Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8QM7K)

• DOT Name: Calpain-5 (CAPN5)
• Synonyms: EC 3.4.22.-; Calpain htra-3; New calpain 3; nCL-3
• Gene Name: CAPN5
• Related Disease:
  CAPN5-related vitreoretinopathy
  Neoplasm
  Age-related macular degeneration
  Autosomal recessive limb-girdle muscular dystrophy type 2A
  Breast cancer
  Cardiovascular disease
  Diabetic cataract
  Eosinophilic esophagitis
  Hepatitis C virus infection
  Polycystic ovarian syndrome
  Proliferative diabetic retinopathy
  Rhegmatogenous retinal detachment
  Vitreoretinal degeneration
  X-linked reticulate pigmentary disorder
  Disorder of orbital region
  Obsolete autosomal dominant neovascular inflammatory vitreoretinopathy
  Advanced cancer
  Blindness
  Epilepsy
  High blood pressure
  Meningioma
  Neurofibromatosis type 2
  Non-insulin dependent diabetes
  Obesity
  Proliferative vitreoretinopathy
  Retinoblastoma
  Thyroid tumor
  Uveitis
• UniProt ID: CAN5_HUMAN
• PDB ID: 6P3Q
• EC Number: 3.4.22.-
• Pfam ID: PF00168 ; PF01067 ; PF00648
• Sequence:
  MFSCVKPYEDQNYSALRRDCRRRKVLFEDPLFPATDDSLYYKGTPGPAVRWKRPKGICED
  PRLFVDGISSHDLHQGQVGNCWFVAACSSLASRESLWQKVIPDWKEQEWDPEKPNAYAGI
  FHFHFWRFGEWVDVVIDDRLPTVNNQLIYCHSNSRNEFWCALVEKAYAKLAGCYQALDGG
  NTADALVDFTGGVSEPIDLTEGDFANDETKRNQLFERMLKVHSRGGLISASIKAVTAADM
  EARLACGLVKGHAYAVTDVRKVRLGHGLLAFFKSEKLDMIRLRNPWGEREWNGPWSDTSE
  EWQKVSKSEREKMGVTVQDDGEFWMTFEDVCRYFTDIIKCRVINTSHLSIHKTWEEARLH
  GAWTLHEDPRQNRGGGCINHKDTFFQNPQYIFEVKKPEDEVLICIQQRPKRSTRREGKGE
  NLAIGFDIYKVEENRQYRMHSLQHKAASSIYINSRSVFLRTDQPEGRYVIIPTTFEPGHT
  GEFLLRVFTDVPSNCRELRLDEPPHTCWSSLCGYPQLVTQVHVLGAAGLKDSPTGANSYV
  IIKCEGDKVRSAVQKGTSTPEYNVKGIFYRKKLSQPITVQVWNHRVLKDEFLGQVHLKAD
  PDNLQALHTLHLRDRNSRQPSNLPGTVAVHILSSTSLMAV
• Function: Calcium-regulated non-lysosomal thiol-protease.
• Tissue Specificity: Expressed in many tissues. Strong expression in the photoreceptor cells of the retina, with a punctate pattern of labeling over the nuclei and inner segments with less expression along the other segments and outer plexiform layer.
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CAPN5-related vitreoretinopathy	DISJGUBM	Definitive	Autosomal dominant	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Autosomal recessive limb-girdle muscular dystrophy type 2A	DISIHX4S	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Diabetic cataract	DISKRB4V	Strong	Altered Expression	[7]
Eosinophilic esophagitis	DISR8WSB	Strong	Genetic Variation	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[6]
Proliferative diabetic retinopathy	DISQZ13G	Strong	Biomarker	[3]
Rhegmatogenous retinal detachment	DISLE27J	Strong	Biomarker	[3]
Vitreoretinal degeneration	DISVPRKD	Strong	Biomarker	[3]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Genetic Variation	[3]
Disorder of orbital region	DISH0ECJ	moderate	Biomarker	[10]
Obsolete autosomal dominant neovascular inflammatory vitreoretinopathy	DISUON6F	Moderate	Autosomal dominant	[11]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[10]
Blindness	DISTIM10	Limited	Biomarker	[12]
Epilepsy	DISBB28L	Limited	Genetic Variation	[10]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[13]
Meningioma	DISPT4TG	Limited	Biomarker	[14]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[14]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[13]
Obesity	DIS47Y1K	Limited	Genetic Variation	[15]
Proliferative vitreoretinopathy	DISZTEK1	Limited	Biomarker	[3]
Retinoblastoma	DISVPNPB	Limited	Altered Expression	[10]
Thyroid tumor	DISLVKMD	Limited	Genetic Variation	[16]
Uveitis	DISV0RYS	Limited	Genetic Variation	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calpain-5 (CAPN5).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calpain-5 (CAPN5).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calpain-5 (CAPN5).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calpain-5 (CAPN5).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calpain-5 (CAPN5).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Calpain-5 (CAPN5).	[23]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Calpain-5 (CAPN5).	[24]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Calpain-5 (CAPN5).	[25]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Calpain-5 (CAPN5).	[26]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Calpain-5 (CAPN5).	[27]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Calpain-5 (CAPN5).	[28]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Calpain-5 (CAPN5).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Calpain-5 (CAPN5).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Calpain-5 (CAPN5).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Calpain-5 (CAPN5).	[32]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Calpain-5 (CAPN5).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calpain-5 (CAPN5).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Calpain-5 (CAPN5).	[34]

References

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• [17] Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular retinal detachment.PLoS One. 2015 Apr 9;10(4):e0122352. doi: 10.1371/journal.pone.0122352. eCollection 2015.
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