HS90A_RAT
ID HS90A_RAT Reviewed; 733 AA.
AC P82995; Q91XW0;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 166.
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;
GN Name=Hsp90aa1 {ECO:0000312|RGD:631409}; Synonyms=Hsp86, Hspca;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RA Li C.W., Chang M.T., Lai Y., Chang W.M., Lai Y.K.;
RT "Cloning of rat 86-kDa heat shock protein gene and promoter.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Lai Y.R., Chang M.D., Chang W.M., Su C.Y., Lai Y.K.;
RT "Cloning of full length cDNA of rat 86-kDa heat shock protein gene.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart, and Testis;
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 2-13.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=11732320; DOI=10.1007/bf01288360;
RA Langer T., Fasold H.;
RT "Isolation and quantification of the heat shock protein 90 alpha and beta
RT isoforms from rat liver.";
RL Protoplasma 218:54-56(2001).
RN [5]
RP PROTEIN SEQUENCE OF 154-173; 329-339 AND 347-356, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [6]
RP INTERACTION WITH SGTA.
RX PubMed=15708368; DOI=10.1016/j.abb.2004.12.020;
RA Liou S.T., Wang C.;
RT "Small glutamine-rich tetratricopeptide repeat-containing protein is
RT composed of three structural units with distinct functions.";
RL Arch. Biochem. Biophys. 435:253-263(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; SER-252; SER-263 AND
RP SER-454, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP INTERACTION WITH PDCL3.
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. Upon ATP-binding, the N-terminal domain undergoes
CC significant conformational changes and comes in contact to form an
CC active closed conformation. After HSP90 finishes its chaperoning tasks
CC of assisting the proper folding, stabilization and activation of client
CC proteins under the active state, ATP molecule is hydrolyzed to ADP
CC which then dissociates from HSP90 and directs the protein back to the
CC resting state. Co-chaperone TSC1 promotes ATP binding and inhibits
CC HSP90AA1 ATPase activity. Binding to phosphorylated AHSA1 promotes
CC HSP90AA1 ATPase activity. Inhibited by geldanamycin, Ganetespib (STA-
CC 9090) and SNX-2112. {ECO:0000250|UniProtKB:P07900}.
CC -!- SUBUNIT: Homodimer (By similarity). 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 (By similarity). Forms a complex containing HSP90AA1,
CC TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By
CC similarity). The closed form interacts (via the middle domain and TPR
CC repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (By
CC similarity). Interacts with TOM34 (By similarity). Interacts with TERT;
CC the interaction, together with PTGES3, is required for correct assembly
CC and stabilization of the TERT holoenzyme complex (By similarity).
CC Interacts with CHORDC1 and DNAJC7 (By similarity). Interacts with STUB1
CC and UBE2N; may couple the chaperone and ubiquitination systems (By
CC similarity). Interacts (via TPR repeat-binding motif) with PPP5C (via
CC TPR repeats); the interaction is direct and activates PPP5C phosphatase
CC activity (By similarity). Following LPS binding, may form a complex
CC with CXCR4, GDF5 and HSPA8 (By similarity). Interacts with KSR1 (By
CC similarity). Interacts with co-chaperone CDC37 (via C-terminus); the
CC interaction inhibits HSP90AA1 ATPase activity (By similarity). May
CC interact with NWD1 (By similarity). Interacts with FNIP1 and FNIP2; the
CC interaction inhibits HSP90AA1 ATPase activity (By similarity).
CC Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the
CC interaction activates HSP90AA1 ATPase activity and results in the
CC dissociation of TSC1 from HSP90AA1 (By similarity). Interacts with FLCN
CC in the presence of FNIP1 (By similarity). Interacts with HSP70, STIP1
CC and PTGES3 (By similarity). Interacts with SGTA (via TPR repeats)
CC (PubMed:15708368). Interacts with SMYD3; this interaction enhances
CC SMYD3 histone-lysine N-methyltransferase (By similarity). Interacts
CC with TTC1 (via TPR repeats) (By similarity). Interacts with HSF1 in an
CC ATP-dependent manner (By similarity). Interacts with MET; the
CC interaction suppresses MET kinase activity (By similarity). Interacts
CC with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2
CC kinase activity (By similarity). Interacts with HIF1A, KEAP1 and
CC RHOBTB2 (By similarity). Interacts with HSF1; this interaction is
CC decreased in a IER5-dependent manner, promoting HSF1 accumulation in
CC the nucleus, homotrimerization and DNA-binding activities. Interacts
CC with STUB1 and SMAD3 (By similarity). Interacts with HSP90AB1;
CC interaction is constitutive (By similarity). Interacts with HECTD1 (via
CC N-terminus) (By similarity). Interacts with NR3C1 (via domain NR LBD)
CC and NR1D1 (via domain NR LBD) (By similarity). Interacts with NLPR12.
CC Interacts with PDCL3 (PubMed:27496612). Interacts with TOMM70; the
CC interaction is required for preprotein mitochondrial import. Interacts
CC with TOMM70, IRF3 and TBK1; the interactions are direct and mediate the
CC association of TOMM70 with IRF3 and TBK1 (By similarity). Forms a
CC complex with ASL, ASS1 and NOS2; the complex regulates cell-autonomous
CC L-arginine synthesis and citrulline recycling while channeling
CC extracellular L-arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P07900, ECO:0000250|UniProtKB:P07901,
CC ECO:0000269|PubMed:15708368, ECO:0000269|PubMed:27496612}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P07901}. Cytoplasm
CC {ECO:0000250|UniProtKB:P07901}. 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:0000250|UniProtKB:P07900}.
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:0000250|UniProtKB:P07901}.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}.
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DR EMBL; AJ297736; CAC39453.1; -; Genomic_DNA.
DR EMBL; AJ428213; CAD21648.1; -; mRNA.
DR EMBL; BC072489; AAH72489.1; -; mRNA.
DR EMBL; BC085120; AAH85120.1; -; mRNA.
DR RefSeq; NP_786937.1; NM_175761.2.
DR RefSeq; XP_008763191.1; XM_008764969.2.
DR AlphaFoldDB; P82995; -.
DR SMR; P82995; -.
DR BioGRID; 256205; 28.
DR CORUM; P82995; -.
DR IntAct; P82995; 7.
DR MINT; P82995; -.
DR STRING; 10116.ENSRNOP00000009556; -.
DR CarbonylDB; P82995; -.
DR iPTMnet; P82995; -.
DR jPOST; P82995; -.
DR PaxDb; P82995; -.
DR PRIDE; P82995; -.
DR Ensembl; ENSRNOT00000086310; ENSRNOP00000075715; ENSRNOG00000059714.
DR GeneID; 299331; -.
DR KEGG; rno:299331; -.
DR UCSC; RGD:631409; rat.
DR CTD; 3320; -.
DR RGD; 631409; Hsp90aa1.
DR eggNOG; KOG0019; Eukaryota.
DR GeneTree; ENSGT01020000230401; -.
DR HOGENOM; CLU_006684_1_3_1; -.
DR InParanoid; P82995; -.
DR OMA; MRRMKEM; -.
DR OrthoDB; 924636at2759; -.
DR PhylomeDB; P82995; -.
DR TreeFam; TF300686; -.
DR Reactome; R-RNO-1227986; Signaling by ERBB2.
DR Reactome; R-RNO-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-RNO-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-203615; eNOS activation.
DR Reactome; R-RNO-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-RNO-3371511; HSF1 activation.
DR Reactome; R-RNO-3371568; Attenuation phase.
DR Reactome; R-RNO-3371571; HSF1-dependent transactivation.
DR Reactome; R-RNO-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-RNO-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-RNO-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-RNO-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-RNO-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-RNO-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-RNO-5675482; Regulation of necroptotic cell death.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-RNO-8854518; AURKA Activation by TPX2.
DR Reactome; R-RNO-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-RNO-8939211; ESR-mediated signaling.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR Reactome; R-RNO-9652282; Drug-mediated inhibition of ERBB2 signaling.
DR PRO; PR:P82995; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000007219; Expressed in cerebellum and 9 other tissues.
DR Genevisible; P82995; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0044295; C:axonal growth cone; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0044294; C:dendritic growth cone; ISO:RGD.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; NAS:ParkinsonsUK-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; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0036126; C:sperm flagellum; IDA:RGD.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IDA:RGD.
DR GO; GO:0097524; C:sperm plasma membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:RGD.
DR GO; GO:0002135; F:CTP binding; IDA:RGD.
DR GO; GO:0032564; F:dATP binding; IDA:RGD.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0051020; F:GTPase binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; IDA:RGD.
DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; ISS:UniProtKB.
DR GO; GO:0140597; F:protein carrier chaperone; NAS:ParkinsonsUK-UCL.
DR GO; GO:0044183; F:protein folding chaperone; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0051022; F:Rho GDP-dissociation inhibitor binding; IDA:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0017098; F:sulfonylurea receptor binding; IPI:RGD.
DR GO; GO:0048156; F:tau protein binding; IPI:RGD.
DR GO; GO:0030911; F:TPR domain binding; ISS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0002134; F:UTP binding; IDA:RGD.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; ISO:RGD.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEP:RGD.
DR GO; GO:0034605; P:cellular response to heat; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISS:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISO:RGD.
DR GO; GO:0061684; P:chaperone-mediated autophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; ISO:RGD.
DR GO; GO:0030010; P:establishment of cell polarity; ISO:RGD.
DR GO; GO:0001764; P:neuron migration; IMP:RGD.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEP:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:RGD.
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; IMP:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0032273; P:positive regulation of protein polymerization; ISO:RGD.
DR GO; GO:1902949; P:positive regulation of tau-protein kinase activity; ISO:RGD.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:RGD.
DR GO; GO:0006457; P:protein folding; ISO:RGD.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0061635; P:regulation of protein complex stability; NAS:ParkinsonsUK-UCL.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0046677; P:response to antibiotic; ISS:AgBase.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0009409; P:response to cold; ISS:AgBase.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0003009; P:skeletal muscle contraction; IEP:RGD.
DR GO; GO:1905323; P:telomerase holoenzyme complex assembly; ISO:RGD.
DR GO; GO:0007004; P:telomere maintenance via telomerase; ISO:RGD.
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 Acetylation; ATP-binding; Cell membrane; Chaperone; Cytoplasm;
KW 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:11732320"
FT CHAIN 2..733
FT /note="Heat shock protein HSP 90-alpha"
FT /id="PRO_0000062915"
FT REGION 9..236
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:P07901"
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:0000250|UniProtKB:P07901"
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:0000250|UniProtKB:P07901"
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:0000250|UniProtKB:P07900"
FT MOD_RES 7
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 314
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 444
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 459
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 493
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
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"
SQ SEQUENCE 733 AA; 84815 MW; DF2C8383A6581D07 CRC64;
MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR
YESLTDPSKL DSGKELHINL IPNKQDRTLT 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
