Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWKW0Y6)

• DOT Name: Calpain-14 (CAPN14)
• Synonyms: EC 3.4.22.-; Calcium-activated neutral proteinase 14; CANP 14
• Gene Name: CAPN14
• Related Disease:
  Acute otitis media
  Gastroesophageal reflux disease
  Otitis media
  Endometriosis
  Eosinophilic esophagitis
• UniProt ID: CAN14_HUMAN
• EC Number: 3.4.22.-
• Pfam ID: PF01067 ; PF00648
• Sequence:
  MSLWPPFRCRWKLAPRYSRRASPQQPQQDFEALLAECLRNGCLFEDTSFPATLSSIGSGS
  LLQKLPPRLQWKRPPELHSNPQFYFAKAKRLDLCQGIVGDCWFLAALQALALHQDILSRV
  VPLNQSFTEKYAGIFRFWFWHYGNWVPVVIDDRLPVNEAGQLVFVSSTYKNLFWGALLEK
  AYAKLSGSYEDLQSGQVSEALVDFTGGVTMTINLAEAHGNLWDILIEATYNRTLIGCQTH
  SGEKILENGLVEGHAYTLTGIRKVTCKHRPEYLVKLRNPWGKVEWKGDWSDSSSKWELLS
  PKEKILLLRKDNDGEFWMTLQDFKTHFVLLVICKLTPGLLSQEAAQKWTYTMREGRWEKR
  STAGGQRQLLQDTFWKNPQFLLSVWRPEEGRRSLRPCSVLVSLLQKPRHRCRKRKPLLAI
  GFYLYRMNKYHDDQRRLPPEFFQRNTPLSQPDRFLKEKEVSQELCLEPGTYLIVPCILEA
  HQKSEFVLRVFSRKHIFYEIGSNSGVVFSKEIEDQNERQDEFFTKFFEKHPEINAVQLQN
  LLNQMTWSSLGSRQPFFSLEACQGILALLDLNASGTMSIQEFRDLWKQLKLSQKVFHKQD
  RGSGYLNWEQLHAAMREAGIMLSDDVCQLMLIRYGGPRLQMDFVSFIHLMLRVENMEDVF
  QNLTQDGKGIYLQKPEWMMMALYS
• Function: Calcium-regulated non-lysosomal thiol-protease.
• Tissue Specificity: Not expressed in tissues tested.
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute otitis media	DISL8D8G	Strong	Biomarker	[1]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Altered Expression	[2]
Otitis media	DISGZDUO	Strong	Biomarker	[1]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[3]
Eosinophilic esophagitis	DISR8WSB	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Calpain-14 (CAPN14).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calpain-14 (CAPN14).	[7]

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 Calpain-14 (CAPN14).	[6]

References

• [1] Genome-wide association study to identify the genetic determinants of otitis media susceptibility in childhood.PLoS One. 2012;7(10):e48215. doi: 10.1371/journal.pone.0048215. Epub 2012 Oct 25.
• [2] Pathophysiology of Eosinophilic Esophagitis.Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.
• [3] Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.Hum Reprod. 2017 Apr 1;32(4):780-793. doi: 10.1093/humrep/dex024.
• [4] Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications.Clin Rev Allergy Immunol. 2019 Aug;57(1):111-127. doi: 10.1007/s12016-019-08733-0.
• [5] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.