Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE6J88E)

• DOT Name: Caspase-10 (CASP10)
• Synonyms: CASP-10; EC 3.4.22.63; Apoptotic protease Mch-4; FAS-associated death domain protein interleukin-1B-converting enzyme 2; FLICE2; ICE-like apoptotic protease 4
• Gene Name: CASP10
• Related Disease:
  Autoimmune lymphoproliferative syndrome type 2A
  Autoimmune lymphoproliferative syndrome
• UniProt ID: CASPA_HUMAN
• EC Number: 3.4.22.63
• Pfam ID: PF01335 ; PF00656
• Sequence:
  MKSQGQHWYSSSDKNCKVSFREKLLIIDSNLGVQDVENLKFLCIGLVPNKKLEKSSSASD
  VFEHLLAEDLLSEEDPFFLAELLYIIRQKKLLQHLNCTKEEVERLLPTRQRVSLFRNLLY
  ELSEGIDSENLKDMIFLLKDSLPKTEMTSLSFLAFLEKQGKIDEDNLTCLEDLCKTVVPK
  LLRNIEKYKREKAIQIVTPPVDKEAESYQGEEELVSQTDVKTFLEALPQESWQNKHAGSN
  GNRATNGAPSLVSRGMQGASANTLNSETSTKRAAVYRMNRNHRGLCVIVNNHSFTSLKDR
  QGTHKDAEILSHVFQWLGFTVHIHNNVTKVEMEMVLQKQKCNPAHADGDCFVFCILTHGR
  FGAVYSSDEALIPIREIMSHFTALQCPRLAEKPKLFFIQACQGEEIQPSVSIEADALNPE
  QAPTSLQDSIPAEADFLLGLATVPGYVSFRHVEEGSWYIQSLCNHLKKLVPRMLKFLEKT
  MEIRGRKRTVWGAKQISATSLPTAISAQTPRPPMRRWSSVS
• Function: Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP8 and CASP9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC; Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis; Isoform C is proteolytically inactive.
• Tissue Specificity: Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.
• KEGG Pathway:
  Apoptosis (hsa04210)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  TNF sig.ling pathway (hsa04668)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
• Reactome Pathway:
  FasL/ CD95L signaling (R-HSA-75157)
  TRAIL signaling (R-HSA-75158)
  NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 (R-HSA-933543)
  TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)
• BioCyc Pathway: MetaCyc:HS00093-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune lymphoproliferative syndrome type 2A	DISG0DNJ	Strong	Autosomal dominant	[1]
Autoimmune lymphoproliferative syndrome	DISUG5ES	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Caspase-10 (CASP10) decreases the response to substance of Camptothecin.	[35]

32 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 Caspase-10 (CASP10).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Caspase-10 (CASP10).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Caspase-10 (CASP10).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Caspase-10 (CASP10).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Caspase-10 (CASP10).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Caspase-10 (CASP10).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Caspase-10 (CASP10).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Caspase-10 (CASP10).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Caspase-10 (CASP10).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the activity of Caspase-10 (CASP10).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Caspase-10 (CASP10).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caspase-10 (CASP10).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Caspase-10 (CASP10).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Caspase-10 (CASP10).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Caspase-10 (CASP10).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Caspase-10 (CASP10).	[19]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Caspase-10 (CASP10).	[14]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Caspase-10 (CASP10).	[20]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Caspase-10 (CASP10).	[21]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Caspase-10 (CASP10).	[22]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Caspase-10 (CASP10).	[23]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the activity of Caspase-10 (CASP10).	[24]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone decreases the expression of Caspase-10 (CASP10).	[25]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Caspase-10 (CASP10).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Caspase-10 (CASP10).	[28]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Caspase-10 (CASP10).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Caspase-10 (CASP10).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the activity of Caspase-10 (CASP10).	[12]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Caspase-10 (CASP10).	[31]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Caspase-10 (CASP10).	[32]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A increases the expression of Caspase-10 (CASP10).	[33]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the activity of Caspase-10 (CASP10).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Caspase-10 (CASP10).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Caspase-10 (CASP10).	[27]

References

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