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Protein

Heat shock protein HSP 90-alpha

Gene

HSP90AA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385).3 Publications6 Publications

Enzyme regulationi

In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.1 Publication

Kineticsi

  1. KM=300 µM for ATP1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei51ATP1
    Binding sitei93ATP1
    Binding sitei112ATPBy similarity1
    Binding sitei138ATP; via amide nitrogen1
    Binding sitei400ATPBy similarity1

    GO - Molecular functioni

    • ATPase activity Source: UniProtKB
    • ATP binding Source: UniProtKB
    • disordered domain specific binding Source: CAFA
    • DNA polymerase binding Source: BHF-UCL
    • GTPase binding Source: UniProtKB
    • histone deacetylase binding Source: BHF-UCL
    • identical protein binding Source: IntAct
    • MHC class II protein complex binding Source: UniProtKB
    • nitric-oxide synthase regulator activity Source: UniProtKB
    • nucleotide binding Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • protein tyrosine kinase activity Source: Reactome
    • protein tyrosine kinase binding Source: UniProtKB
    • RNA binding Source: UniProtKB
    • TPR domain binding Source: UniProtKB
    • unfolded protein binding Source: InterPro

    GO - Biological processi

    • chaperone-mediated autophagy Source: ParkinsonsUK-UCL
    • chaperone-mediated protein complex assembly Source: BHF-UCL
    • ciliary basal body docking Source: Reactome
    • ERBB2 signaling pathway Source: Reactome
    • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    • G2/M transition of mitotic cell cycle Source: Reactome
    • mitochondrial transport Source: UniProtKB
    • neutrophil degranulation Source: Reactome
    • positive regulation of nitric oxide biosynthetic process Source: UniProtKB
    • positive regulation of telomerase activity Source: BHF-UCL
    • protein import into mitochondrial outer membrane Source: BHF-UCL
    • protein refolding Source: UniProtKB
    • protein stabilization Source: UniProtKB
    • protein unfolding Source: ParkinsonsUK-UCL
    • receptor-mediated endocytosis Source: Reactome
    • regulation of cellular response to heat Source: Reactome
    • regulation of nitric-oxide synthase activity Source: Reactome
    • regulation of protein complex assembly Source: ParkinsonsUK-UCL
    • regulation of protein ubiquitination Source: BHF-UCL
    • response to antibiotic Source: AgBase
    • response to cold Source: AgBase
    • response to heat Source: AgBase
    • response to unfolded protein Source: UniProtKB
    • signal transduction Source: UniProtKB
    • telomerase holoenzyme complex assembly Source: BHF-UCL
    • telomere maintenance via telomerase Source: BHF-UCL
    • vascular endothelial growth factor receptor signaling pathway Source: Reactome

    Keywordsi

    Molecular functionChaperone
    Biological processStress response
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-HSA-1227986. Signaling by ERBB2.
    R-HSA-1236382. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
    R-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    R-HSA-192905. vRNP Assembly.
    R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
    R-HSA-203615. eNOS activation.
    R-HSA-2565942. Regulation of PLK1 Activity at G2/M Transition.
    R-HSA-3000484. Scavenging by Class F Receptors.
    R-HSA-3371497. HSP90 chaperone cycle for steroid hormone receptors (SHR).
    R-HSA-3371511. HSF1 activation.
    R-HSA-3371568. Attenuation phase.
    R-HSA-3371571. HSF1-dependent transactivation.
    R-HSA-380259. Loss of Nlp from mitotic centrosomes.
    R-HSA-380270. Recruitment of mitotic centrosome proteins and complexes.
    R-HSA-380284. Loss of proteins required for interphase microtubule organization from the centrosome.
    R-HSA-3928663. EPHA-mediated growth cone collapse.
    R-HSA-399954. Sema3A PAK dependent Axon repulsion.
    R-HSA-4420097. VEGFA-VEGFR2 Pathway.
    R-HSA-5218920. VEGFR2 mediated vascular permeability.
    R-HSA-5336415. Uptake and function of diphtheria toxin.
    R-HSA-5601884. PIWI-interacting RNA (piRNA) biogenesis.
    R-HSA-5620912. Anchoring of the basal body to the plasma membrane.
    R-HSA-5637810. Constitutive Signaling by EGFRvIII.
    R-HSA-6785807. Interleukin-4 and 13 signaling.
    R-HSA-6798695. Neutrophil degranulation.
    R-HSA-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
    R-HSA-8854518. AURKA Activation by TPX2.
    R-HSA-8863795. Downregulation of ERBB2 signaling.
    SIGNORiP07900.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Heat shock protein HSP 90-alpha
    Alternative name(s):
    Heat shock 86 kDa
    Short name:
    HSP 86
    Short name:
    HSP86
    Lipopolysaccharide-associated protein 2
    Short name:
    LAP-2
    Short name:
    LPS-associated protein 2
    Renal carcinoma antigen NY-REN-38
    Gene namesi
    Name:HSP90AA1
    Synonyms:HSP90A, HSPC1, HSPCA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:5253. HSP90AA1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: CAFA
    • cytosol Source: Reactome
    • endocytic vesicle lumen Source: Reactome
    • extracellular exosome Source: UniProtKB
    • extracellular region Source: Reactome
    • ficolin-1-rich granule lumen Source: Reactome
    • lysosomal lumen Source: ParkinsonsUK-UCL
    • melanosome Source: UniProtKB-SubCell
    • membrane Source: UniProtKB
    • myelin sheath Source: Ensembl
    • nucleoplasm Source: Reactome
    • nucleus Source: UniProtKB
    • plasma membrane Source: Reactome
    • protein complex Source: UniProtKB
    • ruffle membrane Source: Ensembl
    • secretory granule lumen Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi47E → A: Strong ATP-binding. Strong interaction with HSF1, HIF1A, ERBB2, MET, KEAP1 and RHOBTB2. 1 Publication1
    Mutagenesisi93D → A: Impaired ATP-binding. Strong interaction with HIF1A, MET, KEAP1 and RHOBTB2. Loss of interaction with HSF1 and ERBB2. 1 Publication1
    Mutagenesisi97G → D: Abolishes ATPase activity. 1 Publication1
    Mutagenesisi598C → A, N or D: Reduces ATPase activity and client protein activation. 2 Publications1
    Mutagenesisi598C → S: Loss of S-nitrosylation. 2 Publications1

    Organism-specific databases

    DisGeNETi3320.
    OpenTargetsiENSG00000080824.
    PharmGKBiPA29519.

    Chemistry databases

    ChEMBLiCHEMBL3880.
    DrugBankiDB07317. (3E)-3-[(phenylamino)methylidene]dihydrofuran-2(3H)-one.
    DB03080. 17-Dmag.
    DB08786. 4-(2-methoxyethoxy)-6-methylpyrimidin-2-amine.
    DB03809. 9-Butyl-8-(3-Methoxybenzyl)-9h-Purin-6-Amine.
    DB03899. 9-Butyl-8-(4-Methoxybenzyl)-9h-Purin-6-Amine.
    DB05134. CNF1010.
    DB02424. Geldanamycin.
    DB07325. N-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)METHYL]-3-{[(E)-(2-OXODIHYDROFURAN-3(2H)-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE.
    DB00716. Nedocromil.
    DB00615. Rifabutin.
    DB06070. SNX-5422.
    GuidetoPHARMACOLOGYi2905.

    Polymorphism and mutation databases

    BioMutaiHSP90AA1.
    DMDMi92090606.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00000629112 – 732Heat shock protein HSP 90-alphaAdd BLAST731

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei5Phosphothreonine; by PRKDC1 Publication1
    Modified residuei7Phosphothreonine; by PRKDC1 Publication1
    Modified residuei58N6-acetyllysineBy similarity1
    Modified residuei84N6-acetyllysineBy similarity1
    Modified residuei231PhosphoserineCombined sources1
    Modified residuei252PhosphoserineCombined sources1
    Modified residuei263PhosphoserineCombined sources1
    Modified residuei313PhosphotyrosineBy similarity1
    Modified residuei399Phosphoserine1 Publication1
    Modified residuei443N6-acetyllysineCombined sources1
    Modified residuei453PhosphoserineBy similarity1
    Modified residuei458N6-acetyllysineCombined sources1
    Modified residuei476PhosphoserineCombined sources1
    Modified residuei489N6-acetyllysineCombined sources1
    Modified residuei492PhosphotyrosineBy similarity1
    Modified residuei585N6-acetyllysineCombined sources1
    Modified residuei598S-nitrosocysteine1 Publication1
    Modified residuei641PhosphoserineCombined sources1

    Post-translational modificationi

    ISGylated.1 Publication
    S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein, S-nitrosylation, Ubl conjugation

    Proteomic databases

    EPDiP07900.
    MaxQBiP07900.
    PaxDbiP07900.
    PeptideAtlasiP07900.
    PRIDEiP07900.
    TopDownProteomicsiP07900-1. [P07900-1]

    2D gel databases

    OGPiP07900.
    REPRODUCTION-2DPAGEiIPI00784295.

    PTM databases

    iPTMnetiP07900.
    PhosphoSitePlusiP07900.
    SwissPalmiP07900.

    Miscellaneous databases

    PMAP-CutDBiP07900.

    Expressioni

    Gene expression databases

    BgeeiENSG00000080824.
    CleanExiHS_HSP90AA1.
    ExpressionAtlasiP07900. baseline and differential.
    GenevisibleiP07900. HS.

    Organism-specific databases

    HPAiCAB002058.

    Interactioni

    Subunit structurei

    Homodimer (PubMed:7588731, PubMed:8289821, PubMed:18400751). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:15383005, PubMed:9195923). Interacts with TOM34 (PubMed:9660753). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (PubMed:16307917, PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (PubMed:15383005, PubMed:15577939, PubMed:16531226, PubMed:27353360). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (PubMed:23569206, PubMed:27353360). May interact with NWD1 (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). Interacts with AHSA1; the interaction activates HSP90AA1 ATPase activity (PubMed:12604615, PubMed:27353360). Interacts with FLCN in the presence of FNIP1. Interacts with HSP70, STIP1 and PTGES3 (PubMed:27353360). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:15235609, PubMed:25738358). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with HSF1 in an ATP-dependent manner (PubMed:11583998. PubMed:26517842). Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2 (PubMed:26517842). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (PubMed:26754925). Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with HSP90AB1; interaction is constitutive (PubMed:20353823).28 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • disordered domain specific binding Source: CAFA
    • DNA polymerase binding Source: BHF-UCL
    • GTPase binding Source: UniProtKB
    • histone deacetylase binding Source: BHF-UCL
    • identical protein binding Source: IntAct
    • MHC class II protein complex binding Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • protein tyrosine kinase binding Source: UniProtKB
    • TPR domain binding Source: UniProtKB
    • unfolded protein binding Source: InterPro

    Protein-protein interaction databases

    BioGridi109552. 811 interactors.
    DIPiDIP-27595N.
    IntActiP07900. 227 interactors.
    MINTiMINT-132070.
    STRINGi9606.ENSP00000335153.

    Chemistry databases

    BindingDBiP07900.

    Structurei

    Secondary structure

    1732
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi18 – 21Combined sources4
    Helixi24 – 35Combined sources12
    Helixi43 – 63Combined sources21
    Helixi67 – 70Combined sources4
    Beta strandi78 – 83Combined sources6
    Turni84 – 87Combined sources4
    Beta strandi88 – 93Combined sources6
    Helixi100 – 104Combined sources5
    Helixi106 – 108Combined sources3
    Helixi111 – 123Combined sources13
    Helixi128 – 134Combined sources7
    Helixi137 – 143Combined sources7
    Beta strandi145 – 153Combined sources9
    Beta strandi155 – 157Combined sources3
    Beta strandi159 – 164Combined sources6
    Beta strandi169 – 174Combined sources6
    Beta strandi181 – 190Combined sources10
    Helixi192 – 198Combined sources7
    Helixi200 – 210Combined sources11
    Beta strandi212 – 216Combined sources5
    Beta strandi218 – 220Combined sources3
    Turni221 – 224Combined sources4
    Beta strandi225 – 227Combined sources3
    Helixi228 – 230Combined sources3
    Helixi296 – 298Combined sources3
    Helixi306 – 317Combined sources12
    Beta strandi324 – 331Combined sources8
    Beta strandi333 – 335Combined sources3
    Beta strandi337 – 343Combined sources7
    Beta strandi361 – 365Combined sources5
    Beta strandi368 – 372Combined sources5
    Helixi380 – 382Combined sources3
    Beta strandi386 – 392Combined sources7
    Helixi408 – 427Combined sources20
    Helixi431 – 451Combined sources21
    Helixi453 – 455Combined sources3
    Helixi456 – 460Combined sources5
    Beta strandi464 – 467Combined sources4
    Turni468 – 472Combined sources5
    Helixi477 – 482Combined sources6
    Beta strandi490 – 495Combined sources6
    Helixi499 – 503Combined sources5
    Helixi506 – 508Combined sources3
    Helixi509 – 514Combined sources6
    Beta strandi518 – 521Combined sources4
    Helixi525 – 529Combined sources5
    Turni530 – 532Combined sources3
    Beta strandi539 – 543Combined sources5
    Helixi555 – 567Combined sources13
    Helixi569 – 578Combined sources10
    Helixi580 – 582Combined sources3
    Beta strandi584 – 588Combined sources5
    Beta strandi593 – 601Combined sources9
    Beta strandi603 – 605Combined sources3
    Helixi608 – 613Combined sources6
    Beta strandi632 – 636Combined sources5
    Helixi641 – 652Combined sources12
    Helixi657 – 673Combined sources17
    Helixi681 – 694Combined sources14
    Beta strandi728 – 730Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1BYQX-ray1.50A9-236[»]
    1OSFX-ray1.75A9-223[»]
    1UY6X-ray1.90A2-236[»]
    1UY7X-ray1.90A2-236[»]
    1UY8X-ray1.98A2-236[»]
    1UY9X-ray2.00A2-236[»]
    1UYCX-ray2.00A2-236[»]
    1UYDX-ray2.20A2-236[»]
    1UYEX-ray2.00A2-236[»]
    1UYFX-ray2.00A2-236[»]
    1UYGX-ray2.00A2-236[»]
    1UYHX-ray2.20A2-236[»]
    1UYIX-ray2.20A2-236[»]
    1UYKX-ray2.20A2-236[»]
    1UYLX-ray1.40A2-236[»]
    1YC1X-ray1.70A9-236[»]
    1YC3X-ray2.12A9-236[»]
    1YC4X-ray1.81A9-236[»]
    1YERX-ray1.65A9-236[»]
    1YESX-ray2.20A9-236[»]
    1YETX-ray1.90A9-236[»]
    2BSMX-ray2.05A2-236[»]
    2BT0X-ray1.90A/B2-236[»]
    2BUGNMR-B728-732[»]
    2BYHX-ray1.90A11-236[»]
    2BYIX-ray1.60A11-236[»]
    2BZ5X-ray1.90A/B2-236[»]
    2C2LX-ray3.30E/F/G/H724-732[»]
    2CCSX-ray1.79A1-236[»]
    2CCTX-ray2.30A1-236[»]
    2CCUX-ray2.70A1-236[»]
    2FWYX-ray2.10A1-236[»]
    2FWZX-ray2.10A1-236[»]
    2H55X-ray2.00A1-236[»]
    2JJCX-ray1.95A9-223[»]
    2K5BNMR-A14-223[»]
    2QF6X-ray3.10A/B/C/D17-223[»]
    2QFOX-ray1.68A/B17-223[»]
    2QG0X-ray1.85A/B17-223[»]
    2QG2X-ray1.80A17-223[»]
    2UWDX-ray1.90A2-236[»]
    2VCIX-ray2.00A1-236[»]
    2VCJX-ray2.50A1-236[»]
    2WI1X-ray2.30A1-236[»]
    2WI2X-ray2.09A/B1-236[»]
    2WI3X-ray1.90A1-236[»]
    2WI4X-ray2.40A1-236[»]
    2WI5X-ray2.10A1-236[»]
    2WI6X-ray2.18A1-236[»]
    2WI7X-ray2.50A1-236[»]
    2XABX-ray1.90A/B9-236[»]
    2XDKX-ray1.97A9-236[»]
    2XDLX-ray1.98A9-236[»]
    2XDSX-ray1.97A9-236[»]
    2XDUX-ray1.74A14-224[»]
    2XDXX-ray2.42A9-236[»]
    2XHRX-ray2.20A9-236[»]
    2XHTX-ray2.27A9-236[»]
    2XHXX-ray2.80A9-236[»]
    2XJGX-ray2.25A9-236[»]
    2XJJX-ray1.90A/B9-236[»]
    2XJXX-ray1.66A9-236[»]
    2XK2X-ray1.95A9-236[»]
    2YE2X-ray1.90A9-236[»]
    2YE3X-ray1.95A9-236[»]
    2YE4X-ray2.30A9-236[»]
    2YE5X-ray1.73A9-236[»]
    2YE6X-ray2.56A9-236[»]
    2YE7X-ray2.20A9-236[»]
    2YE8X-ray2.30A9-236[»]
    2YE9X-ray2.20A9-236[»]
    2YEAX-ray1.73A9-236[»]
    2YEBX-ray2.40A9-236[»]
    2YECX-ray2.10A9-236[»]
    2YEDX-ray2.10A9-236[»]
    2YEEX-ray2.30A9-236[»]
    2YEFX-ray1.55A9-236[»]
    2YEGX-ray2.50A/B9-236[»]
    2YEHX-ray2.10A9-236[»]
    2YEIX-ray2.20A9-236[»]
    2YEJX-ray2.20A9-236[»]
    2YI0X-ray1.60A1-229[»]
    2YI5X-ray2.50A1-229[»]
    2YI6X-ray1.80A1-229[»]
    2YI7X-ray1.40A1-229[»]
    2YJWX-ray1.61A18-223[»]
    2YJXX-ray1.83A18-223[»]
    2YK2X-ray1.74A18-223[»]
    2YK9X-ray1.32A18-223[»]
    2YKBX-ray1.93A18-223[»]
    2YKCX-ray1.67A18-223[»]
    2YKEX-ray1.43A18-223[»]
    2YKIX-ray1.67A18-223[»]
    2YKJX-ray1.46A18-223[»]
    3B24X-ray1.70A/B9-236[»]
    3B25X-ray1.75A9-236[»]
    3B26X-ray2.10A/B9-236[»]
    3B27X-ray1.50A9-236[»]
    3B28X-ray1.35A/B9-236[»]
    3BM9X-ray1.60A14-236[»]
    3BMYX-ray1.60A14-236[»]
    3D0BX-ray1.74A1-232[»]
    3EKOX-ray1.55A/B9-225[»]
    3EKRX-ray2.00A/B9-225[»]
    3FT5X-ray1.90A9-236[»]
    3FT8X-ray2.00A9-236[»]
    3HEKX-ray1.95A/B9-225[»]
    3HHUX-ray1.59A/B1-224[»]
    3HYYX-ray1.90A9-236[»]
    3HYZX-ray2.30A/B9-236[»]
    3HZ1X-ray2.30A9-236[»]
    3HZ5X-ray1.90A9-236[»]
    3INWX-ray1.95A10-236[»]
    3INXX-ray1.75A10-236[»]
    3K97X-ray1.95A9-236[»]
    3K98X-ray2.40A/B9-225[»]
    3K99X-ray2.10A/B/C/D9-225[»]
    3MNRX-ray1.90P1-232[»]
    3O0IX-ray1.47A1-236[»]
    3OW6X-ray1.80A17-223[»]
    3OWBX-ray2.05A17-223[»]
    3OWDX-ray1.63A17-223[»]
    3Q6MX-ray3.00A/B/C293-732[»]
    3Q6NX-ray3.05A/B/C/D/E/F293-732[»]
    3QDDX-ray1.79A1-236[»]
    3QTFX-ray1.57A14-236[»]
    3R4MX-ray1.70A9-236[»]
    3R4NX-ray2.00A/B9-225[»]
    3R4OX-ray2.65A/B9-225[»]
    3R4PX-ray1.70A/B9-225[»]
    3R91X-ray1.58A14-236[»]
    3R92X-ray1.58A14-236[»]
    3RKZX-ray1.57A14-236[»]
    3RLPX-ray1.70A/B9-225[»]
    3RLQX-ray1.90A/B9-225[»]
    3RLRX-ray1.70A/B9-225[»]
    3T0HX-ray1.20A9-236[»]
    3T0ZX-ray2.19A9-236[»]
    3T10X-ray1.24A9-236[»]
    3T1KX-ray1.50A/B9-236[»]
    3T2SX-ray1.50A/B9-236[»]
    3TUHX-ray1.80A/B16-224[»]
    3VHAX-ray1.39A9-236[»]
    3VHCX-ray1.41A9-236[»]
    3VHDX-ray1.52A/B9-236[»]
    3WHAX-ray1.30A/B9-236[»]
    3WQ9X-ray1.80A1-236[»]
    4AIFX-ray2.01D/E726-732[»]
    4AWOX-ray1.70A/B9-236[»]
    4AWPX-ray1.82A/B9-236[»]
    4AWQX-ray1.60A/B9-236[»]
    4B7PX-ray1.70A9-236[»]
    4BQGX-ray1.90A9-236[»]
    4BQJX-ray2.00A9-236[»]
    4CGQX-ray2.00Q726-732[»]
    4CGUX-ray2.11C726-732[»]
    4CGVX-ray2.54E/F726-732[»]
    4CGWX-ray3.00C/D726-732[»]
    4CWFX-ray2.00A9-236[»]
    4CWNX-ray1.80A9-236[»]
    4CWOX-ray2.31A9-236[»]
    4CWPX-ray1.95A9-236[»]
    4CWQX-ray2.00A9-236[»]
    4CWRX-ray2.00A9-236[»]
    4CWSX-ray2.30A9-236[»]
    4CWTX-ray1.90A9-236[»]
    4EEHX-ray1.60A9-236[»]
    4EFTX-ray2.12A9-236[»]
    4EFUX-ray2.00A9-236[»]
    4EGHX-ray1.60A9-236[»]
    4EGIX-ray1.79A9-236[»]
    4EGKX-ray1.69A9-236[»]
    4FCPX-ray2.00A/B1-236[»]
    4FCQX-ray2.15A1-236[»]
    4FCRX-ray1.70A1-236[»]
    4HY6X-ray1.65A9-236[»]
    4JQLX-ray1.72A9-236[»]
    4L8ZX-ray1.70A9-236[»]
    4L90X-ray2.00A9-236[»]
    4L91X-ray1.75A9-236[»]
    4L93X-ray1.84A/B9-236[»]
    4L94X-ray1.65A9-236[»]
    4LWEX-ray1.50A17-224[»]
    4LWFX-ray1.75A17-224[»]
    4LWGX-ray1.60A17-224[»]
    4LWHX-ray1.70A16-224[»]
    4LWIX-ray1.70A17-224[»]
    4NH7X-ray2.00A/B9-236[»]
    4NH8X-ray1.65A9-236[»]
    4O04X-ray1.82A9-236[»]
    4O05X-ray1.79A9-236[»]
    4O07X-ray1.86A9-236[»]
    4O09X-ray1.96A9-236[»]
    4O0BX-ray1.93A9-236[»]
    4R3MX-ray1.80A16-224[»]
    4U93X-ray1.55A1-236[»]
    4W7TX-ray1.80A1-236[»]
    4XIPX-ray1.70A9-236[»]
    4XIQX-ray1.84A9-236[»]
    4XIRX-ray1.70A9-236[»]
    4XITX-ray1.86A9-236[»]
    4YKQX-ray1.91A2-236[»]
    4YKRX-ray1.61A2-236[»]
    4YKTX-ray1.85A2-236[»]
    4YKUX-ray1.70A2-236[»]
    4YKWX-ray1.85A/B2-236[»]
    4YKXX-ray1.80A2-236[»]
    4YKYX-ray1.78A2-236[»]
    4YKZX-ray1.85A2-236[»]
    5CF0X-ray1.80A9-236[»]
    5FNCX-ray2.20A1-236[»]
    5FNDX-ray2.00A1-236[»]
    5FNFX-ray2.10A1-236[»]
    5GGZX-ray2.02A/B/C/D16-225[»]
    5M4EX-ray1.90A9-236[»]
    5M4HX-ray2.00A9-236[»]
    ProteinModelPortaliP07900.
    SMRiP07900.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP07900.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni284 – 732Interaction with FLCN and FNIP11 PublicationAdd BLAST449
    Regioni284 – 620Interaction with FNIP21 PublicationAdd BLAST337
    Regioni682 – 732Required for homodimerization1 PublicationAdd BLAST51
    Regioni728 – 732Essential for interaction with SMYD31 Publication5
    Regioni729 – 732Essential for interaction with SGTA and TTC11 Publication4

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi723 – 732TPR repeat-binding1 Publication10

    Domaini

    The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.1 Publication

    Sequence similaritiesi

    Belongs to the heat shock protein 90 family.Curated

    Phylogenomic databases

    eggNOGiKOG0019. Eukaryota.
    KOG0020. Eukaryota.
    COG0326. LUCA.
    GeneTreeiENSGT00840000129758.
    HOVERGENiHBG007374.
    InParanoidiP07900.
    KOiK04079.
    OMAiYESFGKN.
    OrthoDBiEOG091G0270.
    PhylomeDBiP07900.
    TreeFamiTF300686.

    Family and domain databases

    Gene3Di3.30.565.10. 1 hit.
    HAMAPiMF_00505. HSP90. 1 hit.
    InterProiView protein in InterPro
    IPR003594. HATPase_C.
    IPR019805. Heat_shock_protein_90_CS.
    IPR001404. Hsp90_fam.
    IPR020575. Hsp90_N.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    PANTHERiPTHR11528. PTHR11528. 1 hit.
    PfamiView protein in Pfam
    PF02518. HATPase_c. 1 hit.
    PF00183. HSP90. 1 hit.
    PIRSFiPIRSF002583. Hsp90. 1 hit.
    PRINTSiPR00775. HEATSHOCK90.
    SMARTiView protein in SMART
    SM00387. HATPase_c. 1 hit.
    SUPFAMiSSF54211. SSF54211. 1 hit.
    SSF55874. SSF55874. 1 hit.
    PROSITEiView protein in PROSITE
    PS00298. HSP90. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P07900-1) [UniParc]FASTAAdd to basket
    Also known as: HSP90AA1-1, HSP90-alpha 2

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS
    60 70 80 90 100
    NSSDALDKIR YESLTDPSKL DSGKELHINL IPNKQDRTLT IVDTGIGMTK
    110 120 130 140 150
    ADLINNLGTI AKSGTKAFME ALQAGADISM IGQFGVGFYS AYLVAEKVTV
    160 170 180 190 200
    ITKHNDDEQY AWESSAGGSF TVRTDTGEPM GRGTKVILHL KEDQTEYLEE
    210 220 230 240 250
    RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKED KEEEKEKEEK
    260 270 280 290 300
    ESEDKPEIED VGSDEEEEKK DGDKKKKKKI KEKYIDQEEL NKTKPIWTRN
    310 320 330 340 350
    PDDITNEEYG EFYKSLTNDW EDHLAVKHFS VEGQLEFRAL LFVPRRAPFD
    360 370 380 390 400
    LFENRKKKNN IKLYVRRVFI MDNCEELIPE YLNFIRGVVD SEDLPLNISR
    410 420 430 440 450
    EMLQQSKILK VIRKNLVKKC LELFTELAED KENYKKFYEQ FSKNIKLGIH
    460 470 480 490 500
    EDSQNRKKLS ELLRYYTSAS GDEMVSLKDY CTRMKENQKH IYYITGETKD
    510 520 530 540 550
    QVANSAFVER LRKHGLEVIY MIEPIDEYCV QQLKEFEGKT LVSVTKEGLE
    560 570 580 590 600
    LPEDEEEKKK QEEKKTKFEN LCKIMKDILE KKVEKVVVSN RLVTSPCCIV
    610 620 630 640 650
    TSTYGWTANM ERIMKAQALR DNSTMGYMAA KKHLEINPDH SIIETLRQKA
    660 670 680 690 700
    EADKNDKSVK DLVILLYETA LLSSGFSLED PQTHANRIYR MIKLGLGIDE
    710 720 730
    DDPTADDTSA AVTEEMPPLE GDDDTSRMEE VD
    Length:732
    Mass (Da):84,660
    Last modified:January 23, 2007 - v5
    Checksum:i969F65FCC0BC86FD
    GO
    Isoform 2 (identifier: P07900-2) [UniParc]FASTAAdd to basket
    Also known as: HSP90AA1-2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MPPCSGGDGS...QPFILLRLLM

    Show »
    Length:854
    Mass (Da):98,161
    Checksum:i404BD8CAD5E68DB0
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti63S → T in CAA33259 (PubMed:2780322).Curated1
    Sequence conflicti74K → R in CAI64495 (PubMed:16269234).Curated1
    Sequence conflicti74K → R in BAG51711 (PubMed:14702039).Curated1
    Sequence conflicti86D → G in CAI64495 (PubMed:16269234).Curated1
    Sequence conflicti86D → G in BAG51711 (PubMed:14702039).Curated1
    Sequence conflicti162W → D AA sequence (PubMed:10409742).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Isoform 2 (identifier: P07900-2)
    Natural varianti71M → L. Corresponds to variant dbSNP:rs8005905Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0266041M → MPPCSGGDGSTPPGPSLRDR DCPAQSAEYPRDRLDPRPGS PSEASSPPFLRSRAPVNWYQ EKAQVFLWHLMVSGSTTLLC LWKQPFHVSAFPVTASLAFR QSQGAGQHLYKDLQPFILLR LLM in isoform 2. 2 Publications1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X15183 mRNA. Translation: CAA33259.1.
    M27024 Genomic DNA. Translation: AAA63194.1.
    AJ890082 mRNA. Translation: CAI64495.1.
    AJ890083 mRNA. Translation: CAI64496.1.
    DQ314871 Genomic DNA. Translation: ABC40730.1.
    AK056446 mRNA. Translation: BAG51711.1.
    AK291115 mRNA. Translation: BAF83804.1.
    AK291607 mRNA. Translation: BAF84296.1.
    AL133223 Genomic DNA. No translation available.
    CH471061 Genomic DNA. Translation: EAW81765.1.
    X07270 mRNA. Translation: CAA30255.1.
    M30626 Genomic DNA. Translation: AAA36023.1.
    BC000987 mRNA. Translation: AAH00987.1.
    BC121062 mRNA. Translation: AAI21063.1.
    D87666 mRNA. Translation: BAA13430.1.
    D87666 mRNA. Translation: BAA13431.1.
    CCDSiCCDS32160.1. [P07900-2]
    CCDS9967.1. [P07900-1]
    PIRiA32319. HHHU86.
    RefSeqiNP_001017963.2. NM_001017963.2. [P07900-2]
    NP_005339.3. NM_005348.3. [P07900-1]
    UniGeneiHs.525600.

    Genome annotation databases

    EnsembliENST00000216281; ENSP00000216281; ENSG00000080824. [P07900-1]
    ENST00000334701; ENSP00000335153; ENSG00000080824. [P07900-2]
    GeneIDi3320.
    KEGGihsa:3320.
    UCSCiuc001yku.5. human. [P07900-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiHS90A_HUMAN
    AccessioniPrimary (citable) accession number: P07900
    Secondary accession number(s): A8K500
    , B3KPJ9, Q2PP14, Q5CAQ6, Q5CAQ7, Q9BVQ5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: January 23, 2007
    Last modified: August 30, 2017
    This is version 227 of the entry and version 5 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families