Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0YTMN2)

• DOT Name: Complexin-3 (CPLX3)
• Synonyms: Complexin III; CPX III
• Gene Name: CPLX3
• UniProt ID: CPLX3_HUMAN
• Pfam ID: PF05835
• Sequence:
  MAFMVKTMVGGQLKNLTGSLGGGEDKGDGDKSAAEAQGMSREEYEEYQKQLVEEKMERDA
  QFTQRKAERATLRSHFRDKYRLPKNETDESQIQMAGGDVELPRELAKMIEEDTEEEEEKA
  SVLGQLASLPGLNLGSLKDKAQATLGDLKQSAEKCHVM
• Function: Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion. Required for the maintenance of synaptic ultrastructure in the adult retina. Positively regulates synaptic transmission through synaptic vesicle availability and exocytosis of neurotransmitters at photoreceptor ribbon synapses in the retina. Suppresses tonic photoreceptor activity and baseline 'noise' by suppression of Ca(2+) vesicle tonic release and the facilitation of evoked synchronous and asynchronous Ca(2+) vesicle release.
• KEGG Pathway: Sy.ptic vesicle cycle (hsa04721)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Complexin-3 (CPLX3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Complexin-3 (CPLX3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Complexin-3 (CPLX3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Complexin-3 (CPLX3).	[3]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Complexin-3 (CPLX3).	[4]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Complexin-3 (CPLX3).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Complexin-3 (CPLX3).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [5] Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres. Int J Mol Sci. 2020 Aug 3;21(15):5564. doi: 10.3390/ijms21155564.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.