Details of Drug Off-Target (DOT)

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

• DOT Name: Microfibrillar-associated protein 3-like (MFAP3L)
• Synonyms: Testis development protein NYD-SP9
• Gene Name: MFAP3L
• Related Disease:
  Anxiety disorder
  Colorectal carcinoma
• UniProt ID: MFA3L_HUMAN
• Pfam ID: PF07679
• Sequence:
  MDRLKSHLTVCFLPSVPFLILVSTLATAKSVTNSTLNGTNVVLGSVPVIIARTDHIIVKE
  GNSALINCSVYGIPDPQFKWYNSIGKLLKEEEDEKERGGGKWQMHDSGLLNITKVSFSDR
  GKYTCVASNIYGTVNNTVTLRVIFTSGDMGVYYMVVCLVAFTIVMVLNITRLCMMSSHLK
  KTEKAINEFFRTEGAEKLQKAFEIAKRIPIITSAKTLELAKVTQFKTMEFARYIEELARS
  VPLPPLIMNCRTIMEEIMEVVGLEEQGQNFVRHTPEGQEAADRDEVYTIPNSLKRSDSPA
  ADSDASSLHEQPQQIAIKVSVHPQSKKEHADDQEGGQFEVKDVEETELSAEHSPETAEPS
  TDVTSTELTSEEPTPVEVPDKVLPPAYLEATEPAVTHDKNTCIIYESHV
• Function: May participate in the nuclear signaling of EGFR and MAPK1/ERK2. May a have a role in metastasis.
• Tissue Specificity: Highly expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]

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 Microfibrillar-associated protein 3-like (MFAP3L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microfibrillar-associated protein 3-like (MFAP3L).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[8]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Microfibrillar-associated protein 3-like (MFAP3L).	[14]

References

• [1] Genome-wide and gene-based association studies of anxiety disorders in European and African American samples.PLoS One. 2014 Nov 12;9(11):e112559. doi: 10.1371/journal.pone.0112559. eCollection 2014.
• [2] MFAP3L activation promotes colorectal cancer cell invasion and metastasis.Biochim Biophys Acta. 2014 Sep;1842(9):1423-32. doi: 10.1016/j.bbadis.2014.04.006. Epub 2014 Apr 13.
• [3] 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.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [7] 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.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [10] 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.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.