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Protein

Heat shock protein HSP 90-alpha

Gene

HSP90AA1

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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

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
ORF Names:QtrA-10430
OrganismiMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Taxonomic identifieri9541 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002717071 – 733Heat shock protein HSP 90-alphaAdd BLAST733

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 residuei231PhosphoserineBy similarity1
Modified residuei252PhosphoserineBy similarity1
Modified residuei263PhosphoserineBy similarity1
Modified residuei314PhosphotyrosineBy similarity1
Modified residuei400PhosphoserineBy similarity1
Modified residuei444N6-acetyllysineBy similarity1
Modified residuei454PhosphoserineBy similarity1
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

PRIDEiQ4R4P1.

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. Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase. Interacts with SGTA (via TPR repeats). 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. 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. Interacts with HSP90AB1; interaction is constitutive.By similarity

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliQ4R4P1.
SMRiQ4R4P1.
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

HOVERGENiHBG007374.
KOiK04079.

Family and domain databases

CDDicd00075. HATPase_c. 1 hit.
Gene3Di3.30.565.10. 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.

Q4R4P1-1 [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 SDDEAEEKED KEEEKEKEEK
260 270 280 290 300
ESEDKPEIED VGSDEEEEEK KDGDKKKKKK IKEKYIDQEE LNKTKPIWTR
310 320 330 340 350
NPDDITNEEY GEFYKSLTND WEDHLAVKHF 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 HIYYITGETK
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
EDDPTADDTS AAVTEEMPPL EGDDDTSRME EVD
Length:733
Mass (Da):84,789
Last modified:January 23, 2007 - v3
Checksum:i4DF7F56B0EA460C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB169853 mRNA. Translation: BAE01934.1.
RefSeqiNP_001270868.1. NM_001283939.1.
UniGeneiMfa.8198.

Genome annotation databases

GeneIDi101866865.
KEGGimcf:101866865.

Similar proteinsi

Entry informationi

Entry nameiHS90A_MACFA
AccessioniPrimary (citable) accession number: Q4R4P1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 83 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families