Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Heat shock protein HSP 90-alpha

Gene

HSP90AA1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: -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. 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

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. 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei51ATPBy similarity1
Binding sitei93ATPBy similarity1
Binding sitei112ATPBy similarity1
Binding sitei138ATP; via amide nitrogenBy similarity1
Binding sitei376ATPBy similarity1

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB
  • phosphoprotein binding Source: AgBase
  • unfolded protein binding Source: InterPro

GO - Biological processi

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock protein HSP 90-alpha
Gene namesi
Name:HSP90AA1
Synonyms:HSPCA
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004098182 – 694Heat shock protein HSP 90-alphaBy similarityAdd BLAST693

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 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

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

Proteomic databases

PRIDEiP30946

PTM databases

iPTMnetiP30946

Interactioni

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).By similarity1 Publication

GO - Molecular functioni

  • phosphoprotein binding Source: AgBase
  • unfolded protein binding Source: InterPro

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000001106

Structurei

3D structure databases

ProteinModelPortaliP30946
SMRiP30946
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni261 – 694Interaction with FLCN and FNIP1By similarityAdd BLAST434
Regioni261 – 582Interaction with FNIP2 and TSC1By similarityAdd BLAST322
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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi685 – 694TPR repeat-bindingBy similarity10

Domaini

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

Sequence similaritiesi

Belongs to the heat shock protein 90 family.Curated

Phylogenomic databases

eggNOGiKOG0020 Eukaryota
COG0326 LUCA
HOGENOMiHOG000031988
InParanoidiP30946
TreeFamiTF300686

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
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
PRINTSiPR00775 HEATSHOCK90
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

Sequencei

Sequence statusi: Complete.

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

P30946-1 [UniParc]FASTAAdd to basket

« 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 TVRTDAGEPM GRGTKVVLHL KEDQTEYLEE
210 220 230 240 250
RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAKQPDD KPEIEDVGSD
260 270 280 290 300
EEEEEKKDGD IDQEELNKTK PIWTRNPDDI TNEEYGEFYK SLTNDWEDHL
310 320 330 340 350
AVKHFSVEGQ LEFRALLFVP RRAPFDLFEN RKKKNNIKLY VRRVFIMDNC
360 370 380 390 400
EELIPEYLNF IRGVVDSEDL PLNISREMLQ QSKILKVIRK NLVKKCLELF
410 420 430 440 450
TELAEDKENY KKFYEQFSKN IKLGIHEDSQ NRKKLSELLR YYTSASGDEM
460 470 480 490 500
VSLKDYCTRM KENQKHIYYI TGETKDQVAN SAFVERLRKH GLEVIYMIEP
510 520 530 540 550
IDEYCVQQLK EFEGKTLVSV TKEGLELTKF ENLCKIMKDI LEKKVEKVVV
560 570 580 590 600
SNRLVTSPCC IVTSTYGWTA NMERIMKAQA LRDNSTMGYM AAKKHLEVNP
610 620 630 640 650
DHSIIETLRQ KAEADKNDKS VKDLVILLYE TALLSSGFSL EDPQTHANRI
660 670 680 690
YRMIKLGLGI DEDDPTADDT AAAVTEEMPP LEGDDDTSRM EEVD
Length:694
Mass (Da):79,733
Last modified:June 28, 2011 - v2
Checksum:iB080801B6C141D05
GO

Sequence databases

PIRiA34461

Similar proteinsi

Entry informationi

Entry nameiHS90A_RABIT
AccessioniPrimary (citable) accession number: P30946
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: June 28, 2011
Last modified: April 25, 2018
This is version 125 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health