Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIAPE5J)

• DOT Name: Calpain-2 catalytic subunit (CAPN2)
• Synonyms: EC 3.4.22.53; Calcium-activated neutral proteinase 2; CANP 2; Calpain M-type; Calpain large polypeptide L2; Calpain-2 large subunit; Millimolar-calpain; M-calpain
• Gene Name: CAPN2
• UniProt ID: CAN2_HUMAN
• PDB ID: 1KFU; 1KFX; 2NQA
• EC Number: 3.4.22.53
• Pfam ID: PF01067 ; PF13833 ; PF00648
• Sequence:
  MAGIAAKLAKDREAAEGLGSHDRAIKYLNQDYEALRNECLEAGTLFQDPSFPAIPSALGF
  KELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEI
  LARVVPLNQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSAL
  LEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELKKPPPNLFKIIQKALQKGSLLGC
  SIDITSAADSEAITFQKLVKGHAYSVTGAEEVESNGSLQKLIRIRNPWGEVEWTGRWNDN
  CPSWNTIDPEERERLTRRHEDGEFWMSFSDFLRHYSRLEICNLTPDTLTSDTYKKWKLTK
  MDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDEEDGESGCTFLVGLIQKHRRRQR
  KMGEDMHTIGFGIYEVPEELSGQTNIHLSKNFFLTNRARERSDTFINLREVLNRFKLPPG
  EYILVPSTFEPNKDGDFCIRVFSEKKADYQAVDDEIEANLEEFDISEDDIDDGFRRLFAQ
  LAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYIL
  WTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKMPCQLHQVIVARFADDQLIIDFD
  NFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLCFSVL
• Function: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226'. Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
  Cellular senescence (hsa04218)
  Focal adhesion (hsa04510)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Shigellosis (hsa05131)
• Reactome Pathway:
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Calpain-2 catalytic subunit (CAPN2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calpain-2 catalytic subunit (CAPN2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calpain-2 catalytic subunit (CAPN2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Calpain-2 catalytic subunit (CAPN2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Calpain-2 catalytic subunit (CAPN2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Calpain-2 catalytic subunit (CAPN2).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Calpain-2 catalytic subunit (CAPN2).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calpain-2 catalytic subunit (CAPN2).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Calpain-2 catalytic subunit (CAPN2).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[15]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Calpain-2 catalytic subunit (CAPN2).	[16]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Calpain-2 catalytic subunit (CAPN2).	[17]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Calpain-2 catalytic subunit (CAPN2).	[18]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide increases the expression of Calpain-2 catalytic subunit (CAPN2).	[19]
Glimepiride	DM5FSJA	Approved	Glimepiride increases the expression of Calpain-2 catalytic subunit (CAPN2).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Calpain-2 catalytic subunit (CAPN2).	[20]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Calpain-2 catalytic subunit (CAPN2).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[21]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Calpain-2 catalytic subunit (CAPN2).	[11]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Calpain-2 catalytic subunit (CAPN2).	[25]
HONOKIOL	DMJWT3X	Investigative	HONOKIOL increases the expression of Calpain-2 catalytic subunit (CAPN2).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Calpain-2 catalytic subunit (CAPN2).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calpain-2 catalytic subunit (CAPN2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
G418	DMKTJBU	Investigative	G418 increases the cleavage of Calpain-2 catalytic subunit (CAPN2).	[27]

References

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