Hsp90 alpha
Human Recombinant HSP90AA1 - His Tagged
Reference ID:KB-2260
Western Blot
Gene of Interest
Gene Synonyms:HSP90AA1;HSP90A;HSPC1;HSPCA
Protein Names:Heat shock protein HSP 90-alpha (Heat shock 86 kDa) (HSP 86) (HSP86) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38)
Accession Data
Organism:Homo sapiens (Human)
Mass (kDa):846.60
Length (aa):732
Sequence:MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIRYESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPMGRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKEDKEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRNPDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNNIKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKCLELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDYCTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKTLVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIVTSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVKDLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLEGDDDTSRMEEVD
Proteomics (Proteome ID):UP000005640
Proteomics (Chromosome): Chromosome 14
Activity Regulation: In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). 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 (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155). {ECO:0000269|PubMed:18400751, ECO:0000269|PubMed:29127155}.
Binding Site:BINDING 51 51 ATP.; BINDING 93 93 ATP.; BINDING 112 112 ATP. {ECO:0000250}.; BINDING 138 138 ATP; via amide nitrogen.; BINDING 400 400 ATP. {ECO:0000250}.
Function [CC]: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, PubMed:29127155). 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 (PubMed:29127155). 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 (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). 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 (PubMed:25973397). 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). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.
Kinetics:BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=300 uM for ATP {ECO:0000269|PubMed:18400751};
Mutagenesis:MUTAGEN 47 47 E->A: Strong ATP-binding. Strong interaction with HSF1, HIF1A, ERBB2, MET, KEAP1 and RHOBTB2. No effect on interaction with TSC1. {ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:29127155}.; MUTAGEN 93 93 D->A: Impaired ATP-binding. Strong interaction with HIF1A, MET, KEAP1 and RHOBTB2. Loss of interaction with HSF1 and ERBB2. Los of interaction with TSC1. {ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:29127155}.; MUTAGEN 97 97 G->D: Abolishes ATPase activity. {ECO:0000269|PubMed:18256191}.; MUTAGEN 313 313 Y->E: Loss of interaction with TSC1 and increases interacrion with AHSA1. {ECO:0000269|PubMed:29127155}.; MUTAGEN 313 313 Y->F: No deffect on the interaction with TSC1. {ECO:0000269|PubMed:29127155}.; MUTAGEN 598 598 C->A,N,D: Reduces ATPase activity and client protein activation. {ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:19696785}.; MUTAGEN 598 598 C->S: Loss of S-nitrosylation. {ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:19696785}.; MUTAGEN 728 732 Missing: Loss of interaction with TSC1. {ECO:0000269|PubMed:29127155}.
Reagent Data
Name:Hsp90 alpha
Class:Heat Shock
Subcategory:Protein
Molecular Weight:86.8
Source:E.Coli
Species:Human
Tag:His
Amino Acid Sequence:MGSSHHHHHH SSGLVPRGSH MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR YESLTDPSKL DSGKELHINL IPNKQDRTLT IVDTGIGMTK ADLINNLGTI AKSGTKAFME ALQAGADISM IGQFGVGFYS AYLVAEKVTV ITKHNDDEQY AWESSAGGSF TVRTDTGEPM GRGTKVILHL KEDQTEYLEE RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKED KEEEKEKEEK ESEDKPEIED VGSDEEEEKK DGDKKKKKKI KEKYIDQEEL NKTKPIWTRN PDDITNEEYG EFYKSLTNDW EDHLAVKHFS VEGQLEFRAL LFVPRRAPFD LFENRKKKNN IKLYVRRVFI MDNCEELIPE YLNFIRGVVD SEDLPLNISR EMLQQSKILK VIRKNLVKKC LELFTELAED KENYKKFYEQ FSKNIKLGIH EDSQNRKKLS ELLRYYTSAS GDEMVSLKDY CTRMKENQKH IYYITGETKD QVANSAFVER LRKHGLEVIY MIEPIDEYCV QQLKEFEGKT LVSVTKEGLE LPEDEEEKKK QEEKKTKFEN LCKIMKDILE KKVEKVVVSN RLVTSPCCIV TSTYGWTANM ERIMKAQALR DNSTMGYMAA KKHLEINPDH SIIETLRQKA EADKNDKSVK DLVILLYETA LLSSGFSLEDPQTHANRIYR MIKLGLGIDE DDPTADDTSA AVTEEMPPLE GDDDTSRMEE VD
Bioactivity
Measured:2x10^7 IU/mg
Determined By:Assay (Variable)
Assay Profile:LOT-Specific (Check COA)
Format:Solution
Formulation:Sterile-filtered colorless solution
Formulation Concentration:1 mg/ml
Buffer Volume:20 mM
Buffer Solution: Tris-HCl
pH:7.4
Stabilizers
NaCl:100 mM
Purity:> 90%
Determined: SDS-PAGE
Sample Handling
Storage:4°C
Stability:This bioreagent is stable at 4°C (short-term) and -70°C(long-term). After reconstitution, sample may be stored at 4°C for 2-7 days and below -18°C for future use.
Preparation:Reconstitute in sterile distilled H2O to no less than 100 ug/ml; dilute reconstituted stock further in other aqueous solutions if needed. Please review COA for lot-specific instructions. Final measurements should be determined by the end-user for optimal performance.