Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPI5OM0)

• DOT Name: 60 kDa heat shock protein, mitochondrial (HSPD1 HSP60 RCJMB04_7g5)
• Synonyms: EC 5.6.1.7; 60 kDa chaperonin; Chaperonin 60; CPN60; Heat shock protein 60; HSP-60; Hsp60
• Gene Name: HSPD1 HSP60 RCJMB04_7g5
• UniProt ID: CH60_CHICK
• EC Number: 5.6.1.7
• Pfam ID: PF00118
• Sequence:
  MLRLPAVLRQIRPVSRALAPHLTRAYAKDVKFGADARALMLQGVDLLADAVAVTMGPKGR
  TVIIEQSWGSPKVTKDGVTVAKAIDLKDKYKNIGAKLVQDVANNTNEEAGDGTTTATVLA
  RAIAKEGFEKISKGANPVEIRRGVMLAVDAITAELKKLSKPVTTPEEIAQVATISANGDQ
  EIGNIISDAMKKVGRKGVITVKDGKTLNDELEIIEGMKFDRGYISPYFINTAKGQKCEFQ
  DAYVLISEKKISSVQSIVPALEIANSHRKPLVIIAEDVDGEALSTLVLNRLKVGLQVVAV
  KAPGFGDNRKNQLKDMAIATGGAVFGEEGLSLNVEDIQPHDFGKVGEVIVTKDDTMLLKG
  KGEKAQIEKRIQEIIEQLEVTTSEYEKEKLNERLAKLSDGVAVLKVGGTSDVEVNEKKDR
  VTDALNATRAAVEEGIVPGGGCALLRCIPALDALKPANEDQKIGIEIIKRTLKIPAMTIA
  KNAGVEGSLIVEKILQSSSEVGYDAMLGEFVNMVEKGIIDPTKVVRTALMDAAGVASLLS
  TAEAVVTEVPKEEKEPAMGGMGGMGGGMGGGMF
• Function: Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.
• Reactome Pathway: Mitochondrial protein import (R-GGA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	60 kDa heat shock protein, mitochondrial (HSPD1 HSP60 RCJMB04_7g5) increases the Necrotising enterocolitis neonatal ADR of Arsenic trioxide.	[1]

References

• [1] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.