Details of Drug Off-Target (DOT)

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

• DOT Name: Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1)
• Synonyms: EC 3.4.17.17; Microtubule-associated tyrosine carboxypeptidase
• Gene Name: MATCAP1
• UniProt ID: MACA1_HUMAN
• PDB ID: 7Z5G; 7Z5H; 7Z6S
• EC Number: 3.4.17.17
• Pfam ID: PF08014
• Sequence:
  MVLDSGAQAYDQAPPSPPTSPPSLRHRLKPSDRDGPPLYPWSQSLALPLALAVPPALQPQ
  PEQQPFSQMLLGHRGHMRRSESTYSVNSTGRRGRGTLGRPPPGRGRNPGGGTLRPAASLP
  HIAKTQRDAGHIASKSPCMLVALRPTNMDRERDKFFQSHYTYNPQFEYQEPMPTAVLEKY
  CEASGQFIHQAVGIIEAVLEKFGTYEHFEAATGGQLLTKCQIWSIVRKYMQKEGCAGEVV
  VQLSEDLLSQAVMMVENSRPTLAINLTGARQYWLEGMLRHEIGTHYLRGVNNARQPWHNA
  EGRLRYGLRPANPTEEGLASLHSVLFRKQPFLWRAALLYYTIHRAARMSFRQLFQDLERY
  VQDADVRWEYCVRAKRGQTDTSLPGCFSKDQVYLDGIVRILRHRQTIDFPLLTSLGKVSY
  EDVDHLRPHGVLDNTRVPHFMQDLARYRQQLEHIMATNRLDEAELGRLLPD
• Function: Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function. Also able to remove the C-terminal phenylalanine residue of alpha-tubulin TUBA8. Recognizes adjacent tubulin dimers along the same protofilament.

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 Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Microtubule-associated tyrosine carboxypeptidase 1 (MATCAP1).	[6]

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] 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.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] 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.
• [5] 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.
• [6] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.