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Entry version 134 (07 Oct 2020)
Sequence version 2 (28 Jun 2011)
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Heat shock protein HSP 90-alpha



Oryctolagus cuniculus (Rabbit)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. 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. 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. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation.By similarity

<p>This subsection of the <a href="">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity 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. Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity. Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity. Inhibited by Ganetespib (STA-9090) and SNX-2112.By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei51ATPBy similarity1
Binding sitei93ATPBy similarity1
Binding sitei112ATPBy similarity1
Binding sitei138ATP; via amide nitrogenBy similarity1
Binding sitei376ATPBy similarity1

<p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Heat shock protein HSP 90-alpha
<p>This subsection of the <a href="">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
<p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiOryctolagus cuniculus (Rabbit)
<p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9986 [NCBI]
<p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
<p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000001811 <p>A UniProt <a href="">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unplaced

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedBy similarity
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004098182 – 694Heat shock protein HSP 90-alphaBy similarityAdd BLAST693

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="">lipids</a>, <a href="">glycans</a> and <a href="">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei5Phosphothreonine; by PRKDC1 Publication1
Modified residuei7Phosphothreonine; by PRKDC1 Publication1
Modified residuei58N6-acetyllysineBy similarity1
Modified residuei84N6-acetyllysineBy similarity1
Modified residuei231PhosphoserineBy similarity1
Modified residuei249PhosphoserineBy similarity1
Modified residuei289PhosphotyrosineBy similarity1
Modified residuei419N6-acetyllysineBy similarity1
Modified residuei429PhosphoserineBy similarity1
Modified residuei434N6-acetyllysineBy similarity1
Modified residuei452PhosphoserineBy similarity1
Modified residuei465N6-acetyllysineBy similarity1
Modified residuei468PhosphotyrosineBy similarity1
Modified residuei547N6-acetyllysineBy similarity1
Modified residuei560S-nitrosocysteineBy similarity1
Modified residuei603PhosphoserineBy similarity1

<p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

ISGylated.By similarity
S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.By similarity
Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation, Ubl conjugation

PTM databases

iPTMnet integrated resource for PTMs in systems biology context


<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (By similarity). 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:9195923).

Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By similarity). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (By similarity).

Interacts with TOM34 (By similarity).

Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (By similarity).

Interacts with CHORDC1 and DNAJC7 (By similarity).

Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (By similarity).

Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (By similarity). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (By similarity).

Interacts with KSR1 (By similarity).

Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (By similarity). May interact with NWD1 (By similarity).

Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (By similarity).

Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (By similarity).

Interacts with FLCN in the presence of FNIP1 (By similarity).

Interacts with HSP70, STIP1 and PTGES3 (By similarity).

Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase.

Interacts with SGTA (via TPR repeats) (By similarity).

Interacts with TTC1 (via TPR repeats) (By similarity).

Interacts with HSF1 in an ATP-dependent manner (By similarity).

Interacts with MET; the interaction suppresses MET kinase activity (By similarity).

Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (By similarity).

Interacts with HIF1A, KEAP1 and RHOBTB2 (By similarity).

Interacts with HIF1A, KEAP1 and RHOBTB2 (By similarity).

Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (By similarity).

Interacts with STUB1 and SMAD3 (By similarity).

Interacts with HSP90AB1; interaction is constitutive (By similarity).

Interacts with HECTD1 (via N-terminus) (By similarity).

Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity).

Interacts with NLPR12.

Interacts with PDCL3 (By similarity).

By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRING: functional protein association networks


<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

Biological Magnetic Resonance Data Bank


SWISS-MODEL Repository - a database of annotated 3D protein structure models


Database of comparative protein structure models


<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni9 – 236Interaction with NR3C1By similarityAdd BLAST228
Regioni258 – 578Interaction with NR3C1By similarityAdd BLAST321
Regioni261 – 694Interaction with FLCN and FNIP1By similarityAdd BLAST434
Regioni261 – 582Interaction with FNIP2 and TSC1By similarityAdd BLAST322
Regioni590 – 693Interaction with NR1D1By similarityAdd BLAST104
Regioni644 – 694Required for homodimerizationBy similarityAdd BLAST51
Regioni690 – 694Essential for interaction with SMYD3, TSC1 and STIP1/HOPBy similarity5
Regioni691 – 694Essential for interaction with SGTA and TTC1By similarity4


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi685 – 694TPR repeat-bindingBy similarity10

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the heat shock protein 90 family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

KOG0019, Eukaryota

InParanoid: Eukaryotic Ortholog Groups


TreeFam database of animal gene trees


Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

Gene3Di, 1 hit
3.30.565.10, 1 hit

HAMAP database of protein families

MF_00505, HSP90, 1 hit

Integrated resource of protein families, domains and functional sites

View protein in InterPro
IPR003594, HATPase_C
IPR036890, HATPase_C_sf
IPR019805, Heat_shock_protein_90_CS
IPR037196, HSP90_C
IPR001404, Hsp90_fam
IPR020575, Hsp90_N
IPR020568, Ribosomal_S5_D2-typ_fold

The PANTHER Classification System

PTHR11528, PTHR11528, 1 hit

Pfam protein domain database

View protein in Pfam
PF02518, HATPase_c, 1 hit
PF00183, HSP90, 1 hit

PIRSF; a whole-protein classification database

PIRSF002583, Hsp90, 1 hit

Protein Motif fingerprint database; a protein domain database


Simple Modular Architecture Research Tool; a protein domain database

View protein in SMART
SM00387, HATPase_c, 1 hit

Superfamily database of structural and functional annotation

SSF110942, SSF110942, 1 hit
SSF54211, SSF54211, 1 hit
SSF55874, SSF55874, 1 hit

PROSITE; a protein domain and family database

View protein in PROSITE
PS00298, HSP90, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="">length</a> and <a href="">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

P30946-1 [UniParc]FASTAAdd to basket
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Mass (Da):79,733
Last modified:June 28, 2011 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB080801B6C141D05

Sequence databases

Protein sequence database of the Protein Information Resource


<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases


3D structure databases


Protein-protein interaction databases


PTM databases


Phylogenomic databases

eggNOGiKOG0019, Eukaryota

Family and domain databases

Gene3Di1.20.120.790, 1 hit
3.30.565.10, 1 hit
HAMAPiMF_00505, HSP90, 1 hit
InterProiView protein in InterPro
IPR003594, HATPase_C
IPR036890, HATPase_C_sf
IPR019805, Heat_shock_protein_90_CS
IPR037196, HSP90_C
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
SMARTiView protein in SMART
SM00387, HATPase_c, 1 hit
SUPFAMiSSF110942, SSF110942, 1 hit
SSF54211, SSF54211, 1 hit
SSF55874, SSF55874, 1 hit
PROSITEiView protein in PROSITE
PS00298, HSP90, 1 hit

ProtoNet; Automatic hierarchical classification of proteins


MobiDB: a database of protein disorder and mobility annotations


<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHS90A_RABIT
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P30946
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: June 28, 2011
Last modified: October 7, 2020
This is version 134 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Direct protein sequencing, Reference proteome


  1. SIMILARITY comments
    Index of protein domains and families
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