Details of Drug Off-Target (DOT)

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

• DOT Name: IGF-like family receptor 1 (IGFLR1)
• Synonyms: Transmembrane protein 149; U2 small nuclear RNA auxiliary factor 1-like 4
• Gene Name: IGFLR1
• Related Disease: Skin disease
• UniProt ID: IGFR1_HUMAN
• Sequence:
  MGPGRCLLTALLLLALAPPPEASQYCGRLEYWNPDNKCCSSCLQRFGPPPCPDYEFRENC
  GLNDHGDFVTPPFRKCSSGQCNPDGAELCSPCGGGAVTPTPAAGGGRTPWRCRERPVPAK
  GHCPLTPGNPGAPSSQERSSPASSIAWRTPEPVPQQAWPNFLPLVVLVLLLTLAVIAILL
  FILLWHLCWPKEKADPYPYPGLVCGVPNTHTPSSSHLSSPGALETGDTWKEASLLPLLSR
  ELSSLASQPLSRLLDELEVLEELIVLLDPEPGPGGGMAHGTTRHLAARYGLPAAWSTFAY
  SLRPSRSPLRALIEMVVAREPSASLGQLGTHLAQLGRADALRVLSKLGSSGVCWA
• Function: Probable cell membrane receptor for the IGF-like family proteins. Binds IGFL1 and IGFL3 with a higher affinity. May also bind IGFL2.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Skin disease	DISDW8R6	Strong	Biomarker	[1]

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 IGF-like family receptor 1 (IGFLR1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of IGF-like family receptor 1 (IGFLR1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of IGF-like family receptor 1 (IGFLR1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of IGF-like family receptor 1 (IGFLR1).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of IGF-like family receptor 1 (IGFLR1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of IGF-like family receptor 1 (IGFLR1).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of IGF-like family receptor 1 (IGFLR1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of IGF-like family receptor 1 (IGFLR1).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of IGF-like family receptor 1 (IGFLR1).	[10]

References

• [1] Murine insulin growth factor-like (IGFL) and human IGFL1 proteins are induced in inflammatory skin conditions and bind to a novel tumor necrosis factor receptor family member, IGFLR1.J Biol Chem. 2011 May 27;286(21):18969-81. doi: 10.1074/jbc.M111.224626. Epub 2011 Mar 31.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.