMed:9499401).
CC {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223,
CC ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385,
CC ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256,
CC ECO:0000269|PubMed:9499401, ECO:0000303|PubMed:24012426,
CC ECO:0000303|PubMed:26865365}.
CC -!- FUNCTION: (Microbial infection) In case of rotavirus A infection,
CC serves as a post-attachment receptor for the virus to facilitate
CC entry into the cell. {ECO:0000269|PubMed:16537599}.
CC -!- SUBUNIT: Component of the CatSper complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs (PubMed:17289661). Interacts with CHCHD3, DNAJC7, IRAK1BP1,
CC PPP5C and TSC2 (PubMed:21081504, PubMed:12853476, PubMed:18620420,
CC PubMed:17233114, PubMed:15383005, PubMed:15963462). Interacts with
CC TERT; the interaction occurs in the absence of the RNA component,
CC TERC, and dissociates once the TERT complex has formed
CC (PubMed:11274138). Interacts with TRIM5 (via B30.2/SPRY domain)
CC (PubMed:20053985). Interacts with METTL21A (PubMed:23921388).
CC Interacts with DNAAF2 (By similarity). Interacts with PRKN
CC (PubMed:24270810). Interacts with FOXP3 (PubMed:23973223).
CC Interacts with NOD2; the interaction enhances NOD2 stability
CC (PubMed:24790089). Interacts with DNAJC9 (via J domain)
CC (PubMed:17182002). Interacts with ATF5; the interaction protects
CC ATF5 from degradation via proteasome-dependent and caspase-
CC dependent processes (PubMed:22528486). Interacts with RNF207 (via
CC the C-terminus); this interaction additively increases KCNH2
CC expression (PubMed:25281747). Interacts with HSF1 (via
CC transactivation domain); this interaction results in the
CC inhibition of heat shock- and HSF1-induced transcriptional
CC activity during the attenuation and recovery phase period of the
CC heat shock response (PubMed:7935376, PubMed:9499401). Interacts
CC with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the
CC non-acetylated form interact with HOPX and STUB1 respectively
CC (PubMed:27708256). Interacts with NEDD1 (PubMed:27137183).
CC Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105
CC (PubMed:24318877). Interacts with SMAD3 (PubMed:24613385).
CC {ECO:0000250|UniProtKB:Q61696, ECO:0000269|PubMed:10216320,
CC ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12853476,
CC ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:15963462,
CC ECO:0000269|PubMed:17182002, ECO:0000269|PubMed:17233114,
CC ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:18620420,
CC ECO:0000269|PubMed:20053985, ECO:0000269|PubMed:20072699,
CC ECO:0000269|PubMed:20179333, ECO:0000269|PubMed:20223214,
CC ECO:0000269|PubMed:21081504, ECO:0000269|PubMed:22528486,
CC ECO:0000269|PubMed:23921388, ECO:0000269|PubMed:23973223,
CC ECO:0000269|PubMed:24270810, ECO:0000269|PubMed:24318877,
CC ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:24790089,
CC ECO:0000269|PubMed:25281747, ECO:0000269|PubMed:27137183,
CC ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:7935376,
CC ECO:0000269|PubMed:9499401}.
CC -!- INTERACTION:
CC Q9NUX5:POT1; NbExp=2; IntAct=EBI-11052499, EBI-752420;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17289661}.
CC Nucleus {ECO:0000269|PubMed:27137183}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:27137183}. Note=Localized in cytoplasmic mRNP
CC granules containing untranslated mRNAs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P0DMV8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P0DMV8-2; Sequence=VSP_044427;
CC -!- INDUCTION: By heat shock.
CC -!- DOMAIN: The N-terminal nucleotide binding domain (NBD) (also known
CC as the ATPase domain) is responsible for binding and hydrolyzing
CC ATP. The C-terminal substrate-binding domain (SBD) (also known as
CC peptide-binding domain) binds to the client/substrate proteins.
CC The two domains are allosterically coupled so that, when ATP is
CC bound to the NBD, the SBD binds relatively weakly to clients. When
CC ADP is bound in the NBD, a conformational change enhances the
CC affinity of the SBD for client proteins.
CC {ECO:0000305|PubMed:24012426, ECO:0000305|PubMed:26865365}.
CC -!- PTM: In response to cellular stress, acetylated at Lys-77 by NA110
CC and then gradually deacetylated by HDAC4 at later stages.
CC Acetylation enhances its chaperone activity and also determines
CC whether it will function as a chaperone for protein refolding or
CC degradation by controlling its binding to co-chaperones HOPX and
CC STUB1. The acetylated form and the non-acetylated form bind to
CC HOPX and STUB1 respectively. Acetylation also protects cells
CC against various types of cellular stress.
CC {ECO:0000269|PubMed:27708256}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa1a/";
CC -----------------------------------------------------------------------
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DR EMBL; M11717; AAA52697.1; -; Genomic_DNA.
DR EMBL; M59828; AAA63226.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63300.1; -; Genomic_DNA.
DR EMBL; AF134726; AAD21816.1; -; Genomic_DNA.
DR EMBL; AK304652; BAG65428.1; -; mRNA.
DR EMBL; DQ451402; ABD96830.1; -; Genomic_DNA.
DR EMBL; AL671762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002453; AAH02453.1; -; mRNA.
DR EMBL; M24743; AAA59844.1; -; Genomic_DNA.
DR EMBL; X04676; CAA28381.1; -; Genomic_DNA.
DR EMBL; X04677; CAA28382.1; -; Genomic_DNA.
DR CCDS; CCDS34414.1; -. [P0DMV8-1]
DR PIR; A29160; A29160.
DR PIR; A45871; A45871.
DR PIR; I59139; I59139.
DR PIR; I79540; I79540.
DR RefSeq; NP_005336.3; NM_005345.5. [P0DMV8-1]
DR RefSeq; NP_005337.2; NM_005346.4. [P0DMV8-1]
DR UniGene; Hs.274402; -.
DR UniGene; Hs.702139; -.
DR UniGene; Hs.719966; -.
DR UniGene; Hs.743411; -.
DR PDB; 1HJO; X-ray; 2.30 A; A=3-382.
DR PDB; 1S3X; X-ray; 1.84 A; A=1-382.
DR PDB; 1XQS; X-ray; 2.90 A; C/D=184-371.
DR PDB; 2E88; X-ray; 1.80 A; A=1-388.
DR PDB; 2E8A; X-ray; 1.77 A; A=1-388.
DR PDB; 2LMG; NMR; -; A=537-610.
DR PDB; 3A8Y; X-ray; 2.30 A; A/B=1-388.
DR PDB; 3ATU; X-ray; 1.65 A; A=1-388.
DR PDB; 3ATV; X-ray; 1.58 A; A=1-388.
DR PDB; 3AY9; X-ray; 1.75 A; A=1-388.
DR PDB; 3D2E; X-ray; 2.35 A; B/D=1-382.
DR PDB; 3D2F; X-ray; 2.30 A; B/D=1-382.
DR PDB; 3JXU; X-ray; 2.14 A; A=1-387.
DR PDB; 3LOF; X-ray; 2.40 A; A/B/C/D/E/F=534-641.
DR PDB; 3Q49; X-ray; 1.54 A; C=634-641.
DR PDB; 4IO8; X-ray; 2.58 A; A=1-382.
DR PDB; 4J8F; X-ray; 2.70 A; A=1-382.
DR PDB; 4PO2; X-ray; 2.00 A; A/B=386-613.
DR PDB; 4WV5; X-ray; 2.04 A; A/B=395-543.
DR PDB; 4WV7; X-ray; 2.42 A; A/B=395-543.
DR PDB; 5AQW; X-ray; 1.53 A; A=1-380.
DR PDB; 5AQX; X-ray; 2.12 A; A=1-380.
DR PDB; 5AQY; X-ray; 1.56 A; A=1-380.
DR PDB; 5AQZ; X-ray; 1.65 A; A=1-380.
DR PDB; 5AR0; X-ray; 1.90 A; A=1-380.
DR PDB; 5BN8; X-ray; 1.34 A; A=1-388.
DR PDB; 5BN9; X-ray; 1.69 A; A=1-388.
DR PDB; 5BPL; X-ray; 1.93 A; A=1-388.
DR PDB; 5BPM; X-ray; 1.83 A; A=1-388.
DR PDB; 5BPN; X-ray; 2.10 A; A=1-388.
DR PDB; 5MKR; X-ray; 1.87 A; A=1-380.
DR PDB; 5MKS; X-ray; 1.99 A; A=1-380.
DR PDBsum; 1HJO; -.
DR PDBsum; 1S3X; -.
DR PDBsum; 1XQS; -.
DR PDBsum; 2E88; -.
DR PDBsum; 2E8A; -.
DR PDBsum; 2LMG; -.
DR PDBsum; 3A8Y; -.
DR PDBsum; 3ATU; -.
DR PDBsum; 3ATV; -.
DR PDBsum; 3AY9; -.
DR PDBsum; 3D2E; -.
DR PDBsum; 3D2F; -.
DR PDBsum; 3JXU; -.
DR PDBsum; 3LOF; -.
DR PDBsum; 3Q49; -.
DR PDBsum; 4IO8; -.
DR PDBsum; 4J8F; -.
DR PDBsum; 4PO2; -.
DR PDBsum; 4WV5; -.
DR PDBsum; 4WV7; -.
DR PDBsum; 5AQW; -.
DR PDBsum; 5AQX; -.
DR PDBsum; 5AQY; -.
DR PDBsum; 5AQZ; -.
DR PDBsum; 5AR0; -.
DR PDBsum; 5BN8; -.
DR PDBsum; 5BN9; -.
DR PDBsum; 5BPL; -.
DR PDBsum; 5BPM; -.
DR PDBsum; 5BPN; -.
DR PDBsum; 5MKR; -.
DR PDBsum; 5MKS; -.
DR ProteinModelPortal; P0DMV8; -.
DR SMR; P0DMV8; -.
DR IntAct; P0DMV8; 14.
DR MINT; MINT-96699; -.
DR BindingDB; P0DMV8; -.
DR ChEMBL; CHEMBL5460; -.
DR iPTMnet; P0DMV8; -.
DR PhosphoSitePlus; P0DMV8; -.
DR SwissPalm; P0DMV8; -.
DR DMDM; 147744565; -.
DR REPRODUCTION-2DPAGE; IPI00304925; -.
DR PeptideAtlas; P0DMV8; -.
DR PRIDE; P0DMV8; -.
DR DNASU; 3303; -.
DR Ensembl; ENST00000375651; ENSP00000364802; ENSG00000204389. [P0DMV8-1]
DR Ensembl; ENST00000400040; ENSP00000382915; ENSG00000215328.
DR Ensembl; ENST00000430065; ENSP00000404524; ENSG00000235941. [P0DMV8-1]
DR Ensembl; ENST00000433487; ENSP00000408907; ENSG00000234475. [P0DMV8-1]
DR Ensembl; ENST00000441618; ENSP00000406359; ENSG00000237724. [P0DMV8-1]
DR GeneID; 3303; -.
DR GeneID; 3304; -.
DR KEGG; hsa:3303; -.
DR KEGG; hsa:3304; -.
DR CTD; 3303; -.
DR CTD; 3304; -.
DR GeneCards; HSPA1A; -.
DR H-InvDB; HIX0058169; -.
DR H-InvDB; HIX0058187; -.
DR H-InvDB; HIX0166160; -.
DR HGNC; HGNC:5232; HSPA1A.
DR HPA; CAB017451; -.
DR HPA; CAB032815; -.
DR HPA; HPA052504; -.
DR MIM; 140550; gene.
DR MIM; 603012; gene.
DR neXtProt; NX_P0DMV8; -.
DR OpenTargets; ENSG00000204388; -.
DR OpenTargets; ENSG00000204389; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR KO; K03283; -.
DR OrthoDB; EOG093705LK; -.
DR PhylomeDB; P0DMV8; -.
DR TreeFam; TF105042; -.
DR Reactome; R-HSA-168330; Viral RNP Complexes in the Host Cell Nucleus.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-3371568; Attenuation phase.
DR Reactome; R-HSA-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SIGNOR; P0DMV8; -.
DR ChiTaRS; HSPA1A; human.
DR ChiTaRS; HSPA1B; human.
DR GeneWiki; HSPA1A; -.
DR PRO; PR:P0DMV8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR CleanEx; HS_HSPA1A; -.
DR ExpressionAtlas; P0DMV8; baseline and differential.
DR GO; GO:0016235; C:aggresome; IDA:UniProtKB.
DR GO; GO:0072562; C:blood microparticle; IDA:UniProtKB.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0030529; C:intracellular ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0016887; F:ATPase activity; IDA:BHF-UCL.
DR GO; GO:0042623; F:ATPase activity, coupled; IDA:UniProtKB.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; IPI:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; IDA:BHF-UCL.
DR GO; GO:0031249; F:denatured protein binding; IPI:CAFA.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0001664; F:G-protein coupled receptor binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR GO; GO:0044183; F:protein binding involved in protein folding; IDA:BHF-UCL.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0005102; F:receptor binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA: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:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0046034; P:ATP metabolic process; IDA:BHF-UCL.
DR GO; GO:0070370; P:cellular heat acclimation; IMP:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; TAS:ParkinsonsUK-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:CAFA.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:UniProtKB.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0097201; P:negative regulation of transcription from RNA polymerase II promoter in response to stress; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR GO; GO:1902380; P:positive regulation of endoribonuclease activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; IMP:UniProtKB.
DR GO; GO:1904722; P:positive regulation of mRNA endonucleolytic cleavage involved in unfolded protein response; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0042026; P:protein refolding; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:CAFA.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0006986; P:response to unfolded protein; IDA:UniProtKB.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C.
DR InterPro; IPR029047; HSP70_peptide-bd.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 1.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Chaperone; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Host cell receptor for virus entry;
KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Receptor; Reference proteome; Stress response.
FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330}.
FT CHAIN 2 641 Heat shock 70 kDa protein 1A.
FT /FTId=PRO_0000078249.
FT NP_BIND 12 15 ATP.
FT NP_BIND 202 204 ATP.
FT NP_BIND 268 275 ATP.
FT NP_BIND 339 342 ATP.
FT REGION 2 386 Nucleotide-binding domain (NBD).
FT {ECO:0000250|UniProtKB:P11142}.
FT REGION 394 509 Substrate-binding domain (SBD).
FT {ECO:0000250|UniProtKB:P11142}.
FT BINDING 71 71 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT {ECO:0000244|PubMed:19413330}.
FT MOD_RES 77 77 N6-acetyllysine.
FT {ECO:0000269|PubMed:27708256}.
FT MOD_RES 108 108 N6-acetyllysine.
FT {ECO:0000244|PubMed:19608861}.
FT MOD_RES 246 246 N6-acetyllysine.
FT {ECO:0000244|PubMed:19608861}.
FT MOD_RES 348 348 N6-acetyllysine.
FT {ECO:0000244|PubMed:19608861}.
FT MOD_RES 469 469 Omega-N-methylarginine.
FT {ECO:0000244|PubMed:24129315}.
FT MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A;
FT alternate. {ECO:0000244|PubMed:24129315,
FT ECO:0000269|PubMed:23349634,
FT ECO:0000269|PubMed:23921388}.
FT MOD_RES 561 561 N6,N6-dimethyllysine; alternate.
FT {ECO:0000244|PubMed:24129315}.
FT MOD_RES 631 631 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 633 633 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 636 636 Phosphothreonine.
FT {ECO:0000244|PubMed:20068231}.
FT VAR_SEQ 96 150 Missing (in isoform 2).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_044427.
FT VARIANT 110 110 E -> D (in dbSNP:rs562047).
FT {ECO:0000269|PubMed:14656967,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_029053.
FT MUTAGEN 10 10 D->A: Reduces affinity for ADP.
FT {ECO:0000269|PubMed:21608060}.
FT MUTAGEN 77 77 K->Q: No loss of acetylation and ATPase
FT activity. Exhibits normal protein
FT refolding activity during the early phase
FT but exhibits defects in ubiquitin-
FT mediated protein degradation during the
FT later phase.
FT {ECO:0000269|PubMed:27708256}.
FT MUTAGEN 77 77 K->R: Significant loss of acetylation and
FT ATPase activity. Decreased binding to
FT HOPX and HSP90 and increased binding to
FT STUB1 and NAA10. Impaired capacity for
FT protein refolding during the early phase
FT after stress but shows normal protein
FT degradation activity in the late phase.
FT {ECO:0000269|PubMed:27708256}.
FT MUTAGEN 199 199 D->A: Reduces affinity for ADP.
FT {ECO:0000269|PubMed:21608060}.
FT MUTAGEN 561 561 K->R: Complete loss of in vitro
FT methylation by METTL21A.
FT {ECO:0000269|PubMed:23349634,
FT ECO:0000269|PubMed:23921388}.
FT CONFLICT 7 7 I -> V (in Ref. 1; AAA52697 and 10;
FT CAA28381). {ECO:0000305}.
FT CONFLICT 355 355 N -> D (in Ref. 5; BAG65428).
FT {ECO:0000305}.
FT CONFLICT 370 370 A -> G (in Ref. 1; AAA52697).
FT {ECO:0000305}.
FT CONFLICT 469 469 Missing (in Ref. 1; AAA52697).
FT {ECO:0000305}.
FT CONFLICT 497 497 K -> N (in Ref. 5; BAG65428).
FT {ECO:0000305}.
FT STRAND 7 10 {ECO:0000244|PDB:5BN8}.
FT STRAND 13 22 {ECO:0000244|PDB:5BN8}.
FT STRAND 25 28 {ECO:0000244|PDB:5BN8}.
FT STRAND 36 39 {ECO:0000244|PDB:5BN8}.
FT STRAND 42 44 {ECO:0000244|PDB:5BN8}.
FT STRAND 49 51 {ECO:0000244|PDB:5BN8}.
FT HELIX 53 56 {ECO:0000244|PDB:5BN8}.
FT TURN 57 61 {ECO:0000244|PDB:5BN8}.
FT HELIX 63 65 {ECO:0000244|PDB:5BN8}.
FT HELIX 70 72 {ECO:0000244|PDB:5BN8}.
FT TURN 73 75 {ECO:0000244|PDB:5BN8}.
FT HELIX 81 86 {ECO:0000244|PDB:5BN8}.
FT HELIX 87 89 {ECO:0000244|PDB:5BN8}.
FT STRAND 91 97 {ECO:0000244|PDB:5BN8}.
FT STRAND 100 107 {ECO:0000244|PDB:5BN8}.
FT STRAND 110 114 {ECO:0000244|PDB:5BN8}.
FT HELIX 116 135 {ECO:0000244|PDB:5BN8}.
FT STRAND 141 146 {ECO:0000244|PDB:5BN8}.
FT HELIX 152 164 {ECO:0000244|PDB:5BN8}.
FT STRAND 168 174 {ECO:0000244|PDB:5BN8}.
FT HELIX 175 182 {ECO:0000244|PDB:5BN8}.
FT HELIX 185 187 {ECO:0000244|PDB:5BN8}.
FT STRAND 193 200 {ECO:0000244|PDB:5BN8}.
FT STRAND 205 213 {ECO:0000244|PDB:5BN8}.
FT STRAND 216 225 {ECO:0000244|PDB:5BN8}.
FT HELIX 230 249 {ECO:0000244|PDB:5BN8}.
FT HELIX 253 255 {ECO:0000244|PDB:5BPN}.
FT HELIX 257 274 {ECO:0000244|PDB:5BN8}.
FT STRAND 277 288 {ECO:0000244|PDB:5BN8}.
FT STRAND 291 298 {ECO:0000244|PDB:5BN8}.
FT HELIX 299 305 {ECO:0000244|PDB:5BN8}.
FT HELIX 307 312 {ECO:0000244|PDB:5BN8}.
FT HELIX 314 324 {ECO:0000244|PDB:5BN8}.
FT HELIX 328 330 {ECO:0000244|PDB:5BN8}.
FT STRAND 333 338 {ECO:0000244|PDB:5BN8}.
FT HELIX 339 342 {ECO:0000244|PDB:5BN8}.
FT HELIX 344 353 {ECO:0000244|PDB:5BN8}.
FT TURN 354 356 {ECO:0000244|PDB:5BN8}.
FT TURN 365 367 {ECO:0000244|PDB:5BN8}.
FT HELIX 368 380 {ECO:0000244|PDB:5BN8}.
FT HELIX 534 553 {ECO:0000244|PDB:3LOF}.
FT HELIX 564 583 {ECO:0000244|PDB:3LOF}.
FT HELIX 589 608 {ECO:0000244|PDB:3LOF}.
FT TURN 609 611 {ECO:0000244|PDB:3LOF}.
FT STRAND 637 639 {ECO:0000244|PDB:3Q49}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 9 16 ipat:HSP70_1 [T]
FT MYHIT 334 348 ipat:HSP70_3 [T]
FT MYHIT 6 611 ipfam:HSP70 [T]
FT MYHIT 197 210 ipat:HSP70_2 [T]
SQ SEQUENCE 641 AA; 70052 MW; 78F513118C96DE66 CRC64;
MAKAAAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
LNPQNTVFDA KRLIGRKFGD PVVQSDMKHW PFQVINDGDK PKVQVSYKGE TKAFYPEEIS
SMVLTKMKEI AEAYLGYPVT NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTAAA
IAYGLDRTGK GERNVLIFDL GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVNH
FVEEFKRKHK KDISQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
RFEELCSDLF RSTLEPVEKA LRDAKLDKAQ IHDLVLVGGS TRIPKVQKLL QDFFNGRDLN
KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS LGLETAGGVM TALIKRNSTI
PTKQTQIFTT YSDNQPGVLI QVYEGERAMT KDNNLLGRFE LSGIPPAPRG VPQIEVTFDI
DANGILNVTA TDKSTGKANK ITITNDKGRL SKEEIERMVQ EAEKYKAEDE VQRERVSAKN
ALESYAFNMK SAVEDEGLKG KISEADKKKV LDKCQEVISW LDANTLAEKD EFEHKRKELE
QVCNPIISGL YQGAGGPGPG GFGAQGPKGG SGSGPTIEEV D
//
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