Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRYY709)

DOT Name Fatty acyl-CoA reductase 2 (FAR2)
Synonyms EC 1.2.1.84; Male sterility domain-containing protein 1
Gene Name FAR2
Related Disease
Alopecia ( )
Atopic dermatitis ( )
Chronic kidney disease ( )
Diabetic kidney disease ( )
Nephropathy ( )
UniProt ID
FACR2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
1.2.1.84
Pfam ID
PF07993 ; PF03015
Sequence
MSTIAAFYGGKSILITGATGFLGKVLMEKLFRTSPDLKVIYILVRPKAGQTLQQRVFQIL
DSKLFEKVKEVCPNVHEKIRAIYADLNQNDFAISKEDMQELLSCTNIIFHCAATVRFDDT
LRHAVQLNVTATRQLLLMASQMPKLEAFIHISTAYSNCNLKHIDEVIYPCPVEPKKIIDS
LEWLDDAIIDEITPKLIRDWPNIYTYTKALGEMVVQQESRNLNIAIIRPSIVGATWQEPF
PGWVDNINGPNGIIIATGKGFLRAIKATPMAVADVIPVDTVVNLMLAVGWYTAVHRPKST
LVYHITSGNMNPCNWHKMGVQVLATFEKIPFERPFRRPNANFTSNSFTSQYWNAVSHRAP
AIIYDCYLRLTGRKPRMTKLMNRLLRTVSMLEYFINRSWEWSTYNTEMLMSELSPEDQRV
FNFDVRQLNWLEYIENYVLGVKKYLLKEDMAGIPKAKQRLKRLRNIHYLFNTALFLIAWR
LLIARSQMARNVWFFIVSFCYKFLSYFRASSTLKV
Function
Catalyzes the reduction of saturated but not unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols. A lower activity can be observed with shorter fatty acyl-CoA substrates. It may play a role in the production of ether lipids/plasmalogens and wax monoesters which synthesis requires fatty alcohols as substrates.
KEGG Pathway
Peroxisome (hsa04146 )
Reactome Pathway
Wax biosynthesis (R-HSA-9640463 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alopecia DIS37HU4 Strong Biomarker [1]
Atopic dermatitis DISTCP41 Strong Biomarker [2]
Chronic kidney disease DISW82R7 Strong Biomarker [3]
Diabetic kidney disease DISJMWEY Strong Altered Expression [3]
Nephropathy DISXWP4P Strong Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [6]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Fatty acyl-CoA reductase 2 (FAR2). [7]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [7]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [8]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [9]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Fatty acyl-CoA reductase 2 (FAR2). [10]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [11]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [12]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [15]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of Fatty acyl-CoA reductase 2 (FAR2). [16]
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⏷ Show the Full List of 13 Drug(s)
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 increases the methylation of Fatty acyl-CoA reductase 2 (FAR2). [13]
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References

1 Sebaceous gland abnormalities in fatty acyl CoA reductase 2 (Far2) null mice result in primary cicatricial alopecia.PLoS One. 2018 Oct 29;13(10):e0205775. doi: 10.1371/journal.pone.0205775. eCollection 2018.
2 Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.BMC Med Genomics. 2015 Oct 12;8:60. doi: 10.1186/s12920-015-0133-x.
3 FAR2 is associated with kidney disease in mice and humans.Physiol Genomics. 2018 Aug 1;50(8):543-552. doi: 10.1152/physiolgenomics.00118.2017. Epub 2018 Apr 13.
4 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
7 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
8 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9 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.
10 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
11 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.
12 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.
13 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.
14 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.