Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4QK8O)

DOT Name	Kallikrein-4 (KLK4)
Synonyms	EC 3.4.21.-; Enamel matrix serine proteinase 1; Kallikrein-like protein 1; KLK-L1; Prostase; Serine protease 17
Gene Name	KLK4
Related Disease	Amelogenesis imperfecta type 2A1 ( ) Amelogenesis imperfecta type 2 ( )
UniProt ID	KLK4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2BDG; 2BDH; 2BDI; 4K1E; 4K8Y; 4KEL; 4KGA; 6KBR; 6NVB; 6O21; 7JOD; 7JOE; 7JOS; 7JOW; 7JQK; 7JQN; 7JQO; 7JQV
EC Number	3.4.21.-
Pfam ID	PF00089
Sequence	MATAGNPWGWFLGYLILGVAGSLVSGSCSQIINGEDCSPHSQPWQAALVMENELFCSGVL VHPQWVLSAAHCFQNSYTIGLGLHSLEADQEPGSQMVEASLSVRHPEYNRPLLANDLMLI KLDESVSESDTIRSISIASQCPTAGNSCLVSGWGLLANGRMPTVLQCVNVSVVSEEVCSK LYDPLYHPSMFCAGGGHDQKDSCNGDSGGPLICNGYLQGLVSFGKAPCGQVGVPGVYTNL CKFTEWIEKTVQAS
Function	Has a major role in enamel formation. Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix.
Tissue Specificity	Expressed in prostate.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Amelogenesis imperfecta type 2A1	DISTCV2U	Strong	Autosomal recessive	[1]
Amelogenesis imperfecta type 2	DISX8NN4	Supportive	Autosomal recessive	[2]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Kallikrein-4 (KLK4) affects the response to substance of Cisplatin.	[6]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Kallikrein-4 (KLK4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kallikrein-4 (KLK4).	[5]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Kallikrein-4 (KLK4).	[4]
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References

1	Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet. 2004 Jul;41(7):545-9. doi: 10.1136/jmg.2003.017657.
2	Amelogenesis imperfecta: genotype-phenotype studies in 71 families. Cells Tissues Organs. 2011;194(2-4):279-83. doi: 10.1159/000324339. Epub 2011 May 19.
3	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
4	LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
5	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.
6	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.