Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3X4HCS)

• DOT Name: Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1)
• Synonyms: PPEF-1; EC 3.1.3.16; Protein phosphatase with EF calcium-binding domain; PPEF; Serine/threonine-protein phosphatase 7; PP7
• Gene Name: PPEF1
• UniProt ID: PPE1_HUMAN
• EC Number: 3.1.3.16
• Pfam ID: PF13499 ; PF00612 ; PF00149 ; PF08321
• Sequence:
  MGCSSSSTKTRRSDTSLRAALIIQNWYRGYKARLKARQHYALTIFQSIEYADEQGQMQLS
  TFFSFMLENYTHIHKEELELRNQSLESEQDMRDRWDYVDSIDVPDSYNGPRLQFPLTCTD
  IDLLLEAFKEQQILHAHYVLEVLFETKKVLKQMPNFTHIQTSPSKEVTICGDLHGKLDDL
  FLIFYKNGLPSERNPYVFNGDFVDRGKNSIEILMILCVSFLVYPNDLHLNRGNHEDFMMN
  LRYGFTKEILHKYKLHGKRILQILEEFYAWLPIGTIVDNEILVIHGGISETTDLNLLHRV
  ERNKMKSVLIPPTETNRDHDTDSKHNKVGVTFNAHGRIKTNGSPTEHLTEHEWEQIIDIL
  WSDPRGKNGCFPNTCRGGGCYFGPDVTSKILNKYQLKMLIRSHECKPEGYEICHDGKVVT
  IFSASNYYEEGSNRGAYIKLCSGTTPRFFQYQVTKATCFQPLRQRVDTMENSAIKILRER
  VISRKSDLTRAFQLQDHRKSGKLSVSQWAFCMENILGLNLPWRSLSSNLVNIDQNGNVEY
  MSSFQNIRIEKPVQEAHSTLVETLYRYRSDLEIIFNAIDTDHSGLISVEEFRAMWKLFSS
  HYNVHIDDSQVNKLANIMDLNKDGSIDFNEFLKAFYVVHRYEDLMKPDVTNLG
• Function: May have a role in the recovery or adaptation response of photoreceptors. May have a role in development.
• Tissue Specificity: Detected in retina and retinal derived Y-79 retinoblastoma cells. Also found in fetal brain.
• Reactome Pathway: Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[1]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[2]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein phosphatase with EF-hands 1 (PPEF1).	[7]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [3] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [4] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [5] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [6] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.