Details of Drug Off-Target (DOT)

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

• DOT Name: Actin maturation protease (ACTMAP)
• Synonyms: EC 3.4.11.-; Actin aminopeptidase ACTMAP
• Gene Name: ACTMAP
• UniProt ID: ACTMP_HUMAN
• EC Number: 3.4.11.-
• Pfam ID: PF21646
• Sequence:
  MTSPCSPPLKPPISPPKTPVPQASSIPSPPLPPSPLDFSALPSPPWSQQTPVPPPLPLPP
  PPAATGPAPRHVFGLEKSQLLKEAFDKAGPVPKGREDVKRLLKLHKDRFRGDLRWILFCA
  DLPSLIQEGPQCGLVALWMAGTLLSPPSGVPLERLIRVATERGYTAQGEMFSVADMGRLA
  QEVLGCQAKLLSGGLGGPNRDLVLQHLVTGHPLLIPYDEDFNHEPCQRKGHKAHWAVSAG
  VLLGVRAVPSLGYTEDPELPGLFHPVLGTPCQPPSLPEEGSPGAVYLLSKQGKSWHYQLW
  DYDQVRESNLQLTDFSPSRATDGRVYVVPVGGVRAGLCGQALLLTPQDCSH
• Function: Actin maturation protease that specifically mediates the cleavage of immature acetylated N-terminal actin, thereby contributing to actin maturation. Cleaves N-terminal acetylated methionine of immature cytoplasmic beta- and gamma-actins ACTB and ACTG1 after translation. Cleaves N-terminal acetylated cysteine of muscle alpha-actins ACTA1, ACTC1 and ACTA2 after canonical removal of N-terminal methionine.

Molecular Interaction Atlas (MIA) of This DOT

4 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 Actin maturation protease (ACTMAP).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Actin maturation protease (ACTMAP).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Actin maturation protease (ACTMAP).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Actin maturation protease (ACTMAP).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Actin maturation protease (ACTMAP).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Actin maturation protease (ACTMAP).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Actin maturation protease (ACTMAP).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Actin maturation protease (ACTMAP).	[8]

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] 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.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.