Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTILMO80)

• DOT Name: Kallikrein-14 (KLK14)
• Synonyms: hK14; EC 3.4.21.-; Kallikrein-like protein 6; KLK-L6
• Gene Name: KLK14
• UniProt ID: KLK14_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MSLRVLGSGTWPSAPKMFLLLTALQVLAIAMTQSQEDENKIIGGHTCTRSSQPWQAALLA
  GPRRRFLCGGALLSGQWVITAAHCGRPILQVALGKHNLRRWEATQQVLRVVRQVTHPNYN
  SRTHDNDLMLLQLQQPARIGRAVRPIEVTQACASPGTSCRVSGWGTISSPIARYPASLQC
  VNINISPDEVCQKAYPRTITPGMVCAGVPQGGKDSCQGDSGGPLVCRGQLQGLVSWGMER
  CALPGYPGVYTNLCKYRSWIEETMRDK
• Function: Serine-type endopeptidase with a dual trypsin-like and chymotrypsin-like substrate specificity. May activate/inactivate the proteinase-activated receptors F2R, F2RL1 and F2RL3 and other kallikreins including KLK1, KLK3, KLK5 and KLK11. May function in seminal clot liquefaction through direct cleavage of the semenogelin SEMG1 and SEMG2 and activation of KLK3. May function through desmoglein DSG1 cleavage in epidermal desquamation a process by which the most superficial corneocytes are shed from the skin surface. May be involved in several aspects of tumor progression including growth, invasion and angiogenesis.
• Tissue Specificity: Highly expressed in CNS, bone marrow and fetal liver. Also expressed in breast, thyroid, kidney, colon, pancreas, spleen, prostate, uterus, small intestine, placenta and skeletal muscle. Among 40 tissues tested, the highest expression is detected in skin followed by breast and prostate (at protein level). Expressed in stratum corneum by sweat ducts and sweat glands and detected in sweat (at protein level).
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Kallikrein-14 (KLK14).	[1]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kallikrein-14 (KLK14).	[3]

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 affects the methylation of Kallikrein-14 (KLK14).	[2]

References

• [1] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [2] 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.
• [3] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.