RBCC Red Blood Cell Collection

HSP90AA1 (HSP90A, HSPC1, HSPCA) [Confidence: high (present in two of the MS resources)]
Heat shock protein HSP 90-alpha (Heat shock 86 kDa; HSP 86; HSP86; Renal carcinoma antigen NY-REN-38)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00328602
IPI00328602 heat shock 90kDa protein 1, alpha heat shock 90kDa protein 1, alpha membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoplasmic n/a expected molecular weight found in band > 188 kDa together with ubiquitin

UniProt P07900
ID HS90A_HUMAN Reviewed; 732 AA.
AC P07900; A8K500; B3KPJ9; Q2PP14; Q5CAQ6; Q5CAQ7; Q9BVQ5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 5.
DT 22-JAN-2014, entry version 187.
DE RecName: Full=Heat shock protein HSP 90-alpha;
DE AltName: Full=Heat shock 86 kDa;
DE Short=HSP 86;
DE Short=HSP86;
DE AltName: Full=Renal carcinoma antigen NY-REN-38;
GN Name=HSP90AA1; Synonyms=HSP90A, HSPC1, HSPCA;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=2780322; DOI=10.1093/nar/17.17.7108;
RA Soeda E., Yokoyama K., Yamazaki M., Akaogi K., Miwa T., Imai T.;
RT "Nucleotide sequence of a full-length cDNA for 90 kDa heat-shock
RT protein from human peripheral blood lymphocytes.";
RL Nucleic Acids Res. 17:7108-7108(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1368637;
RA Yamazaki M., Tashiro H., Yokoyama K., Soeda E.;
RT "Molecular cloning of cDNA encoding a human heat-shock protein whose
RT expression is induced by adenovirus type 12 E1A in HeLa cells.";
RL Agric. Biol. Chem. 54:3163-3170(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=2527334;
RA Hickey E., Brandon S.E., Smale G., Lloyd D., Weber L.A.;
RT "Sequence and regulation of a gene encoding a human 89-kilodalton heat
RT shock protein.";
RL Mol. Cell. Biol. 9:2615-2626(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND NOMENCLATURE.
RX PubMed=16269234; DOI=10.1016/j.ygeno.2005.08.012;
RA Chen B., Piel W.H., Gui L., Bruford E., Monteiro A.;
RT "The HSP90 family of genes in the human genome: insights into their
RT divergence and evolution.";
RL Genomics 86:627-637(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, and Teratocarcinoma;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-312.
RX PubMed=2469626; DOI=10.1016/0378-1119(88)90182-5;
RA Hoffmann T., Hovemann B.;
RT "Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related
RT genes encode formerly identified tumour-specific transplantation
RT antigens.";
RL Gene 74:491-501(1988).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-312.
RX PubMed=2591742; DOI=10.1016/0378-1119(89)90408-3;
RA Walter T., Drabent B., Krebs H., Tomalak M., Heiss S., Benecke B.J.J.;
RT "Cloning and analysis of a human 86-kDa heat-shock-protein-encoding
RT gene.";
RL Gene 83:105-115(1989).
RN [11]
RP PROTEIN SEQUENCE OF 101-112; 210-224; 300-314; 328-338; 346-355;
RP 387-400; 465-478 AND 633-647, AND 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 [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-732.
RC TISSUE=Placenta;
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 [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 539-732.
RC TISSUE=Heart;
RA Tanaka M., Tanaka T., Mitsui Y., Yamamoto M., Wood J.N.;
RT "The analysis of the genes reactive to monoclonal antibody, CE5.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PROTEIN SEQUENCE OF 2-21, AND PHOSPHORYLATION.
RX PubMed=2492519;
RA Lees-Miller S.P., Anderson C.W.;
RT "Two human 90-kDa heat shock proteins are phosphorylated in vivo at
RT conserved serines that are phosphorylated in vitro by casein kinase
RT II.";
RL J. Biol. Chem. 264:2431-2437(1989).
RN [15]
RP PROTEIN SEQUENCE OF 592-612, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS
RP OF CYS-598, AND S-NITROSYLATION AT CYS-598.
RX PubMed=15937123; DOI=10.1073/pnas.0407294102;
RA Martinez-Ruiz A., Villanueva L., Gonzalez de Orduna C.,
RA Lopez-Ferrer D., Higueras M.A., Tarin C., Rodriguez-Crespo I.,
RA Vazquez J., Lamas S.;
RT "S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and
RT endothelial nitric oxide synthase regulatory activities.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8525-8530(2005).
RN [16]
RP PHOSPHORYLATION AT THR-5 AND THR-7.
RX PubMed=2507541;
RA Lees-Miller S.P., Anderson C.W.;
RT "The human double-stranded DNA-activated protein kinase phosphorylates
RT the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal
RT threonine residues.";
RL J. Biol. Chem. 264:17275-17280(1989).
RN [17]
RP HOMODIMERIZATION.
RX PubMed=8289821;
RA Minami Y., Kimura Y., Kawasaki H., Suzuki K., Yahara I.;
RT "The carboxy-terminal region of mammalian HSP90 is required for its
RT dimerization and function in vivo.";
RL Mol. Cell. Biol. 14:1459-1464(1994).
RN [18]
RP SUBUNIT.
RX PubMed=7588731; DOI=10.1111/j.1432-1033.1995.001_1.x;
RA Nemoto T., Ohara-Nemoto Y., Ota M., Takagi T., Yokoyama K.;
RT "Mechanism of dimer formation of the 90-kDa heat-shock protein.";
RL Eur. J. Biochem. 233:1-8(1995).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4; PPID; PPP5C OR
RP STIP1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
RN [20]
RP INTERACTION WITH TOM34.
RX PubMed=9660753; DOI=10.1074/jbc.273.29.18007;
RA Young J.C., Obermann W.M., Hartl F.U.;
RT "Specific binding of tetratricopeptide repeat proteins to the C-
RT terminal 12-kDa domain of hsp90.";
RL J. Biol. Chem. 273:18007-18010(1998).
RN [21]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [22]
RP INTERACTION WITH TERT, AND FUNCTION AS A CO-CHAPERONE IN TELOMERASE
RP HOLOENZYME ASSEMBLY.
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 [23]
RP INTERACTION WITH HSF1.
RX PubMed=11583998; DOI=10.1074/jbc.M105931200;
RA Guo Y., Guettouche T., Fenna M., Boellmann F., Pratt W.B., Toft D.O.,
RA Smith D.F., Voellmy R.;
RT "Evidence for a mechanism of repression of heat shock factor 1
RT transcriptional activity by a multichaperone complex.";
RL J. Biol. Chem. 276:45791-45799(2001).
RN [24]
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 [25]
RP INTERACTION WITH AHSA1.
RX PubMed=12604615; DOI=10.1074/jbc.M212761200;
RA Lotz G.P., Lin H., Harst A., Obermann W.M.J.;
RT "Aha1 binds to the middle domain of Hsp90, contributes to client
RT protein activation, and stimulates the ATPase activity of the
RT molecular chaperone.";
RL J. Biol. Chem. 278:17228-17235(2003).
RN [26]
RP INTERACTION WITH SMYD3.
RX PubMed=15235609; DOI=10.1038/ncb1151;
RA Hamamoto R., Furukawa Y., Morita M., Iimura Y., Silva F.P., Li M.,
RA Yagyu R., Nakamura Y.;
RT "SMYD3 encodes a histone methyltransferase involved in the
RT proliferation of cancer cells.";
RL Nat. Cell Biol. 6:731-740(2004).
RN [27]
RP INTERACTION WITH PPP5C, AND 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 [28]
RP FUNCTION, AND INTERACTION WITH PPP5C.
RX PubMed=15577939; DOI=10.1038/sj.emboj.7600496;
RA Yang J., Roe S.M., Cliff M.J., Williams M.A., Ladbury J.E.,
RA Cohen P.T., Barford D.;
RT "Molecular basis for TPR domain-mediated regulation of protein
RT phosphatase 5.";
RL EMBO J. 24:1-10(2005).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-263, AND
RP MASS SPECTROMETRY.
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND MASS
RP SPECTROMETRY.
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [31]
RP INTERACTION WITH PPP5C.
RX PubMed=16531226; DOI=10.1016/j.str.2005.12.009;
RA Cliff M.J., Harris R., Barford D., Ladbury J.E., Williams M.A.;
RT "Conformational diversity in the TPR domain-mediated interaction of
RT protein phosphatase 5 with Hsp90.";
RL Structure 14:415-426(2006).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252 AND SER-263, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND MASS
RP SPECTROMETRY.
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 [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-263, AND
RP MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [37]
RP IDENTIFICATION BY MASS 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 [38]
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 [39]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-443; LYS-458; LYS-489 AND
RP LYS-585, AND MASS SPECTROMETRY.
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 [40]
RP INTERACTION WITH CHORDC1.
RX PubMed=19875381; DOI=10.1074/mcp.M900261-MCP200;
RA Gano J.J., Simon J.A.;
RT "A proteomic investigation of ligand-dependent HSP90 complexes reveals
RT CHORDC1 as a novel ADP-dependent HSP90-interacting protein.";
RL Mol. Cell. Proteomics 9:255-270(2010).
RN [41]
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 [42]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA 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 [43]
RP INTERACTION WITH FNIP1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17028174; DOI=10.1073/pnas.0603781103;
RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L.,
RA Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III,
RA Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr.,
RA Linehan W.M., Schmidt L.S., Zbar B.;
RT "Folliculin encoded by the BHD gene interacts with a binding protein,
RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006).
RN [44]
RP MUTAGENESIS OF GLY-97.
RX PubMed=18256191; DOI=10.1242/dev.018150;
RA Hawkins T.A., Haramis A.P., Etard C., Prodromou C., Vaughan C.K.,
RA Ashworth R., Ray S., Behra M., Holder N., Talbot W.S., Pearl L.H.,
RA Strahle U., Wilson S.W.;
RT "The ATPase-dependent chaperoning activity of Hsp90a regulates thick
RT filament formation and integration during skeletal muscle
RT myofibrillogenesis.";
RL Development 135:1147-1156(2008).
RN [45]
RP MUTAGENESIS OF CYS-598.
RX PubMed=19696785; DOI=10.1038/embor.2009.153;
RA Retzlaff M., Stahl M., Eberl H.C., Lagleder S., Beck J., Kessler H.,
RA Buchner J.;
RT "Hsp90 is regulated by a switch point in the C-terminal domain.";
RL EMBO Rep. 10:1147-1153(2009).
RN [46]
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [47]
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 [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 11-223 IN COMPLEX WITH
RP GELDANAMYCIN.
RX PubMed=9108479; DOI=10.1016/S0092-8674(00)80203-2;
RA Stebbins C.E., Russo A.A., Schneider C., Rosen N., Hartl F.U.,
RA Pavletich N.P.;
RT "Crystal structure of an Hsp90-geldanamycin complex: targeting of a
RT protein chaperone by an antitumor agent.";
RL Cell 89:239-250(1997).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 11-223 IN COMPLEX WITH ADP,
RP CATALYTIC ACTIVITY, AND INTERACTION WITH PTGES3.
RX PubMed=9817749; DOI=10.1083/jcb.143.4.901;
RA Obermann W.M., Sondermann H., Russo A.A., Pavletich N.P., Hartl F.U.;
RT "In vivo function of Hsp90 is dependent on ATP binding and ATP
RT hydrolysis.";
RL J. Cell Biol. 143:901-910(1998).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 724-732 IN COMPLEX WITH
RP STUB1, AND INTERACTION WITH STUB1 AND UBE2N.
RX PubMed=16307917; DOI=10.1016/j.molcel.2005.09.023;
RA Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C.,
RA Pearl L.H.;
RT "Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3
RT ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.";
RL Mol. Cell 20:525-538(2005).
CC -!- FUNCTION: Molecular chaperone that promotes the maturation,
CC structural maintenance and proper regulation of specific target
CC proteins involved for instance in cell cycle control and signal
CC transduction. Undergoes a functional cycle that is linked to its
CC ATPase activity. This cycle probably induces conformational
CC changes in the client proteins, thereby causing their activation.
CC Interacts dynamically with various co-chaperones that modulate its
CC substrate recognition, ATPase cycle and chaperone function.
CC -!- SUBUNIT: Homodimer. Identified in NR3C1/GCR steroid receptor-
CC chaperone complexes formed at least by NR3C1, HSP90AA1 and a
CC variety of proteins containing TPR repeats such as FKBP4, FKBP5,
CC PPID, PPP5C STIP1. Interacts with AHSA1, FNIP1, HSF1, SMYD3 and
CC TOM34. Interacts with TERT; the interaction, together with PTGES3,
CC is required for correct assembly and stabilization of the TERT
CC holoenzyme complex. Interacts with CHORDC1 and DNAJC7. Interacts
CC with STUB1 and UBE2N; may couple the chaperone and ubiquitination
CC systems. Interacts (via TPR repeat-binding motif) with PPP5C (via
CC TPR repeats); the interaction is direct and activates PPP5C
CC phosphatase activity.
CC -!- INTERACTION:
CC Self; NbExp=4; IntAct=EBI-296047, EBI-296047;
CC O95433:AHSA1; NbExp=4; IntAct=EBI-296047, EBI-448610;
CC Q96G23:CERS2; NbExp=2; IntAct=EBI-296047, EBI-1057080;
CC Q9UHD1:CHORDC1; NbExp=8; IntAct=EBI-296047, EBI-2550959;
CC P00533:EGFR; NbExp=3; IntAct=EBI-296047, EBI-297353;
CC Q02790:FKBP4; NbExp=8; IntAct=EBI-296047, EBI-1047444;
CC Q14318:FKBP8; NbExp=7; IntAct=EBI-296047, EBI-724839;
CC P05412:JUN; NbExp=2; IntAct=EBI-296047, EBI-852823;
CC P26882:PPID (xeno); NbExp=4; IntAct=EBI-296047, EBI-6477155;
CC P53041:PPP5C; NbExp=8; IntAct=EBI-296047, EBI-716663;
CC Q15185:PTGES3; NbExp=5; IntAct=EBI-296047, EBI-1049387;
CC P61247:RPS3A; NbExp=2; IntAct=EBI-296047, EBI-352378;
CC P35467:S100a1 (xeno); NbExp=4; IntAct=EBI-296047, EBI-6477109;
CC Q9UNE7:STUB1; NbExp=9; IntAct=EBI-296047, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=HSP90AA1-1, HSP90-alpha 2;
CC IsoId=P07900-1; Sequence=Displayed;
CC Name=2; Synonyms=HSP90AA1-2;
CC IsoId=P07900-2; Sequence=VSP_026604;
CC Note=Variant in position: 71:M->L (in dbSNP:rs8005905);
CC -!- DOMAIN: The TPR repeat-binding motif mediates interaction with TPR
CC repeat-containing proteins like the co-chaperone STUB1.
CC -!- PTM: ISGylated.
CC -!- PTM: S-nitrosylated; negatively regulates the ATPase activity and
CC the activation of eNOS by HSP90AA1.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family.
CC -----------------------------------------------------------------------
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DR EMBL; X15183; CAA33259.1; -; mRNA.
DR EMBL; M27024; AAA63194.1; -; Genomic_DNA.
DR EMBL; AJ890082; CAI64495.1; -; mRNA.
DR EMBL; AJ890083; CAI64496.1; -; mRNA.
DR EMBL; DQ314871; ABC40730.1; -; Genomic_DNA.
DR EMBL; AK056446; BAG51711.1; -; mRNA.
DR EMBL; AK291115; BAF83804.1; -; mRNA.
DR EMBL; AK291607; BAF84296.1; -; mRNA.
DR EMBL; AL133223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81765.1; -; Genomic_DNA.
DR EMBL; X07270; CAA30255.1; -; mRNA.
DR EMBL; M30626; AAA36023.1; -; Genomic_DNA.
DR EMBL; BC000987; AAH00987.1; -; mRNA.
DR EMBL; BC121062; AAI21063.1; -; mRNA.
DR EMBL; D87666; BAA13430.1; -; mRNA.
DR EMBL; D87666; BAA13431.1; -; mRNA.
DR PIR; A32319; HHHU86.
DR RefSeq; NP_001017963.2; NM_001017963.2.
DR RefSeq; NP_005339.3; NM_005348.3.
DR UniGene; Hs.525600; -.
DR PDB; 1BYQ; X-ray; 1.50 A; A=9-236.
DR PDB; 1OSF; X-ray; 1.75 A; A=9-223.
DR PDB; 1UY6; X-ray; 1.90 A; A=1-236.
DR PDB; 1UY7; X-ray; 1.90 A; A=1-236.
DR PDB; 1UY8; X-ray; 1.98 A; A=1-236.
DR PDB; 1UY9; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYC; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYD; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYE; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYF; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYG; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYH; X-ray; 2.20 A; A=1-236.
DR PDB; 1UYI; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYK; X-ray; 2.00 A; A=1-236.
DR PDB; 1UYL; X-ray; 1.40 A; A=1-236.
DR PDB; 1YC1; X-ray; 1.70 A; A=9-235.
DR PDB; 1YC3; X-ray; 2.12 A; A=9-235.
DR PDB; 1YC4; X-ray; 1.81 A; A=9-235.
DR PDB; 1YER; X-ray; 1.65 A; A=9-236.
DR PDB; 1YES; X-ray; 2.20 A; A=9-236.
DR PDB; 1YET; X-ray; 1.90 A; A=9-236.
DR PDB; 2BSM; X-ray; 2.05 A; A=2-235.
DR PDB; 2BT0; X-ray; 1.90 A; A/B=2-235.
DR PDB; 2BUG; NMR; -; B=-.
DR PDB; 2BYH; X-ray; 1.90 A; A=11-235.
DR PDB; 2BYI; X-ray; 1.60 A; A=11-235.
DR PDB; 2BZ5; X-ray; 1.90 A; A/B=2-235.
DR PDB; 2C2L; X-ray; 3.30 A; E/F/G/H=724-732.
DR PDB; 2CCS; X-ray; 1.79 A; A=1-236.
DR PDB; 2CCT; X-ray; 2.30 A; A=1-236.
DR PDB; 2CCU; X-ray; 2.70 A; A=1-236.
DR PDB; 2CDD; X-ray; 1.90 A; A/B=1-236.
DR PDB; 2FWY; X-ray; 2.10 A; A=1-236.
DR PDB; 2FWZ; X-ray; 2.10 A; A=1-236.
DR PDB; 2H55; X-ray; 2.00 A; A=1-236.
DR PDB; 2JJC; X-ray; 1.95 A; A=9-223.
DR PDB; 2K5B; NMR; -; A=14-223.
DR PDB; 2QF6; X-ray; 3.10 A; A/B/C/D=17-223.
DR PDB; 2QFO; X-ray; 1.68 A; A/B=17-223.
DR PDB; 2QG0; X-ray; 1.85 A; A/B=17-223.
DR PDB; 2QG2; X-ray; 1.80 A; A=17-223.
DR PDB; 2UWD; X-ray; 1.90 A; A=2-235.
DR PDB; 2VCI; X-ray; 2.00 A; A=1-236.
DR PDB; 2VCJ; X-ray; 2.50 A; A=1-236.
DR PDB; 2WI1; X-ray; 2.30 A; A=1-236.
DR PDB; 2WI2; X-ray; 2.09 A; A/B=1-236.
DR PDB; 2WI3; X-ray; 1.90 A; A=1-236.
DR PDB; 2WI4; X-ray; 2.40 A; A=1-236.
DR PDB; 2WI5; X-ray; 2.10 A; A=1-236.
DR PDB; 2WI6; X-ray; 2.18 A; A=1-236.
DR PDB; 2WI7; X-ray; 2.50 A; A=1-236.
DR PDB; 2XAB; X-ray; 1.90 A; A/B=9-236.
DR PDB; 2XDK; X-ray; 1.97 A; A=9-236.
DR PDB; 2XDL; X-ray; 1.98 A; A=9-236.
DR PDB; 2XDS; X-ray; 1.97 A; A=9-236.
DR PDB; 2XDU; X-ray; 1.74 A; A=14-224.
DR PDB; 2XDX; X-ray; 2.42 A; A=9-236.
DR PDB; 2XHR; X-ray; 2.20 A; A=9-236.
DR PDB; 2XHT; X-ray; 2.27 A; A=9-236.
DR PDB; 2XHX; X-ray; 2.80 A; A=9-236.
DR PDB; 2XJG; X-ray; 2.25 A; A=9-236.
DR PDB; 2XJJ; X-ray; 1.90 A; A/B=9-236.
DR PDB; 2XJX; X-ray; 1.66 A; A=9-236.
DR PDB; 2XK2; X-ray; 1.95 A; A=9-236.
DR PDB; 2YE2; X-ray; 1.90 A; A=9-236.
DR PDB; 2YE3; X-ray; 1.95 A; A=9-236.
DR PDB; 2YE4; X-ray; 2.30 A; A=9-236.
DR PDB; 2YE5; X-ray; 1.73 A; A=9-236.
DR PDB; 2YE6; X-ray; 2.56 A; A=9-236.
DR PDB; 2YE7; X-ray; 2.20 A; A=9-236.
DR PDB; 2YE8; X-ray; 2.30 A; A=9-236.
DR PDB; 2YE9; X-ray; 2.20 A; A=9-236.
DR PDB; 2YEA; X-ray; 1.73 A; A=9-236.
DR PDB; 2YEB; X-ray; 2.40 A; A=9-236.
DR PDB; 2YEC; X-ray; 2.10 A; A=9-236.
DR PDB; 2YED; X-ray; 2.10 A; A=9-236.
DR PDB; 2YEE; X-ray; 2.30 A; A=9-236.
DR PDB; 2YEF; X-ray; 1.55 A; A=9-236.
DR PDB; 2YEG; X-ray; 2.50 A; A/B=9-236.
DR PDB; 2YEH; X-ray; 2.10 A; A=9-236.
DR PDB; 2YEI; X-ray; 2.20 A; A=9-236.
DR PDB; 2YEJ; X-ray; 2.20 A; A=9-236.
DR PDB; 2YI0; X-ray; 1.60 A; A=1-229.
DR PDB; 2YI5; X-ray; 2.50 A; A=1-229.
DR PDB; 2YI6; X-ray; 1.80 A; A=1-229.
DR PDB; 2YI7; X-ray; 1.40 A; A=1-229.
DR PDB; 2YJW; X-ray; 1.61 A; A=18-223.
DR PDB; 2YJX; X-ray; 1.83 A; A=18-223.
DR PDB; 2YK2; X-ray; 1.74 A; A=18-223.
DR PDB; 2YK9; X-ray; 1.32 A; A=18-223.
DR PDB; 2YKB; X-ray; 1.93 A; A=18-223.
DR PDB; 2YKC; X-ray; 1.67 A; A=18-223.
DR PDB; 2YKE; X-ray; 1.43 A; A=18-223.
DR PDB; 2YKI; X-ray; 1.67 A; A=18-223.
DR PDB; 2YKJ; X-ray; 1.46 A; A=18-223.
DR PDB; 3B24; X-ray; 1.70 A; A/B=9-236.
DR PDB; 3B25; X-ray; 1.75 A; A=9-236.
DR PDB; 3B26; X-ray; 2.10 A; A/B=9-236.
DR PDB; 3B27; X-ray; 1.50 A; A=9-236.
DR PDB; 3B28; X-ray; 1.35 A; A/B=9-236.
DR PDB; 3BM9; X-ray; 1.60 A; A=14-236.
DR PDB; 3BMY; X-ray; 1.60 A; A=14-236.
DR PDB; 3D0B; X-ray; 1.74 A; A=1-232.
DR PDB; 3EKO; X-ray; 1.55 A; A/B=9-225.
DR PDB; 3EKR; X-ray; 2.00 A; A/B=9-225.
DR PDB; 3FT5; X-ray; 1.90 A; A=9-236.
DR PDB; 3FT8; X-ray; 2.00 A; A=9-236.
DR PDB; 3HEK; X-ray; 1.95 A; A/B=9-225.
DR PDB; 3HHU; X-ray; 1.59 A; A/B=1-224.
DR PDB; 3HYY; X-ray; 1.90 A; A=9-236.
DR PDB; 3HYZ; X-ray; 2.30 A; A/B=9-236.
DR PDB; 3HZ1; X-ray; 2.30 A; A=9-236.
DR PDB; 3HZ5; X-ray; 1.90 A; A=9-236.
DR PDB; 3INW; X-ray; 1.95 A; A=10-236.
DR PDB; 3INX; X-ray; 1.75 A; A=10-236.
DR PDB; 3K97; X-ray; 1.95 A; A=9-236.
DR PDB; 3K98; X-ray; 2.40 A; A/B=9-225.
DR PDB; 3K99; X-ray; 2.10 A; A/B/C/D=9-225.
DR PDB; 3MNR; X-ray; 1.90 A; P=1-232.
DR PDB; 3O0I; X-ray; 1.47 A; A=1-236.
DR PDB; 3OW6; X-ray; 1.80 A; A=17-223.
DR PDB; 3OWB; X-ray; 2.05 A; A=17-223.
DR PDB; 3OWD; X-ray; 1.63 A; A=17-223.
DR PDB; 3Q6M; X-ray; 3.00 A; A/B/C=293-732.
DR PDB; 3Q6N; X-ray; 3.05 A; A/B/C/D/E/F=293-732.
DR PDB; 3QDD; X-ray; 1.79 A; A=1-236.
DR PDB; 3QTF; X-ray; 1.57 A; A=14-236.
DR PDB; 3R4M; X-ray; 1.70 A; A=9-236.
DR PDB; 3R4N; X-ray; 2.00 A; A/B=9-225.
DR PDB; 3R4O; X-ray; 2.65 A; A/B=9-225.
DR PDB; 3R4P; X-ray; 1.70 A; A/B=9-225.
DR PDB; 3R91; X-ray; 1.58 A; A=14-236.
DR PDB; 3R92; X-ray; 1.58 A; A=14-236.
DR PDB; 3RKZ; X-ray; 1.57 A; A=14-236.
DR PDB; 3RLP; X-ray; 1.70 A; A/B=9-225.
DR PDB; 3RLQ; X-ray; 1.90 A; A/B=9-225.
DR PDB; 3RLR; X-ray; 1.70 A; A/B=9-225.
DR PDB; 3T0H; X-ray; 1.20 A; A=9-236.
DR PDB; 3T0Z; X-ray; 2.19 A; A=9-236.
DR PDB; 3T10; X-ray; 1.24 A; A=9-236.
DR PDB; 3T1K; X-ray; 1.50 A; A/B=9-236.
DR PDB; 3T2S; X-ray; 1.50 A; A/B=9-236.
DR PDB; 3TUH; X-ray; 1.80 A; A/B=16-224.
DR PDB; 3VHA; X-ray; 1.39 A; A=9-236.
DR PDB; 3VHC; X-ray; 1.41 A; A=9-236.
DR PDB; 3VHD; X-ray; 1.52 A; A/B=9-236.
DR PDB; 4AIF; X-ray; 2.01 A; D/E=726-732.
DR PDB; 4AWO; X-ray; 1.70 A; A/B=9-236.
DR PDB; 4AWP; X-ray; 1.82 A; A/B=9-236.
DR PDB; 4AWQ; X-ray; 1.60 A; A/B=9-236.
DR PDB; 4B7P; X-ray; 1.70 A; A=9-236.
DR PDB; 4BQJ; X-ray; 2.00 A; A=9-236.
DR PDB; 4EEH; X-ray; 1.60 A; A=9-236.
DR PDB; 4EFT; X-ray; 2.12 A; A=9-236.
DR PDB; 4EFU; X-ray; 2.00 A; A=9-236.
DR PDB; 4EGH; X-ray; 1.60 A; A=9-236.
DR PDB; 4EGI; X-ray; 1.79 A; A=9-236.
DR PDB; 4EGK; X-ray; 1.69 A; A=9-236.
DR PDB; 4FCP; X-ray; 2.00 A; A/B=1-236.
DR PDB; 4FCQ; X-ray; 2.15 A; A=1-236.
DR PDB; 4FCR; X-ray; 1.70 A; A=1-236.
DR PDB; 4HY6; X-ray; 1.65 A; A=9-236.
DR PDB; 4JQL; X-ray; 1.72 A; A=9-236.
DR PDBsum; 1BYQ; -.
DR PDBsum; 1OSF; -.
DR PDBsum; 1UY6; -.
DR PDBsum; 1UY7; -.
DR PDBsum; 1UY8; -.
DR PDBsum; 1UY9; -.
DR PDBsum; 1UYC; -.
DR PDBsum; 1UYD; -.
DR PDBsum; 1UYE; -.
DR PDBsum; 1UYF; -.
DR PDBsum; 1UYG; -.
DR PDBsum; 1UYH; -.
DR PDBsum; 1UYI; -.
DR PDBsum; 1UYK; -.
DR PDBsum; 1UYL; -.
DR PDBsum; 1YC1; -.
DR PDBsum; 1YC3; -.
DR PDBsum; 1YC4; -.
DR PDBsum; 1YER; -.
DR PDBsum; 1YES; -.
DR PDBsum; 1YET; -.
DR PDBsum; 2BSM; -.
DR PDBsum; 2BT0; -.
DR PDBsum; 2BUG; -.
DR PDBsum; 2BYH; -.
DR PDBsum; 2BYI; -.
DR PDBsum; 2BZ5; -.
DR PDBsum; 2C2L; -.
DR PDBsum; 2CCS; -.
DR PDBsum; 2CCT; -.
DR PDBsum; 2CCU; -.
DR PDBsum; 2CDD; -.
DR PDBsum; 2FWY; -.
DR PDBsum; 2FWZ; -.
DR PDBsum; 2H55; -.
DR PDBsum; 2JJC; -.
DR PDBsum; 2K5B; -.
DR PDBsum; 2QF6; -.
DR PDBsum; 2QFO; -.
DR PDBsum; 2QG0; -.
DR PDBsum; 2QG2; -.
DR PDBsum; 2UWD; -.
DR PDBsum; 2VCI; -.
DR PDBsum; 2VCJ; -.
DR PDBsum; 2WI1; -.
DR PDBsum; 2WI2; -.
DR PDBsum; 2WI3; -.
DR PDBsum; 2WI4; -.
DR PDBsum; 2WI5; -.
DR PDBsum; 2WI6; -.
DR PDBsum; 2WI7; -.
DR PDBsum; 2XAB; -.
DR PDBsum; 2XDK; -.
DR PDBsum; 2XDL; -.
DR PDBsum; 2XDS; -.
DR PDBsum; 2XDU; -.
DR PDBsum; 2XDX; -.
DR PDBsum; 2XHR; -.
DR PDBsum; 2XHT; -.
DR PDBsum; 2XHX; -.
DR PDBsum; 2XJG; -.
DR PDBsum; 2XJJ; -.
DR PDBsum; 2XJX; -.
DR PDBsum; 2XK2; -.
DR PDBsum; 2YE2; -.
DR PDBsum; 2YE3; -.
DR PDBsum; 2YE4; -.
DR PDBsum; 2YE5; -.
DR PDBsum; 2YE6; -.
DR PDBsum; 2YE7; -.
DR PDBsum; 2YE8; -.
DR PDBsum; 2YE9; -.
DR PDBsum; 2YEA; -.
DR PDBsum; 2YEB; -.
DR PDBsum; 2YEC; -.
DR PDBsum; 2YED; -.
DR PDBsum; 2YEE; -.
DR PDBsum; 2YEF; -.
DR PDBsum; 2YEG; -.
DR PDBsum; 2YEH; -.
DR PDBsum; 2YEI; -.
DR PDBsum; 2YEJ; -.
DR PDBsum; 2YI0; -.
DR PDBsum; 2YI5; -.
DR PDBsum; 2YI6; -.
DR PDBsum; 2YI7; -.
DR PDBsum; 2YJW; -.
DR PDBsum; 2YJX; -.
DR PDBsum; 2YK2; -.
DR PDBsum; 2YK9; -.
DR PDBsum; 2YKB; -.
DR PDBsum; 2YKC; -.
DR PDBsum; 2YKE; -.
DR PDBsum; 2YKI; -.
DR PDBsum; 2YKJ; -.
DR PDBsum; 3B24; -.
DR PDBsum; 3B25; -.
DR PDBsum; 3B26; -.
DR PDBsum; 3B27; -.
DR PDBsum; 3B28; -.
DR PDBsum; 3BM9; -.
DR PDBsum; 3BMY; -.
DR PDBsum; 3D0B; -.
DR PDBsum; 3EKO; -.
DR PDBsum; 3EKR; -.
DR PDBsum; 3FT5; -.
DR PDBsum; 3FT8; -.
DR PDBsum; 3HEK; -.
DR PDBsum; 3HHU; -.
DR PDBsum; 3HYY; -.
DR PDBsum; 3HYZ; -.
DR PDBsum; 3HZ1; -.
DR PDBsum; 3HZ5; -.
DR PDBsum; 3INW; -.
DR PDBsum; 3INX; -.
DR PDBsum; 3K97; -.
DR PDBsum; 3K98; -.
DR PDBsum; 3K99; -.
DR PDBsum; 3MNR; -.
DR PDBsum; 3O0I; -.
DR PDBsum; 3OW6; -.
DR PDBsum; 3OWB; -.
DR PDBsum; 3OWD; -.
DR PDBsum; 3Q6M; -.
DR PDBsum; 3Q6N; -.
DR PDBsum; 3QDD; -.
DR PDBsum; 3QTF; -.
DR PDBsum; 3R4M; -.
DR PDBsum; 3R4N; -.
DR PDBsum; 3R4O; -.
DR PDBsum; 3R4P; -.
DR PDBsum; 3R91; -.
DR PDBsum; 3R92; -.
DR PDBsum; 3RKZ; -.
DR PDBsum; 3RLP; -.
DR PDBsum; 3RLQ; -.
DR PDBsum; 3RLR; -.
DR PDBsum; 3T0H; -.
DR PDBsum; 3T0Z; -.
DR PDBsum; 3T10; -.
DR PDBsum; 3T1K; -.
DR PDBsum; 3T2S; -.
DR PDBsum; 3TUH; -.
DR PDBsum; 3VHA; -.
DR PDBsum; 3VHC; -.
DR PDBsum; 3VHD; -.
DR PDBsum; 4AIF; -.
DR PDBsum; 4AWO; -.
DR PDBsum; 4AWP; -.
DR PDBsum; 4AWQ; -.
DR PDBsum; 4B7P; -.
DR PDBsum; 4BQJ; -.
DR PDBsum; 4EEH; -.
DR PDBsum; 4EFT; -.
DR PDBsum; 4EFU; -.
DR PDBsum; 4EGH; -.
DR PDBsum; 4EGI; -.
DR PDBsum; 4EGK; -.
DR PDBsum; 4FCP; -.
DR PDBsum; 4FCQ; -.
DR PDBsum; 4FCR; -.
DR PDBsum; 4HY6; -.
DR PDBsum; 4JQL; -.
DR ProteinModelPortal; P07900; -.
DR SMR; P07900; 15-699.
DR DIP; DIP-27595N; -.
DR IntAct; P07900; 141.
DR MINT; MINT-132070; -.
DR STRING; 9606.ENSP00000335153; -.
DR BindingDB; P07900; -.
DR ChEMBL; CHEMBL2095165; -.
DR DrugBank; DB00615; Rifabutin.
DR PhosphoSite; P07900; -.
DR DMDM; 92090606; -.
DR OGP; P07900; -.
DR REPRODUCTION-2DPAGE; IPI00784295; -.
DR PRIDE; P07900; -.
DR Ensembl; ENST00000216281; ENSP00000216281; ENSG00000080824.
DR Ensembl; ENST00000334701; ENSP00000335153; ENSG00000080824.
DR GeneID; 3320; -.
DR KEGG; hsa:3320; -.
DR UCSC; uc001yku.4; human.
DR CTD; 3320; -.
DR GeneCards; GC14M102547; -.
DR HGNC; HGNC:5253; HSP90AA1.
DR HPA; CAB002058; -.
DR MIM; 140571; gene.
DR neXtProt; NX_P07900; -.
DR PharmGKB; PA29519; -.
DR HOVERGEN; HBG007374; -.
DR InParanoid; P07900; -.
DR KO; K04079; -.
DR OMA; LTDSPAC; -.
DR OrthoDB; EOG780RM0; -.
DR PhylomeDB; P07900; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HSP90AA1; human.
DR EvolutionaryTrace; P07900; -.
DR GenomeRNAi; 3320; -.
DR NextBio; 13162; -.
DR PMAP-CutDB; P07900; -.
DR PRO; PR:P07900; -.
DR ArrayExpress; P07900; -.
DR Bgee; P07900; -.
DR CleanEx; HS_HSP90AA1; -.
DR Genevestigator; P07900; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; TAS:UniProtKB.
DR GO; GO:0016887; F:ATPase activity; IDA:UniProtKB.
DR GO; GO:0002135; F:CTP binding; IEA:Ensembl.
DR GO; GO:0032564; F:dATP binding; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0003729; F:mRNA binding; IEA:Ensembl.
DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; TAS:UniProtKB.
DR GO; GO:0030911; F:TPR domain binding; IDA:UniProtKB.
DR GO; GO:0002134; F:UTP binding; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0046209; P:nitric oxide metabolic process; TAS:Reactome.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Ensembl.
DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0033160; P:positive regulation of protein import into nucleus, translocation; IEA:Ensembl.
DR GO; GO:0045040; P:protein import into mitochondrial outer membrane; IDA:BHF-UCL.
DR GO; GO:0042026; P:protein refolding; TAS:UniProtKB.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
DR GO; GO:0043627; P:response to estrogen stimulus; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0009651; P:response to salt stress; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl.
DR Gene3D; 3.30.565.10; -; 2.
DR InterPro; IPR003594; HATPase_ATP-bd.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS00298; HSP90; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Chaperone; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Stress response; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 732 Heat shock protein HSP 90-alpha.
FT /FTId=PRO_0000062911.
FT REGION 682 732 Required for homodimerization.
FT MOTIF 728 732 TPR repeat-binding.
FT BINDING 51 51 ATP.
FT BINDING 93 93 ATP.
FT BINDING 112 112 ATP (By similarity).
FT BINDING 138 138 ATP; via amide nitrogen.
FT BINDING 400 400 ATP (By similarity).
FT MOD_RES 5 5 Phosphothreonine; by PRKDC.
FT MOD_RES 7 7 Phosphothreonine; by PRKDC.
FT MOD_RES 224 224 N6-acetyllysine.
FT MOD_RES 231 231 Phosphoserine.
FT MOD_RES 252 252 Phosphoserine.
FT MOD_RES 263 263 Phosphoserine.
FT MOD_RES 313 313 Phosphotyrosine (By similarity).
FT MOD_RES 399 399 Phosphoserine.
FT MOD_RES 410 410 N6-acetyllysine.
FT MOD_RES 443 443 N6-acetyllysine.
FT MOD_RES 458 458 N6-acetyllysine.
FT MOD_RES 489 489 N6-acetyllysine.
FT MOD_RES 492 492 Phosphotyrosine (By similarity).
FT MOD_RES 576 576 N6-acetyllysine.
FT MOD_RES 585 585 N6-acetyllysine.
FT MOD_RES 598 598 S-nitrosocysteine.
FT VAR_SEQ 1 1 M -> MPPCSGGDGSTPPGPSLRDRDCPAQSAEYPRDRLDP
FT RPGSPSEASSPPFLRSRAPVNWYQEKAQVFLWHLMVSGSTT
FT LLCLWKQPFHVSAFPVTASLAFRQSQGAGQHLYKDLQPFIL
FT LRLLM (in isoform 2).
FT /FTId=VSP_026604.
FT MUTAGEN 97 97 G->D: Abolishes ATPase activity.
FT MUTAGEN 598 598 C->A,N,D: Reduces ATPase activity and
FT client protein activation.
FT MUTAGEN 598 598 C->S: Loss of S-nitrosylation.
FT CONFLICT 63 63 S -> T (in Ref. 1; CAA33259).
FT CONFLICT 74 74 K -> R (in Ref. 4; CAI64495 and 6;
FT BAG51711).
FT CONFLICT 86 86 D -> G (in Ref. 4; CAI64495 and 6;
FT BAG51711).
FT STRAND 18 21
FT HELIX 24 35
FT HELIX 43 63
FT HELIX 67 70
FT STRAND 78 83
FT TURN 84 87
FT STRAND 88 93
FT HELIX 100 104
FT HELIX 106 108
FT HELIX 111 123
FT HELIX 128 134
FT HELIX 137 143
FT STRAND 145 153
FT STRAND 155 157
FT STRAND 159 164
FT STRAND 169 174
FT STRAND 181 190
FT HELIX 192 198
FT HELIX 200 210
FT STRAND 212 216
FT STRAND 218 220
FT TURN 221 224
FT STRAND 225 227
FT HELIX 228 230
FT HELIX 296 298
FT HELIX 306 317
FT STRAND 324 331
FT STRAND 333 335
FT STRAND 337 343
FT STRAND 361 365
FT STRAND 368 372
FT HELIX 380 382
FT STRAND 386 392
FT HELIX 408 427
FT HELIX 431 451
FT HELIX 453 455
FT HELIX 456 460
FT STRAND 464 467
FT TURN 468 472
FT HELIX 477 482
FT STRAND 490 495
FT HELIX 499 503
FT HELIX 506 508
FT HELIX 509 514
FT STRAND 518 521
FT HELIX 525 529
FT TURN 530 532
FT STRAND 539 543
FT HELIX 555 567
FT HELIX 569 578
FT HELIX 580 582
FT STRAND 584 588
FT STRAND 593 601
FT STRAND 603 605
FT HELIX 608 613
FT STRAND 632 636
FT HELIX 641 652
FT HELIX 657 673
FT HELIX 681 694
FT STRAND 728 730
SQ SEQUENCE 732 AA; 84660 MW; 969F65FCC0BC86FD CRC64;
MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR
YESLTDPSKL DSGKELHINL IPNKQDRTLT IVDTGIGMTK ADLINNLGTI AKSGTKAFME
ALQAGADISM IGQFGVGFYS AYLVAEKVTV ITKHNDDEQY AWESSAGGSF TVRTDTGEPM
GRGTKVILHL KEDQTEYLEE RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKED
KEEEKEKEEK ESEDKPEIED VGSDEEEEKK DGDKKKKKKI KEKYIDQEEL NKTKPIWTRN
PDDITNEEYG EFYKSLTNDW EDHLAVKHFS VEGQLEFRAL LFVPRRAPFD LFENRKKKNN
IKLYVRRVFI MDNCEELIPE YLNFIRGVVD SEDLPLNISR EMLQQSKILK VIRKNLVKKC
LELFTELAED KENYKKFYEQ FSKNIKLGIH EDSQNRKKLS ELLRYYTSAS GDEMVSLKDY
CTRMKENQKH IYYITGETKD QVANSAFVER LRKHGLEVIY MIEPIDEYCV QQLKEFEGKT
LVSVTKEGLE LPEDEEEKKK QEEKKTKFEN LCKIMKDILE KKVEKVVVSN RLVTSPCCIV
TSTYGWTANM ERIMKAQALR DNSTMGYMAA KKHLEINPDH SIIETLRQKA EADKNDKSVK
DLVILLYETA LLSSGFSLED PQTHANRIYR MIKLGLGIDE DDPTADDTSA AVTEEMPPLE
GDDDTSRMEE VD
//

MIM 140571
*RECORD*
*FIELD* NO
140571
*FIELD* TI
*140571 HEAT-SHOCK PROTEIN, 90-KD, ALPHA, CLASS A, MEMBER 1; HSP90AA1
;;HEAT-SHOCK 90-KD PROTEIN 1, ALPHA, FORMERLY; HSPCA, FORMERLY;;
read moreHSPC1;;
HSP90A;;
HSP89-ALPHA; HSP89A;;
HEAT-SHOCK 90-KD PROTEIN 1, ALPHA-LIKE 4; HSPCAL4;;
LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 2; LAP2;;
LPS-ASSOCIATED PROTEIN 2
*FIELD* TX

DESCRIPTION

HSP90 proteins are highly conserved molecular chaperones that have key
roles in signal transduction, protein folding, protein degradation, and
morphologic evolution. HSP90 proteins normally associate with other
cochaperones and play important roles in folding newly synthesized
proteins or stabilizing and refolding denatured proteins after stress.
There are 2 major cytosolic HSP90 proteins, HSP90AA1, an inducible form,
and HSP90AB1 (140572), a constitutive form. Other HSP90 proteins are
found in endoplasmic reticulum (HSP90B1; 191175) and mitochondria
(TRAP1; 606219) (Chen et al., 2005).

CLONING

In humans, 2 distinct HSP90 cDNA clones were identified that
hybrid-select different mRNA transcripts encoding 2 members of the HSP90
family. These were called HSP89-alpha and HSP89-beta (Hickey et al.,
1986; Simon et al., 1987).

By database analysis, Chen et al. (2005) identified several HSP90AA1
variants encoding proteins of 413, 635, 732, and 854 amino acids. Like
other HSP90 proteins, the 732-amino acid HSP90AA1 protein has a highly
conserved N-terminal domain, a charged domain, a middle domain involved
in ATPase activity, a second charged domain, and a C-terminal domain. It
also has a 4-helical cytokine motif, a gln-rich region, and a C-terminal
MEEVD motif characteristic of cytosolic HSP90 proteins. The 854-amino
acid HSP90AA1 isoform has an N-terminal extension compared with the
732-amino acid isoform, but is otherwise identical.

- Chimeric CD47/HSP90AA1 Transcript

By screening a T-lymphoblastic leukemia cell line (CEM) cDNA library
with a probe originally isolated from a pancreatic cancer cDNA library,
Schweinfest et al. (1998) cloned a variant of HSPCA that they designated
HSP89-alpha-delta-N. The deduced 539-amino acid variant protein has a
calculated molecular mass of about 63 kD. It has a unique 30-amino acid
N terminus instead of the 223-amino acid ATP/geldanamycin-binding domain
found at the N terminus of full-length HSPCA, which contains 732 amino
acids. RT-PCR analysis detected expression of the variant in CEM cells
and several pancreatic cell lines, as well as in normal pancreatic
tissue. In vitro transcription/translation produced a protein with an
apparent molecular mass of about 70 kD.

Chen et al. (2005) determined that the HSP89-alpha-delta-N transcript,
which they called HSP90N, is a chimera, with the first 105 bp of the
coding sequence derived from the CD47 gene (601028) on chromosome
3q13.2, and the remaining coding sequence derived from HSP90AA1.

GENE FUNCTION

Stepanova et al. (1996) found that CDC37 (605065) and HSP90 associate
preferentially with the fraction of CDK4 (123829) not bound to D-type
cyclins. Pharmacologic inactivation of CDC37/HSP90 function leads to
reduced stability of CDK4.

CD14 (158120) and lipopolysaccharide (LPS)-binding protein (LBP; 151990)
are major receptors for LPS; however, binding analyses and TNF
production assays have suggested the presence of additional cell surface
receptors, designated LPS-associated proteins (LAPs), that are distinct
from CD14, LBP, and the Toll-like receptors (see TLR4; 603030). Using
affinity chromatography, peptide mass fingerprinting, and fluorescence
resonance energy transfer, Triantafilou et al. (2001) identified 4
diverse proteins, heat-shock cognate protein (HSPA8; 600816), HSP90A,
chemokine receptor CXCR4 (162643), and growth/differentiation factor-5
(GDF5; 601146), on monocytes that form an activation cluster after LPS
ligation and are involved in LPS signal transduction. Antibody
inhibition analysis suggested that disruption of cluster formation
abrogates TNF release. Triantafilou et al. (2001) proposed that heat
shock proteins, which are highly conserved from bacteria to eukaryotic
cells, are remnants of an ancient system of antigen presentation and
defense against microbial pathogens.

Huntington disease (HD; 143100) is a progressive neurodegenerative
disorder with no effective treatment. Geldanamycin is a benzoquinone
ansamycin that binds to the heat-shock protein Hsp90 (Stebbins et al.,
1997) and activates a heat-shock response in mammalian cells. Sittler et
al. (2001) showed that treatment of mammalian cells with geldanamycin at
nanomolar concentrations induced the expression of Hsp40 (see 604572),
Hsp70 (see 140550), and Hsp90 and inhibited HD exon 1 protein
aggregation in a dose-dependent manner. Similar results were obtained by
overexpression of Hsp70 and Hsp40 in a separate cell culture model of
HD. The authors proposed that this may provide the basis for the
development of a novel pharmacotherapy for HD and related glutamine
repeat disorders.

Chen et al. (2002) identified CDC37 and HSP90 as 2 additional components
of the I-kappa-B kinase (IKK) complex. This complex also contains 2
catalytic subunits, IKK-alpha (600664) and IKK-beta (603258), and a
regulatory subunit, NEMO (300248).

Morphologic alterations occur in Drosophila melanogaster when function
of Hsp90 is compromised during development. Genetic selection maintains
the altered phenotypes in subsequent generations (Rutherford and
Lindquist, 1998). Queitsch et al. (2002) showed, however, that
phenotypic variation still occurs in nearly isogenic recombinant inbred
strains of Arabidopsis thaliana. Using a D. melanogaster strain with a
dominant allele of the segmentation gene Kruppel, Sollars et al. (2003)
confirmed this finding and presented evidence supporting an epigenetic
mechanism for Hsp90's capacitor function, whereby reduced activity of
Hsp90 induces a heritably altered chromatin state. The altered chromatin
state is evidenced by ectopic expression of the morphogen 'wingless' in
eye imaginal discs and a corresponding abnormal eye phenotype, both of
which are epigenetically heritable in subsequent generations, even when
function of Hsp90 is restored. Mutations in 9 different genes of the
trithorax group that encode chromatin-remodeling proteins also induced
the abnormal phenotype. These findings suggested that Hsp90 acts as a
capacitor for morphologic evolution through epigenetic and genetic
mechanisms. Rutherford and Henikoff (2003) commented that the evidence
that heritable epigenetic variation is common raises questions about the
contribution of epigenetic variation to quantitative traits in general.
They stated that the nature of quantitative-trait variation is one of
the last unexplored frontiers in genetics.

Young et al. (2003) showed that the cytosolic chaperones HSP90 and HSP70
dock onto a specialized tetratricopeptide (TPR) domain in the import
receptor TOMM70 (606081) at the outer mitochondrial membrane. This
interaction served to deliver a set of preproteins to the receptor for
subsequent membrane translocation dependent on the HSP90 ATPase.
Disruption of the chaperone/TOMM70 recognition inhibited the import of
these preproteins into mitochondria. Young et al. (2003) proposed a
mechanism in which chaperones are recruited for a specific targeting
event by a membrane-bound receptor.

HSP90 is a molecular chaperone that plays a key role in the
conformational maturation of oncogenic signaling proteins, including
HER2/ERBB2 (164870), AKT (164730), RAF1 (164760), BCR-ABL (151410), and
mutated p53 (191170). HSP90 inhibitors bind to HSP90, and induce the
proteasomal degradation of HSP90 client proteins. Although HSP90 is
highly expressed in most cells, HSP90 inhibitors selectively kill cancer
cells compared to normal cells, and the HSP90 inhibitor
17-allylaminogeldanamycin (17-AAG) exhibited antitumor activity in
preclinical models (Solit et al., 2002). Kamal et al. (2003) reported
that HSP90 derived from tumor cells has a 100-fold higher binding
affinity for 17-AAG than does HSP90 from normal cells. Tumor HSP90 is
present entirely in multichaperone complexes with high ATPase activity,
whereas HSP90 from normal tissues is in a latent, uncomplexed state. In
vitro reconstitution of chaperone complexes with HSP90 resulted in
increased binding affinity to 17-AAG, and increased ATPase activity.
Kamal et al. (2003) concluded that their results suggested that tumor
cells contain HSP90 complexes in an activated, high-affinity
conformation that facilitates malignant progression, and that may
represent a unique target for cancer therapeutics.

Ficker et al. (2003) demonstrated that the cytosolic chaperones HSP70
and HSP90 interact directly with the core-glycosylated form of the
wildtype HERG (152427) gene product (the alpha subunit of the I(Kr)
cardiac potassium channel) present in the ER, but not the fully
glycosylated, cell surface form. Trafficking-deficient mutants remained
tightly associated with HSP70 and HSP90 in the ER, whereas a
nonfunctional but trafficking HERG was released from the chaperones
during maturation, comparable to the wildtype. Ficker et al. (2003)
concluded that HSP90 and HSP70 are crucial for the maturation of
wildtype HERG as well as the retention of trafficking-deficient HERG
mutants.

Eustace et al. (2004) identified HSP90 as an important extracellular
mediator of cancer cell invasion. HSP90A, but not HSP90B (140572), was
expressed extracellularly on fibrosarcoma and breast cancer cells.
HSP90A interacted with MMP2 (120360) outside the cell and promoted MMP2
activation, which is critical for tumor invasiveness.

To investigate whether the expression of telomerase subunits, of which
HSP90 is one, is reflected in the malignant transition of
pheochromocytomas, Boltze et al. (2003) determined mRNA and/or protein
expression in 28 benign and 9 malignant pheochromocytomas and compared
the results with telomerase activity. HSP90 was increased in malignant
pheochromocytomas, but was also expressed at a lower level in benign
tumors. TERT (187270) was clearly associated with aggressive biologic
behavior. The authors concluded that TERT, HSP90, and telomerase
activity are upregulated in malignant cells of the adrenal medulla.

Using recombinant human and bovine proteins for pull-down assays, Okada
et al. (2004) showed that the Ca(2+)-binding protein S100A1 (176940),
but not calmodulin (see CALM1, 114180), interacted with heat-shock
chaperone components HSP90, HSP70, FKBP52 (FKBP4; 600611), and CYP40
(PPID; 601753). Coimmunoprecipitation studies confirmed the
interactions. S100A1 contributed to protein refolding in the HSP70/HSP90
multichaperone complex.

Nitric oxide (NO) is a paracrine mediator of vascular and platelet
function that is produced in the vasculature by NO synthase-3 (NOS3;
163729). Using human platelets, Ji et al. (2007) demonstrated that
polymerization of beta-actin (ACTB; 102630) regulated the activation
state of NOS3, and hence NO formation, by altering its binding to HSP90.
NOS3 bound the globular, but not the filamentous, form of beta-actin,
and the affinity of NOS3 for globular beta-actin was, in turn, increased
by HSP90. Formation of this ternary complex of NOS3, globular
beta-actin, and HSP90 increased NOS activity and cyclic GMP, an index of
bioactive NO, and increased the rate of HSP90 degradation, thus limiting
NOS3 activation. Ji et al. (2007) concluded that beta-actin regulates NO
formation and signaling in platelets.

Ruden et al. (2005) reviewed the transgenerational epigenetic effects
mediated by Hsp90 inhibition and diethylstilbesterol (DES). They
proposed that transgenerational epigenetic phenomena involving Hsp90 and
DES are related and that chromatin-mediated WNT (WNT1; 164820) signaling
modifications are required for both. The authors suggested that
inhibitors of Hsp90, WNT signaling, and chromatin-remodeling enzymes
might function as anticancer agents by interfering with epigenetic
reprogramming and canalization in cancer stem cells.

Some heat-shock proteins, such as HSP90, can be antiapoptotic and are
the targets of anticancer drugs. Increased IP6K2 (606992) activity
sensitizes cancer cells to stressors, whereas its depletion blocks cell
death. Using mouse tissues and human cell lines, Chakraborty et al.
(2008) showed that HSP90 physiologically bound IP6K2 and inhibited its
catalytic activity. Drugs and selective mutations that abolished
HSP90-IP6K2 binding elicited activation of IP6K2, leading to cell death.
Chakraborty et al. (2008) concluded that the prosurvival actions of
HSP90 reflect inhibition of IP6K2 signaling.

Cerchietti et al. (2009) showed that endogenous HSP90 interacted
directly with BCL6 (109565) in diffuse large B-cell lymphomas (DLBCLs)
and stabilized BCL6 mRNA and protein. HSP90 and BCL6 were almost
invariantly coexpressed in the nuclei of primary DLBCL cells. HSP90
formed a complex with BCL6 at BCL6 target promoters, and pharmacologic
inhibition of HSP90 derepressed BCL6 target genes.

Okiyoneda et al. (2010) identified the components of the peripheral
protein quality control network that removes unfolded CFTR containing
the F508del mutation (602421.0001) from the plasma membrane. Based on
their results and proteostatic mechanisms at different subcellular
locations, Okiyoneda et al. (2010) proposed a model in which the
recognition of unfolded cytoplasmic regions of CFTR is mediated by HSC70
(600816) in concert with DNAJA1 (602837) and possibly by the HSP90
machinery. Prolonged interaction with the chaperone-cochaperone complex
recruits CHIP (607207)-UBCH5C (602963) and leads to ubiquitination of
conformationally damaged CFTR. This ubiquitination is probably
influenced by other E3 ligases and deubiquitinating enzyme activities,
culminating in accelerated endocytosis and lysosomal delivery mediated
by Ub-binding clathrin adaptors and the endosomal sorting complex
required for transport (ESCRT) machinery, respectively. In an
accompanying perspective, Hutt and Balch (2010) commented that the
'yin-yang' balance maintained by the proteostasis network is critical
for normal cellular, tissue, and organismal physiology.

Canalization, or developmental robustness, is an organism's ability to
produce the same phenotype despite genotypic variations and
environmental influences. Expression of a gain-of-function allele of
Drosophila Kruppel results in misregulation of genes in the fly eye disc
and generation of eye outgrowths, which are normally repressed via
canalization. Using a fly eye outgrowth assay, Gangaraju et al. (2011)
showed that a protein complex made up of Piwi (see 605571), Hsp83, and
Hop (STIP1; 605063) was involved in canalization. The results suggested
that canalization may involve Hsp83-mediated phosphorylation of Piwi.
Gangaraju et al. (2011) concluded that the eye outgrowth phenotype is a
defect in epigenetic silencing of a normally suppressed genotype.

GENE STRUCTURE

Chen et al. (2005) determined that the HSP90AA1 gene contains 15 exons.

MAPPING

Ozawa et al. (1992) used 2 previously isolated distinct cDNA clones for
HSP90-alpha--one from human peripheral blood lymphocytes and the other
from HeLa cells transfected with the adenovirus E1A gene--to determine
the organization of this gene family from 3 approaches: Southern
analysis of a panel of human/hamster somatic cell hybrids, molecular
cloning of cosmid clones from genomic DNA, and in situ hybridization.
They demonstrated nucleotide sequences corresponding to HSP90-alpha at 4
chromosome sites: 1q21.2-q22, 4q35, 11p14.2-14.1, and 14q32.3. These
were symbolized HSPCAL1, HSPCAL2, HSPCAL3, and HSPCAL4, respectively.
Which of these genes are functional was not determined. Jabs (1993)
indicated that the HSPCAL4 gene, which maps to chromosome 14q32, is
functional.

By genomic sequence analysis, Chen et al. (2005) mapped the HSP90AA1
gene to chromosome 14q32.32. They mapped a second functional HSP90AA
gene, HSP90AA2, to chromosome 11p14.1, and identified HSP90AA
pseudogenes on chromosomes 1q23.1 (HSP90AA3P), 4q35.2 (HSP90AA4P),
3q27.1 (HSP90AA5P), and 4q33 (HSP90AA6P).

NOMENCLATURE

Chen et al. (2005) provided a revised nomenclature system for the HSP90
gene family. Under this system, the root HSP90A indicates cytosolic
HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates
mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA
representing conventional HSP90-alpha, and HSP90AB representing
HSP90-beta. The number following the root/class represents the gene in
that class, and a 'P' at the end indicates a putative pseudogene.

*FIELD* SA
Rebbe et al. (1989)
*FIELD* RF
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3. Chakraborty, A.; Koldobskiy, M. A.; Sixt, K. M.; Juluri, K. R.;
Mustafa, A. K.; Snowman, A. M.; van Rossum, D. B.; Patterson, R. L.;
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6. Eustace, B. K.; Sakurai, T.; Stewart, J. K.; Yimlamai, D.; Unger,
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*FIELD* CN
Patricia A. Hartz - updated: 5/5/2011
Ada Hamosh - updated: 8/31/2010
Patricia A. Hartz - updated: 1/7/2010
Patricia A. Hartz - updated: 7/17/2009
Matthew B. Gross - updated: 8/12/2008
Patricia A. Hartz - updated: 3/13/2008
George E. Tiller - updated: 2/7/2008
Patricia A. Hartz - updated: 1/16/2008
John A. Phillips, III - updated: 7/8/2005
Patricia A. Hartz - updated: 5/20/2004
Patricia A. Hartz - updated: 3/10/2004
Marla J. F. O'Neill - updated: 3/3/2004
Ada Hamosh - updated: 9/26/2003
Stylianos E. Antonarakis - updated: 1/15/2003
Victor A. McKusick - updated: 12/31/2002
Victor A. McKusick - updated: 12/18/2002
Stylianos E. Antonarakis - updated: 9/23/2002
George E. Tiller - updated: 11/9/2001
Paul J. Converse - updated: 6/28/2001
Carol A. Bocchini - updated: 6/22/2000

*FIELD* CD
Victor A. McKusick: 12/29/1989

*FIELD* ED
alopez: 03/21/2013
terry: 8/6/2012
mgross: 5/5/2011
terry: 5/5/2011
alopez: 9/3/2010
terry: 8/31/2010
mgross: 1/19/2010
terry: 1/7/2010
terry: 12/16/2009
mgross: 8/19/2009
terry: 7/17/2009
alopez: 11/13/2008
mgross: 8/12/2008
mgross: 3/13/2008
wwang: 2/14/2008
terry: 2/7/2008
mgross: 1/25/2008
terry: 1/16/2008
alopez: 7/8/2005
alopez: 2/1/2005
alopez: 6/28/2004
mgross: 5/20/2004
mgross: 3/10/2004
terry: 3/10/2004
carol: 3/3/2004
alopez: 9/29/2003
terry: 9/26/2003
mgross: 1/15/2003
alopez: 12/31/2002
alopez: 12/18/2002
terry: 12/18/2002
mgross: 9/23/2002
terry: 3/8/2002
cwells: 11/21/2001
cwells: 11/9/2001
mgross: 6/28/2001
carol: 6/22/2000
terry: 7/24/1998
dkim: 7/21/1998
mark: 3/4/1997
warfield: 4/8/1994
carol: 11/3/1993
supermim: 3/16/1992
carol: 2/1/1992
carol: 11/8/1991
supermim: 3/20/1990