General Information of Binding Target of SBP (BTS) (ID: ST00153)
BTS Name
Heat shock protein HSP 90-beta
Synonyms
HSP 90; Heat shock 84 kDa; HSP 84; HSP84
BTS Type
Protein
Family
Heat shock protein 90 family
Gene Name
HSP90AB1
Organism
Homo sapiens (Human)
Function
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 linked to its ATPase 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. They first 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 Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10
UniProt ID
P08238
UniProt Entry
HS90B_HUMAN
PFam
PF02518 ; PF00183
Gene ID
3326
Sequence
MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLT
DPSKLDSGKELKIDIIPNPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAG
ADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTK
VILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEE
DKDDEEKPKIEDVGSDEEDDSGKDKKKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEE
YGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKKKKNNIKLYVRRV
FIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKCLELFSELA
EDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELLRYHTSQSGDEMTSLSEYVSRMKETQ
KSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFDGKSLVSVTKEG
LELPEDEEEKKKMEESKAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIVTSTYGWTA
NMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVKDLVVLLFE
TALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRM
EEVD
Sequence Length
724
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Designed TPR protein anti-hsp90 CTPR390 Research Binder Kd: 200000 nM Tools for understanding peptide ligand recognition
SBP Info
[1]
Designed TPR protein anti-hsp90 CTPR390+ Research Binder Kd: 1000 nM Cancers [ICD-11: 2D4Z]
SBP Info
[2]
Designed TPR protein anti-hsp90 D334K mutant Research Binder Kd: 250 nM Cancers [ICD-11: 2D4Z]
SBP Info
[3]
Designed TPR protein anti-HSP90/Hsp70 D334K/T332R double mutant Research Binder Kd: 60 nM Cancers [ICD-11: 2D4Z]
SBP Info
[3]
scFv Efungumab Phase III Inhibitor N.A. Cryptococcal Meningitis [ICD-11: 1D01.10]; Breast cancer [ICD-11: 2C6Z]
SBP Info
[4]
References
1 Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins. Protein Eng Des Sel. 2004 Apr;17(4):399-409.
2 Designed TPR modules as novel anticancer agents. ACS Chem Biol. 2008 Mar 20;3(3):161-6.
3 Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90: computational analysis and protein engineering. J Biol Chem. 2009 Sep 11;284(37):25364-74.
4 Efungumab: a novel agent in the treatment of invasive candidiasis. Ann Pharmacother. 2009 Nov;43(11):1818-23.