Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKW8PXG)

• DOT Name: N-terminal EF-hand calcium-binding protein 1 (NECAB1)
• Synonyms: EF-hand calcium-binding protein 1; Neuronal calcium-binding protein 1
• Gene Name: NECAB1
• UniProt ID: NECA1_HUMAN
• Pfam ID: PF03992
• Sequence:
  MEDSQETSPSSNNSSEELSSALHLSKGMSIFLDILRRADKNDDGKLSFEEFKAYFADGVL
  SGEELHELFHTIDTHNTNNLDTEELCEYFSQHLGEYENVLAALEDLNLSILKAMGKTKKD
  YQEASNLEQFVTRFLLKETLNQLQSLQNSLECAMETTEEQTRQERQGPAKPEVLSIQWPG
  KRSSRRVQRHNSFSPNSPQFNVSGPGLLEEDNQWMTQINRLQKLIDRLEKKDLKLEPPEE
  EIIEGNTKSHIMLVQRQMSVIEEDLEEFQLALKHYVESASSQSGCLRISIQKLSNESRYM
  IYEFWENSSVWNSHLQTNYSKTFQRSNVDFLETPELTSTMLVPASWWILNN
• Tissue Specificity: Expressed in brain (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[4]

2 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 increases the methylation of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of N-terminal EF-hand calcium-binding protein 1 (NECAB1).	[6]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.