Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7GN95)

DOT Name	Chronophin (PDXP)
Synonyms	EC 3.1.3.16; EC 3.1.3.74; Pyridoxal phosphate phosphatase; PLP phosphatase
Gene Name	PDXP
UniProt ID	PLPP_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2CFR; 2CFS; 2CFT; 2OYC; 2P27; 2P69; 5GYN
EC Number	3.1.3.16; 3.1.3.74
Pfam ID	PF13344 ; PF13242
Sequence	MARCERLRGAALRDVLGRAQGVLFDCDGVLWNGERAVPGAPELLERLARAGKAALFVSNN SRRARPELALRFARLGFGGLRAEQLFSSALCAARLLRQRLPGPPDAPGAVFVLGGEGLRA ELRAAGLRLAGDPSAGDGAAPRVRAVLVGYDEHFSFAKLREACAHLRDPECLLVATDRDP WHPLSDGSRTPGTGSLAAAVETASGRQALVVGKPSPYMFECITENFSIDPARTLMVGDRL ETDILFGHRCGMTTVLTLTGVSRLEEAQAYLAAGQHDLVPHYYVESIADLTEGLED
Function	Functions as a pyridoxal phosphate (PLP) phosphatase, which also catalyzes the dephosphorylation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), with order of substrate preference PLP > PNP > PMP and therefore plays a role in vitamin B6 metabolism. Also functions as a protein serine phosphatase that specifically dephosphorylates 'Ser-3' in proteins of the actin-depolymerizing factor (ADF)/cofilin family like CFL1 and DSTN. Thereby, regulates cofilin-dependent actin cytoskeleton reorganization, being required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phosphothreonines in LIMK1. Does not dephosphorylate peptides containing phosphotyrosine.
Tissue Specificity	Ubiquitously expressed (at protein level) . Highly expressed in all the regions of central nerve system except the spinal cord. Also expressed at high level in liver and testis. In fetus, it is weakly expressed in all organs except brain .
KEGG Pathway	Vitamin B6 metabolism (hsa00750 ) Metabolic pathways (hsa01100 ) Biosynthesis of cofactors (hsa01240 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Chronophin (PDXP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chronophin (PDXP).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Chronophin (PDXP).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chronophin (PDXP).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Chronophin (PDXP).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Chronophin (PDXP).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Chronophin (PDXP).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chronophin (PDXP).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chronophin (PDXP).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Chronophin (PDXP).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Chronophin (PDXP).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Chronophin (PDXP).	[12]
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⏷ Show the Full List of 12 Drug(s)

References

1	Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
2	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
4	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
5	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
6	Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
7	Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
8	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
9	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
10	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
11	Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
12	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.