Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7D6VLN)

• DOT Name: Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1)
• Synonyms: Synaptic adhesion-like molecule 2
• Gene Name: LRFN1
• UniProt ID: LRFN1_HUMAN
• Pfam ID: PF00041 ; PF07679 ; PF13855
• Sequence:
  MAPGPFSSALLSPPPAALPFLLLLWAGASRGQPCPGRCICQNVAPTLTMLCAKTGLLFVP
  PAIDRRVVELRLTDNFIAAVRRRDFANMTSLVHLTLSRNTIGQVAAGAFADLRALRALHL
  DSNRLAEVRGDQLRGLGNLRHLILGNNQIRRVESAAFDAFLSTVEDLDLSYNNLEALPWE
  AVGQMVNLNTLTLDHNLIDHIAEGTFVQLHKLVRLDMTSNRLHKLPPDGLFLRSQGTGPK
  PPTPLTVSFGGNPLHCNCELLWLRRLTREDDLETCATPEHLTDRYFWSIPEEEFLCEPPL
  ITRQAGGRALVVEGQAVSLRCRAVGDPEPVVHWVAPDGRLLGNSSRTRVRGDGTLDVTIT
  TLRDSGTFTCIASNAAGEATAPVEVCVVPLPLMAPPPAAPPPLTEPGSSDIATPGRPGAN
  DSAAERRLVAAELTSNSVLIRWPAQRPVPGIRMYQVQYNSSVDDSLVYRMIPSTSQTFLV
  NDLAAGRAYDLCVLAVYDDGATALPATRVVGCVQFTTAGDPAPCRPLRAHFLGGTMIIAI
  GGVIVASVLVFIVLLMIRYKVYGDGDSRRVKGSRSLPRVSHVCSQTNGAGTGAAQAPALP
  AQDHYEALREVESQAAPAVAVEAKAMEAETASAEPEVVLGRSLGGSATSLCLLPSEETSG
  EESRAAVGPRRSRSGALEPPTSAPPTLALVPGGAAARPRPQQRYSFDGDYGALFQSHSYP
  RRARRTKRHRSTPHLDGAGGGAAGEDGDLGLGSARACLAFTSTEWMLESTV
• Function: Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1.
• Reactome Pathway: Synaptic adhesion-like molecules (R-HSA-8849932)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[8]

1 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 decreases the methylation of Leucine-rich repeat and fibronectin type III domain-containing protein 1 (LRFN1).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] 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.
• [8] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.