HS90A_MOUSE
ID HS90A_MOUSE Reviewed; 733 AA.
AC P07901;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Heat shock protein HSP 90-alpha {ECO:0000305};
DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P07900};
DE AltName: Full=Heat shock 86 kDa;
DE Short=HSP 86;
DE Short=HSP86;
DE AltName: Full=Tumor-specific transplantation 86 kDa antigen;
DE Short=TSTA;
GN Name=Hsp90aa1 {ECO:0000312|MGI:MGI:96250}; Synonyms=Hsp86, Hsp86-1, Hspca;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=2925609; DOI=10.1016/s0021-9258(18)83551-7;
RA Moore S.K., Kozak C., Robinson E.A., Ullrich S.J., Appella E.;
RT "Murine 86- and 84-kDa heat shock proteins, cDNA sequences, chromosome
RT assignments, and evolutionary origins.";
RL J. Biol. Chem. 264:5343-5351(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BALB/cJ;
RX PubMed=1916807; DOI=10.1016/0888-7543(91)90193-i;
RA Moore S.K., Appella E., Villar C.J., Kozak C.A.;
RT "Mapping of the mouse 86-kDa heat-shock protein expressed gene (Hsp86-1) on
RT chromosome 12 and related genes on chromosomes 3, 4, 9, and 11.";
RL Genomics 10:1019-1029(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-31.
RX PubMed=3458168; DOI=10.1073/pnas.83.10.3121;
RA Ullrich S.J., Robinson E.A., Law L.W., Willingham M., Appella E.;
RT "A mouse tumor-specific transplantation antigen is a heat shock-related
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3121-3125(1986).
RN [5]
RP PROTEIN SEQUENCE OF 2-12, AND HOMODIMERIZATION.
RX PubMed=8289821; DOI=10.1128/mcb.14.2.1459-1464.1994;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-356.
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 genes
RT encode formerly identified tumour-specific transplantation antigens.";
RL Gene 74:491-501(1988).
RN [7]
RP PROTEIN SEQUENCE OF 47-58; 61-69; 75-84; 88-112; 154-173; 186-201; 210-224;
RP 285-356; 369-401; 448-457; 491-511; 515-535; 548-561; 569-574; 593-632 AND
RP 634-648.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 460-733.
RX PubMed=2806771; DOI=10.1111/j.1432-0436.1989.tb00730.x;
RA Legagneux V., Mezger V., Quelard C., Barnier J.V., Bensaude O., Morange M.;
RT "High constitutive transcription of HSP86 gene in murine embryonal
RT carcinoma cells.";
RL Differentiation 41:42-48(1989).
RN [9]
RP INTERACTION WITH KSR1.
RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523;
RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.;
RT "Kinase suppressor of Ras forms a multiprotein signaling complex and
RT modulates MEK localization.";
RL Mol. Cell. Biol. 19:5523-5534(1999).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4; PPID; PPP5C OR 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 [11]
RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4.
RX PubMed=11278753; DOI=10.1074/jbc.m010809200;
RA Galigniana M.D., Radanyi C., Renoir J.-M., Housley P.R., Pratt W.B.;
RT "Evidence that the peptidylprolyl isomerase domain of the hsp90-binding
RT immunophilin FKBP52 is involved in both dynein interaction and
RT glucocorticoid receptor movement to the nucleus.";
RL J. Biol. Chem. 276:14884-14889(2001).
RN [12]
RP IDENTIFICATION IN A HETEROMULTIMERIC COMPLEX WITH NR3C1 AND FKBP4 OR FKBP5,
RP AND SUBCELLULAR LOCATION.
RX PubMed=11751894; DOI=10.1074/jbc.c100531200;
RA Davies T.H., Ning Y.M., Sanchez E.R.;
RT "A new first step in activation of steroid receptors: hormone-induced
RT switching of FKBP51 and FKBP52 immunophilins.";
RL J. Biol. Chem. 277:4597-4600(2002).
RN [13]
RP PHOSPHORYLATION AT THR-5 AND THR-7 BY PRKDC.
RX PubMed=2507541; DOI=10.1016/s0021-9258(18)71488-9;
RA Lees-Miller S.P., Anderson C.W.;
RT "The human double-stranded DNA-activated protein kinase phosphorylates the
RT 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine
RT residues.";
RL J. Biol. Chem. 264:17275-17280(1989).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-493, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-314, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; SER-263 AND SER-477, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP INTERACTION WITH ASL; ASS1 AND NOS2.
RX PubMed=22081021; DOI=10.1038/nm.2544;
RA Erez A., Nagamani S.C., Shchelochkov O.A., Premkumar M.H., Campeau P.M.,
RA Chen Y., Garg H.K., Li L., Mian A., Bertin T.K., Black J.O., Zeng H.,
RA Tang Y., Reddy A.K., Summar M., O'Brien W.E., Harrison D.G., Mitch W.E.,
RA Marini J.C., Aschner J.L., Bryan N.S., Lee B.;
RT "Requirement of argininosuccinate lyase for systemic nitric oxide
RT production.";
RL Nat. Med. 17:1619-1626(2011).
RN [23]
RP SUBCELLULAR LOCATION, INTERACTION WITH HECTD1, AND UBIQUITINATION.
RX PubMed=22431752; DOI=10.1083/jcb.201105101;
RA Sarkar A.A., Zohn I.E.;
RT "Hectd1 regulates intracellular localization and secretion of Hsp90 to
RT control cellular behavior of the cranial mesenchyme.";
RL J. Cell Biol. 196:789-800(2012).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-58 AND LYS-84, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [25]
RP INTERACTION WITH NR3C1 AND NR1D1, AND SUBCELLULAR LOCATION.
RX PubMed=27686098; DOI=10.1242/jcs.190959;
RA Okabe T., Chavan R., Fonseca Costa S.S., Brenna A., Ripperger J.A.,
RA Albrecht U.;
RT "REV-ERBalpha influences the stability and nuclear localization of the
RT glucocorticoid receptor.";
RL J. Cell Sci. 129:4143-4154(2016).
RN [26]
RP ACTIVITY REGULATION, AND INTERACTION WITH TSC1 AND AHSA1.
RX PubMed=29127155; DOI=10.15252/embj.201796700;
RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L.,
RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H.,
RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.;
RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding
RT of kinase and non-kinase clients.";
RL EMBO J. 36:3650-3665(2017).
RN [27]
RP INTERACTION WITH PDCL3, AND SUBCELLULAR LOCATION.
RX PubMed=27496612; DOI=10.1002/jcb.25669;
RA Krzemien-Ojak L., Goral A., Joachimiak E., Filipek A., Fabczak H.;
RT "Interaction of a Novel Chaperone PhLP2A With the Heat Shock Protein
RT Hsp90.";
RL J. Cell. Biochem. 118:420-429(2017).
CC -!- FUNCTION: Molecular chaperone that promotes the maturation, structural
CC maintenance and proper regulation of specific target proteins involved
CC for instance in cell cycle control and signal transduction. Undergoes a
CC functional cycle that is linked to its ATPase activity which is
CC essential for its chaperone activity. This cycle probably induces
CC conformational changes in the client proteins, thereby causing their
CC activation. Interacts dynamically with various co-chaperones that
CC modulate its substrate recognition, ATPase cycle and chaperone
CC function. Engages with a range of client protein classes via its
CC interaction with various co-chaperone proteins or complexes, that act
CC as adapters, simultaneously able to interact with the specific client
CC and the central chaperone itself. Recruitment of ATP and co-chaperone
CC followed by client protein forms a functional chaperone. After the
CC completion of the chaperoning process, properly folded client protein
CC and co-chaperone leave HSP90 in an ADP-bound partially open
CC conformation and finally, ADP is released from HSP90 which acquires an
CC open conformation for the next cycle. Plays a critical role in
CC mitochondrial import, delivers preproteins to the mitochondrial import
CC receptor TOMM70. Apart from its chaperone activity, it also plays a
CC role in the regulation of the transcription machinery. HSP90 and its
CC co-chaperones modulate transcription at least at three different
CC levels. In the first place, they alter the steady-state levels of
CC certain transcription factors in response to various physiological
CC cues. Second, they modulate the activity of certain epigenetic
CC modifiers, such as histone deacetylases or DNA methyl transferases, and
CC thereby respond to the change in the environment. Third, they
CC participate in the eviction of histones from the promoter region of
CC certain genes and thereby turn on gene expression. Binds bacterial
CC lipopolysaccharide (LPS) and mediates LPS-induced inflammatory
CC response, including TNF secretion by monocytes. Antagonizes STUB1-
CC mediated inhibition of TGF-beta signaling via inhibition of STUB1-
CC mediated SMAD3 ubiquitination and degradation. Mediates the association
CC of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which
CC promotes host antiviral response. {ECO:0000250|UniProtKB:P07900}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10;
CC Evidence={ECO:0000250|UniProtKB:P07900};
CC -!- ACTIVITY REGULATION: In the resting state, through the dimerization of
CC its C-terminal domain, HSP90 forms a homodimer which is defined as the
CC open conformation (By similarity). Upon ATP-binding, the N-terminal
CC domain undergoes significant conformational changes and comes in
CC contact to form an active closed conformation (By similarity). After
CC HSP90 finishes its chaperoning tasks of assisting the proper folding,
CC stabilization and activation of client proteins under the active state,
CC ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and
CC directs the protein back to the resting state (By similarity). Co-
CC chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase
CC activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes
CC HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin,
CC Ganetespib (STA-9090) and SNX-2112 (By similarity).
CC {ECO:0000250|UniProtKB:P07900, ECO:0000269|PubMed:29127155}.
CC -!- SUBUNIT: Homodimer (PubMed:8289821). Identified in NR3C1/GCR steroid
CC receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a
CC variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID,
CC PPP5C or STIP1 (PubMed:9195923, PubMed:11278753, PubMed:11751894).
CC Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to
CC recruit TCS2 to the complex (By similarity). The closed form interacts
CC (via the middle domain and TPR repeat-binding motif) with co-chaperone
CC TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (By
CC similarity). Interacts with TERT; the interaction, together with
CC PTGES3, is required for correct assembly and stabilization of the TERT
CC holoenzyme complex (By similarity). Interacts with CHORDC1 and DNAJC7
CC (By similarity). Interacts with STUB1 and UBE2N; may couple the
CC chaperone and ubiquitination systems (By similarity). Interacts (via
CC TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction
CC is direct and activates PPP5C phosphatase activity (By similarity).
CC Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8
CC (By similarity). Interacts with KSR1 (PubMed:10409742). Interacts with
CC co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1
CC ATPase activity (By similarity). May interact with NWD1 (By
CC similarity). Interacts with FNIP1 and FNIP2; the interaction inhibits
CC HSP90AA1 ATPase activity (By similarity). Interacts with co-chaperone
CC AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1
CC ATPase activity and results in the dissociation of TSC1 from HSP90AA1
CC (PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (By
CC similarity). Interacts with HSP70, STIP1 and PTGES3 (By similarity).
CC Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-
CC methyltransferase (By similarity). Interacts with SGTA (via TPR
CC repeats) (By similarity). Interacts with TTC1 (via TPR repeats) (By
CC similarity). Interacts with HSF1 in an ATP-dependent manner (By
CC similarity). Interacts with MET; the interaction suppresses MET kinase
CC activity (By similarity). Interacts with ERBB2 in an ATP-dependent
CC manner; the interaction suppresses ERBB2 kinase activity (By
CC similarity). Interacts with HIF1A, KEAP1 and RHOBTB2 (By similarity).
CC Interacts with HSF1; this interaction is decreased in a IER5-dependent
CC manner, promoting HSF1 accumulation in the nucleus, homotrimerization
CC and DNA-binding activities (By similarity). Interacts with STUB1 and
CC SMAD3 (By similarity). Interacts with HSP90AB1; interaction is
CC constitutive (By similarity). Interacts with HECTD1 (via N-terminus)
CC (PubMed:22431752). Interacts with NR3C1 (via domain NR LBD) and NR1D1
CC (via domain NR LBD) (PubMed:27686098). Interacts with NLPR12. Interacts
CC with PDCL3 (PubMed:27496612). Interacts with TOMM70; the interaction is
CC required for preprotein mitochondrial import. Interacts with TOMM70,
CC IRF3 and TBK1; the interactions are direct and mediate the association
CC of TOMM70 with IRF3 and TBK1 (By similarity). Forms a complex with ASL,
CC ASS1 and NOS2; the complex regulates cell-autonomous L-arginine
CC synthesis and citrulline recycling while channeling extracellular L-
CC arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P07900, ECO:0000269|PubMed:10409742,
CC ECO:0000269|PubMed:11278753, ECO:0000269|PubMed:11751894,
CC ECO:0000269|PubMed:22081021, ECO:0000269|PubMed:22431752,
CC ECO:0000269|PubMed:27496612, ECO:0000269|PubMed:27686098,
CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:8289821,
CC ECO:0000269|PubMed:9195923}.
CC -!- INTERACTION:
CC P07901; P31750: Akt1; NbExp=6; IntAct=EBI-78930, EBI-298707;
CC P07901; Q9R000: Itgb1bp2; NbExp=5; IntAct=EBI-78930, EBI-7922331;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22431752}. Cytoplasm
CC {ECO:0000269|PubMed:11751894, ECO:0000269|PubMed:22431752,
CC ECO:0000269|PubMed:27496612, ECO:0000269|PubMed:27686098}. Melanosome
CC {ECO:0000250|UniProtKB:P07900}. Cell membrane
CC {ECO:0000250|UniProtKB:P07900}. Mitochondrion
CC {ECO:0000250|UniProtKB:P07900}.
CC -!- DOMAIN: The TPR repeat-binding motif mediates interaction with TPR
CC repeat-containing proteins like the co-chaperone STUB1.
CC {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- PTM: S-nitrosylated; negatively regulates the ATPase activity and the
CC activation of eNOS by HSP90AA1. {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1.
CC Ubiquitination promotes translocation into the cytoplasm away from the
CC membrane and secretory pathways. {ECO:0000269|PubMed:22431752}.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}.
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DR EMBL; J04633; AAA53068.1; -; mRNA.
DR EMBL; M57673; AAA37867.1; -; Genomic_DNA.
DR EMBL; BC046614; AAH46614.1; -; mRNA.
DR EMBL; M36830; AAA37868.1; -; mRNA.
DR EMBL; X16857; CAA34748.1; -; mRNA.
DR CCDS; CCDS26172.1; -.
DR PIR; B32848; HHMS86.
DR RefSeq; NP_034610.1; NM_010480.5.
DR PDB; 5H22; X-ray; 1.50 A; A=10-224.
DR PDB; 7D1V; X-ray; 1.33 A; A=16-224.
DR PDB; 7D22; X-ray; 1.60 A; A=16-224.
DR PDB; 7D24; X-ray; 1.55 A; A=16-224.
DR PDB; 7D25; X-ray; 1.65 A; A=16-224.
DR PDB; 7D26; X-ray; 1.75 A; A=16-224.
DR PDBsum; 5H22; -.
DR PDBsum; 7D1V; -.
DR PDBsum; 7D22; -.
DR PDBsum; 7D24; -.
DR PDBsum; 7D25; -.
DR PDBsum; 7D26; -.
DR AlphaFoldDB; P07901; -.
DR BMRB; P07901; -.
DR SMR; P07901; -.
DR BioGRID; 200455; 84.
DR ComplexPortal; CPX-3289; HSP90A-CDC37 chaperone complex.
DR CORUM; P07901; -.
DR DIP; DIP-30975N; -.
DR ELM; P07901; -.
DR IntAct; P07901; 34.
DR MINT; P07901; -.
DR STRING; 10090.ENSMUSP00000091921; -.
DR BindingDB; P07901; -.
DR ChEMBL; CHEMBL4197; -.
DR CarbonylDB; P07901; -.
DR GlyConnect; 2367; 1 N-Linked glycan (1 site).
DR GlyGen; P07901; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; P07901; -.
DR MetOSite; P07901; -.
DR PhosphoSitePlus; P07901; -.
DR SwissPalm; P07901; -.
DR REPRODUCTION-2DPAGE; P07901; -.
DR CPTAC; non-CPTAC-3822; -.
DR EPD; P07901; -.
DR jPOST; P07901; -.
DR PaxDb; P07901; -.
DR PeptideAtlas; P07901; -.
DR PRIDE; P07901; -.
DR ProteomicsDB; 273386; -.
DR Antibodypedia; 3676; 1858 antibodies from 45 providers.
DR DNASU; 15519; -.
DR Ensembl; ENSMUST00000021698; ENSMUSP00000021698; ENSMUSG00000021270.
DR Ensembl; ENSMUST00000094361; ENSMUSP00000091921; ENSMUSG00000021270.
DR GeneID; 15519; -.
DR KEGG; mmu:15519; -.
DR UCSC; uc007pbq.2; mouse.
DR CTD; 3320; -.
DR MGI; MGI:96250; Hsp90aa1.
DR VEuPathDB; HostDB:ENSMUSG00000021270; -.
DR eggNOG; KOG0019; Eukaryota.
DR GeneTree; ENSGT01020000230401; -.
DR HOGENOM; CLU_006684_1_3_1; -.
DR InParanoid; P07901; -.
DR OMA; MRRMKEM; -.
DR OrthoDB; 924636at2759; -.
DR PhylomeDB; P07901; -.
DR TreeFam; TF300686; -.
DR Reactome; R-MMU-1227986; Signaling by ERBB2.
DR Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-MMU-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-203615; eNOS activation.
DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-3371511; HSF1 activation.
DR Reactome; R-MMU-3371568; Attenuation phase.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-MMU-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-MMU-8854518; AURKA Activation by TPX2.
DR Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-MMU-8939211; ESR-mediated signaling.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR Reactome; R-MMU-9652282; Drug-mediated inhibition of ERBB2 signaling.
DR BioGRID-ORCS; 15519; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Hsp90aa1; mouse.
DR PRO; PR:P07901; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P07901; protein.
DR Bgee; ENSMUSG00000021270; Expressed in primary oocyte and 136 other tissues.
DR ExpressionAtlas; P07901; baseline and differential.
DR Genevisible; P07901; MM.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0044295; C:axonal growth cone; IDA:ARUK-UCL.
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:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0044294; C:dendritic growth cone; IDA:ARUK-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IEA:Ensembl.
DR GO; GO:0097524; C:sperm plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0002135; F:CTP binding; IEA:Ensembl.
DR GO; GO:0032564; F:dATP binding; IEA:Ensembl.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0003729; F:mRNA binding; IEA:Ensembl.
DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; IDA:UniProtKB.
DR GO; GO:0044183; F:protein folding chaperone; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0051022; F:Rho GDP-dissociation inhibitor binding; IEA:Ensembl.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0017098; F:sulfonylurea receptor binding; IEA:Ensembl.
DR GO; GO:0048156; F:tau protein binding; ISO:MGI.
DR GO; GO:0030911; F:TPR domain binding; ISS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0002134; F:UTP binding; IEA:Ensembl.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:ARUK-UCL.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IMP:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; ISS:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:ARUK-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; ISO:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:ARUK-UCL.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:UniProtKB.
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:0045585; P:positive regulation of cytotoxic T cell differentiation; TAS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0032273; P:positive regulation of protein polymerization; ISO:MGI.
DR GO; GO:1902949; P:positive regulation of tau-protein kinase activity; ISO:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:0006457; P:protein folding; IMP:UniProtKB.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0042026; P:protein refolding; TAS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:ARUK-UCL.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0046677; P:response to antibiotic; ISS:AgBase.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; ISS:AgBase.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; ISS:AgBase.
DR GO; GO:0009651; P:response to salt stress; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; TAS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:1905323; P:telomerase holoenzyme complex assembly; ISO:MGI.
DR GO; GO:0007004; P:telomere maintenance via telomerase; ISO:MGI.
DR Gene3D; 1.20.120.790; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR HAMAP; MF_00505; HSP90; 1.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR037196; HSP90_C.
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; SSF110942; SSF110942; 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; ATP-binding; Cell membrane; Chaperone;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Membrane; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Stress response; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3458168,
FT ECO:0000269|PubMed:8289821"
FT CHAIN 2..733
FT /note="Heat shock protein HSP 90-alpha"
FT /id="PRO_0000062912"
FT REGION 9..236
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000269|PubMed:27686098"
FT REGION 225..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..617
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000269|PubMed:27686098"
FT REGION 285..733
FT /note="Interaction with FLCN and FNIP1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 285..621
FT /note="Interaction with FNIP2 and TSC1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 629..732
FT /note="Interaction with NR1D1"
FT /evidence="ECO:0000269|PubMed:27686098"
FT REGION 683..733
FT /note="Required for homodimerization"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 701..733
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 729..733
FT /note="Essential for interaction with SMYD3, TSC1 and
FT STIP1/HOP"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 730..733
FT /note="Essential for interaction with SGTA and TTC1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOTIF 724..733
FT /note="TPR repeat-binding"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT COMPBIAS 243..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 401
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 5
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:2507541"
FT MOD_RES 7
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:2507541"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:18630941, ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 314
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 444
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P82995"
FT MOD_RES 459
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 493
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 586
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 599
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT CONFLICT 7
FT /note="T -> A (in Ref. 6; AAA37868)"
FT /evidence="ECO:0000305"
FT CONFLICT 242..245
FT /note="Missing (in Ref. 6; AAA37868)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="R -> K (in Ref. 6; AAA37868)"
FT /evidence="ECO:0000305"
FT STRAND 17..21
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 24..35
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 43..63
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:7D1V"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 106..123
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 181..190
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 192..198
FT /evidence="ECO:0007829|PDB:7D1V"
FT HELIX 200..210
FT /evidence="ECO:0007829|PDB:7D1V"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:7D1V"
SQ SEQUENCE 733 AA; 84788 MW; D92B8FD38A463B4E CRC64;
MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR
YESLTDPSKL DSGKELHINL IPSKQDRTLT IVDTGIGMTK ADLINNLGTI AKSGTKAFME
ALQAGADISM IGQFGVGFYS AYLVAEKVTV ITKHNDDEQY AWESSAGGSF TVRTDTGEPM
GRGTKVILHL KEDQTEYLEE RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKEE
KEEEKEKEEK ESDDKPEIED VGSDEEEEEK KDGDKKKKKK IKEKYIDQEE LNKTKPIWTR
NPDDITNEEY GEFYKSLTND WEEHLAVKHF SVEGQLEFRA LLFVPRRAPF DLFENRKKKN
NIKLYVRRVF IMDNCEELIP EYLNFIRGVV DSEDLPLNIS REMLQQSKIL KVIRKNLVKK
CLELFTELAE DKENYKKFYE QFSKNIKLGI HEDSQNRKKL SELLRYYTSA SGDEMVSLKD
YCTRMKENQK HIYFITGETK DQVANSAFVE RLRKHGLEVI YMIEPIDEYC VQQLKEFEGK
TLVSVTKEGL ELPEDEEEKK KQEEKKTKFE NLCKIMKDIL EKKVEKVVVS NRLVTSPCCI
VTSTYGWTAN MERIMKAQAL RDNSTMGYMA AKKHLEINPD HSIIETLRQK AEADKNDKSV
KDLVILLYET ALLSSGFSLE DPQTHANRIY RMIKLGLGID EDDPTVDDTS AAVTEEMPPL
EGDDDTSRME EVD
