Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4TMVS9)

• DOT Name: Stress-70 protein, mitochondrial (HSPA9)
• Synonyms: 75 kDa glucose-regulated protein; GRP-75; Heat shock 70 kDa protein 9; Mortalin; MOT; Peptide-binding protein 74; PBP74
• Gene Name: HSPA9
• Related Disease:
  Autosomal dominant sideroblastic anemia
  Autosomal recessive sideroblastic anemia
  Even-plus syndrome
• UniProt ID: GRP75_HUMAN
• PDB ID: 3N8E; 4KBO; 6NHK; 6P2U; 6PMT
• Pfam ID: PF00012
• Sequence:
  MISASRAAAARLVGAAASRGPTAARHQDSWNGLSHEAFRLVSRRDYASEAIKGAVVGIDL
  GTTNSCVAVMEGKQAKVLENAEGARTTPSVVAFTADGERLVGMPAKRQAVTNPNNTFYAT
  KRLIGRRYDDPEVQKDIKNVPFKIVRASNGDAWVEAHGKLYSPSQIGAFVLMKMKETAEN
  YLGHTAKNAVITVPAYFNDSQRQATKDAGQISGLNVLRVINEPTAAALAYGLDKSEDKVI
  AVYDLGGGTFDISILEIQKGVFEVKSTNGDTFLGGEDFDQALLRHIVKEFKRETGVDLTK
  DNMALQRVREAAEKAKCELSSSVQTDINLPYLTMDSSGPKHLNMKLTRAQFEGIVTDLIR
  RTIAPCQKAMQDAEVSKSDIGEVILVGGMTRMPKVQQTVQDLFGRAPSKAVNPDEAVAIG
  AAIQGGVLAGDVTDVLLLDVTPLSLGIETLGGVFTKLINRNTTIPTKKSQVFSTAADGQT
  QVEIKVCQGEREMAGDNKLLGQFTLIGIPPAPRGVPQIEVTFDIDANGIVHVSAKDKGTG
  REQQIVIQSSGGLSKDDIENMVKNAEKYAEEDRRKKERVEAVNMAEGIIHDTETKMEEFK
  DQLPADECNKLKEEISKMRELLARKDSETGENIRQAASSLQQASLKLFEMAYKKMASERE
  GSGSSGTGEQKEDQKEEKQ
• Function: Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. May play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53. May play a role in the control of cell proliferation and cellular aging.
• KEGG Pathway:
  R. degradation (hsa03018)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  Cristae formation (R-HSA-8949613)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant sideroblastic anemia	DIS8SWG0	Strong	Autosomal dominant	[1]
Autosomal recessive sideroblastic anemia	DIS04G9O	Supportive	Autosomal recessive	[2]
Even-plus syndrome	DISOLM9N	Supportive	Autosomal recessive	[3]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Stress-70 protein, mitochondrial (HSPA9) decreases the response to substance of Cisplatin.	[39]
Sulforaphane	DMQY3L0	Investigative	Stress-70 protein, mitochondrial (HSPA9) affects the binding of Sulforaphane.	[40]

35 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[13]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[15]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[16]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[17]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[18]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[19]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[29]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[30]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Stress-70 protein, mitochondrial (HSPA9).	[31]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Stress-70 protein, mitochondrial (HSPA9).	[32]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[33]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[34]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[36]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[37]
Indirubin-3'-monoxime	DMLRQH0	Investigative	Indirubin-3'-monoxime increases the expression of Stress-70 protein, mitochondrial (HSPA9).	[38]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Stress-70 protein, mitochondrial (HSPA9).	[24]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Stress-70 protein, mitochondrial (HSPA9).	[35]

References

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