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Protein

Heat shock protein HSP 90-alpha

Gene

Hsp90aa1

Organism
Rattus norvegicus (Rat)
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. 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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei51ATPBy similarity1
Binding sitei93ATPBy similarity1
Binding sitei112ATPBy similarity1
Binding sitei138ATP; via amide nitrogenBy similarity1
Binding sitei401ATPBy similarity1

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: RGD
  • CTP binding Source: RGD
  • dATP binding Source: RGD
  • glycoprotein binding Source: ParkinsonsUK-UCL
  • GTP binding Source: RGD
  • ion channel binding Source: RGD
  • mRNA binding Source: RGD
  • nitric-oxide synthase regulator activity Source: UniProtKB
  • protein kinase binding Source: RGD
  • protein phosphatase binding Source: RGD
  • Rho GDP-dissociation inhibitor binding Source: RGD
  • sulfonylurea receptor binding Source: RGD
  • tau protein binding Source: RGD
  • TPR domain binding Source: UniProtKB
  • unfolded protein binding Source: RGD
  • UTP binding Source: RGD

GO - Biological processi

  • cardiac muscle cell apoptotic process Source: RGD
  • chaperone-mediated autophagy Source: ParkinsonsUK-UCL
  • chaperone-mediated protein transport involved in chaperone-mediated autophagy Source: ParkinsonsUK-UCL
  • neuron migration Source: RGD
  • positive regulation of cardiac muscle contraction Source: RGD
  • positive regulation of cell size Source: RGD
  • positive regulation of lamellipodium assembly Source: RGD
  • positive regulation of nitric oxide biosynthetic process Source: UniProtKB
  • positive regulation of protein import into nucleus, translocation Source: RGD
  • protein folding Source: RGD
  • regulation of protein complex stability Source: ParkinsonsUK-UCL
  • response to antibiotic Source: AgBase
  • response to cocaine Source: RGD
  • response to cold Source: AgBase
  • response to drug Source: RGD
  • response to estrogen Source: RGD
  • response to heat Source: RGD
  • response to salt stress Source: RGD
  • skeletal muscle contraction Source: RGD

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-1227986. Signaling by ERBB2.
R-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-RNO-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-RNO-203615. eNOS activation.
R-RNO-2565942. Regulation of PLK1 Activity at G2/M Transition.
R-RNO-3371497. HSP90 chaperone cycle for steroid hormone receptors (SHR).
R-RNO-3371511. HSF1 activation.
R-RNO-3371568. Attenuation phase.
R-RNO-3371571. HSF1-dependent transactivation.
R-RNO-380259. Loss of Nlp from mitotic centrosomes.
R-RNO-380270. Recruitment of mitotic centrosome proteins and complexes.
R-RNO-3928663. EPHA-mediated growth cone collapse.
R-RNO-399954. Sema3A PAK dependent Axon repulsion.
R-RNO-4420097. VEGFA-VEGFR2 Pathway.
R-RNO-5218920. VEGFR2 mediated vascular permeability.
R-RNO-5620912. Anchoring of the basal body to the plasma membrane.
R-RNO-6798695. Neutrophil degranulation.
R-RNO-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-RNO-8854518. AURKA Activation by TPX2.
R-RNO-8863795. Downregulation of ERBB2 signaling.

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
Gene namesi
Name:Hsp90aa1
Synonyms:Hsp86, Hspca
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi631409. Hsp90aa1.

Subcellular locationi

  • Cytoplasm By similarity
  • Melanosome By similarity
  • Cell membrane By similarity

GO - Cellular componenti

  • apical plasma membrane Source: RGD
  • basolateral plasma membrane Source: RGD
  • brush border membrane Source: RGD
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • extracellular matrix Source: RGD
  • lysosomal membrane Source: ParkinsonsUK-UCL
  • melanosome Source: UniProtKB-SubCell
  • myelin sheath Source: UniProtKB
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • nucleus Source: AgBase
  • perinuclear region of cytoplasm Source: RGD
  • protein complex Source: RGD
  • sperm flagellum Source: RGD
  • sperm mitochondrial sheath Source: RGD
  • sperm plasma membrane Source: RGD

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000629152 – 733Heat shock protein HSP 90-alphaAdd BLAST732

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphothreonine; by PRKDCBy similarity1
Modified residuei7Phosphothreonine; by PRKDCBy similarity1
Modified residuei58N6-acetyllysineBy similarity1
Modified residuei84N6-acetyllysineBy similarity1
Modified residuei231PhosphoserineCombined sources1
Modified residuei252PhosphoserineCombined sources1
Modified residuei263PhosphoserineCombined sources1
Modified residuei314PhosphotyrosineBy similarity1
Modified residuei400PhosphoserineBy similarity1
Modified residuei444N6-acetyllysineBy similarity1
Modified residuei454PhosphoserineCombined sources1
Modified residuei459N6-acetyllysineBy similarity1
Modified residuei477PhosphoserineBy similarity1
Modified residuei490N6-acetyllysineBy similarity1
Modified residuei493PhosphotyrosineBy similarity1
Modified residuei586N6-acetyllysineBy similarity1
Modified residuei599S-nitrosocysteineBy similarity1
Modified residuei642PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiP82995.
PRIDEiP82995.

PTM databases

iPTMnetiP82995.

Expressioni

Gene expression databases

BgeeiENSRNOG00000007219.
GenevisibleiP82995. RN.

Interactioni

Subunit structurei

Homodimer. 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. Interacts with TOM34. Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex. Interacts with CHORDC1 and DNAJC7. Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems. Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity. Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8. Interacts with KSR1. Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity. May interact with NWD1. Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity. Interacts with AHSA1; the interaction activates HSP90AA1 ATPase activity. Interacts with FLCN in the presence of FNIP1. Interacts with HSP70, STIP1 and PTGES3 (By similarity). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase. Interacts with TTC1 (via TPR repeats). Interacts with HSF1 in an ATP-dependent manner. 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 (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. Interacts with STUB1 and SMAD3 (By similarity). Interacts with HSP90AB1; interaction is constitutive (By similarity).By similarity1 Publication

GO - Molecular functioni

  • glycoprotein binding Source: ParkinsonsUK-UCL
  • ion channel binding Source: RGD
  • protein kinase binding Source: RGD
  • protein phosphatase binding Source: RGD
  • Rho GDP-dissociation inhibitor binding Source: RGD
  • sulfonylurea receptor binding Source: RGD
  • tau protein binding Source: RGD
  • TPR domain binding Source: UniProtKB
  • unfolded protein binding Source: RGD

Protein-protein interaction databases

BioGridi256205. 20 interactors.
IntActiP82995. 2 interactors.
MINTiMINT-1775917.
STRINGi10116.ENSRNOP00000009556.

Structurei

3D structure databases

ProteinModelPortaliP82995.
SMRiP82995.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni285 – 733Interaction with FLCN and FNIP1By similarityAdd BLAST449
Regioni285 – 621Interaction with FNIP2By similarityAdd BLAST337
Regioni683 – 733Required for homodimerizationBy similarityAdd BLAST51
Regioni729 – 733Essential for interaction with SMYD3By similarity5
Regioni730 – 733Essential for interaction with SGTA and TTC1By similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi724 – 733TPR 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

eggNOGiKOG0019. Eukaryota.
KOG0020. Eukaryota.
COG0326. LUCA.
GeneTreeiENSGT00840000129758.
HOGENOMiHOG000031988.
HOVERGENiHBG007374.
InParanoidiP82995.
KOiK04079.
OMAiYESFGKN.
OrthoDBiEOG091G0270.
PhylomeDBiP82995.
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.

Sequencei

Sequence statusi: Complete.

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

P82995-1 [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 TVRTDTGEPM GRGTKVILHL KEDQTEYLEE
210 220 230 240 250
RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKEE KEEEKEKEEK
260 270 280 290 300
ESDDKPEIED VGSDEEEEEK KDGDKKKKKK IKEKYIDQEE LNKTKPIWTR
310 320 330 340 350
NPDDITNEEY GEFYKSLTND WEEHLAVKHF SVEGQLEFRA LLFVPRRAPF
360 370 380 390 400
DLFENRKKKN NIKLYVRRVF IMDNCEELIP EYLNFIRGVV DSEDLPLNIS
410 420 430 440 450
REMLQQSKIL KVIRKNLVKK CLELFTELAE DKENYKKFYE QFSKNIKLGI
460 470 480 490 500
HEDSQNRKKL SELLRYYTSA SGDEMVSLKD YCTRMKENQK HIYFITGETK
510 520 530 540 550
DQVANSAFVE RLRKHGLEVI YMIEPIDEYC VQQLKEFEGK TLVSVTKEGL
560 570 580 590 600
ELPEDEEEKK KQEEKKTKFE NLCKIMKDIL EKKVEKVVVS NRLVTSPCCI
610 620 630 640 650
VTSTYGWTAN MERIMKAQAL RDNSTMGYMA AKKHLEINPD HSIIETLRQK
660 670 680 690 700
AEADKNDKSV KDLVILLYET ALLSSGFSLE DPQTHANRIY RMIKLGLGID
710 720 730
EDDPTVDDTS AAVTEEMPPL EGDDDTSRME EVD
Length:733
Mass (Da):84,815
Last modified:January 23, 2007 - v3
Checksum:iDF2C8383A6581D07
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ297736 Genomic DNA. Translation: CAC39453.1.
AJ428213 mRNA. Translation: CAD21648.1.
BC072489 mRNA. Translation: AAH72489.1.
BC085120 mRNA. Translation: AAH85120.1.
RefSeqiNP_786937.1. NM_175761.2.
XP_008763191.1. XM_008764969.2.
UniGeneiRn.119867.
Rn.231905.
Rn.232226.
Rn.3277.

Genome annotation databases

EnsembliENSRNOT00000009556; ENSRNOP00000009556; ENSRNOG00000007219.
ENSRNOT00000086310; ENSRNOP00000075715; ENSRNOG00000059714.
GeneIDi103692716.
299331.
KEGGirno:103692716.
rno:299331.
UCSCiRGD:631409. rat.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiHS90A_RAT
AccessioniPrimary (citable) accession number: P82995
Secondary accession number(s): Q91XW0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: January 23, 2007
Last modified: June 7, 2017
This is version 130 of the entry and version 3 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families