Details of Drug Off-Target (DOT)

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

• DOT Name: Attractin (ATRN)
• Synonyms: DPPT-L; Mahogany homolog
• Gene Name: ATRN
• Related Disease:
  3-methylglutaconic aciduria type 3
  Barth syndrome
  Cardiomyopathy
  Glioma
  Leukodystrophy
  Neoplasm
  Obesity
  Restless legs syndrome
  Neurodegenerative disease
  Skin cancer
  Squamous cell carcinoma
  Anaplastic astrocytoma
  Astrocytoma
  Asthma
• UniProt ID: ATRN_HUMAN
• Pfam ID: PF00431 ; PF01344 ; PF13964 ; PF01437
• Sequence:
  MVAAAAATEARLRRRTAATAALAGRSGGPHWDWDVTRAGRPGLGAGLRLPRLLSPPLRPR
  LLLLLLLLSPPLLLLLLPCEAEAAAAAAAVSGSAAAEAKECDRPCVNGGRCNPGTGQCVC
  PAGWVGEQCQHCGGRFRLTGSSGFVTDGPGNYKYKTKCTWLIEGQPNRIMRLRFNHFATE
  CSWDHLYVYDGDSIYAPLVAAFSGLIVPERDGNETVPEVVATSGYALLHFFSDAAYNLTG
  FNITYSFDMCPNNCSGRGECKISNSSDTVECECSENWKGEACDIPHCTDNCGFPHRGICN
  SSDVRGCSCFSDWQGPGCSVPVPANQSFWTREEYSNLKLPRASHKAVVNGNIMWVVGGYM
  FNHSDYNMVLAYDLASREWLPLNRSVNNVVVRYGHSLALYKDKIYMYGGKIDSTGNVTNE
  LRVFHIHNESWVLLTPKAKEQYAVVGHSAHIVTLKNGRVVMLVIFGHCPLYGYISNVQEY
  DLDKNTWSILHTQGALVQGGYGHSSVYDHRTRALYVHGGYKAFSANKYRLADDLYRYDVD
  TQMWTILKDSRFFRYLHTAVIVSGTMLVFGGNTHNDTSMSHGAKCFSSDFMAYDIACDRW
  SVLPRPDLHHDVNRFGHSAVLHNSTMYVFGGFNSLLLSDILVFTSEQCDAHRSEAACLAA
  GPGIRCVWNTGSSQCISWALATDEQEEKLKSECFSKRTLDHDRCDQHTDCYSCTANTNDC
  HWCNDHCVPRNHSCSEGQISIFRYENCPKDNPMYYCNKKTSCRSCALDQNCQWEPRNQEC
  IALPENICGIGWHLVGNSCLKITTAKENYDNAKLFCRNHNALLASLTTQKKVEFVLKQLR
  IMQSSQSMSKLTLTPWVGLRKINVSYWCWEDMSPFTNSLLQWMPSEPSDAGFCGILSEPS
  TRGLKAATCINPLNGSVCERPANHSAKQCRTPCALRTACGDCTSGSSECMWCSNMKQCVD
  SNAYVASFPFGQCMEWYTMSTCPPENCSGYCTCSHCLEQPGCGWCTDPSNTGKGKCIEGS
  YKGPVKMPSQAPTGNFYPQPLLNSSMCLEDSRYNWSFIHCPACQCNGHSKCINQSICEKC
  ENLTTGKHCETCISGFYGDPTNGGKCQPCKCNGHASLCNTNTGKCFCTTKGVKGDECQLC
  EVENRYQGNPLRGTCYYTLLIDYQFTFSLSQEDDRYYTAINFVATPDEQNRDLDMFINAS
  KNFNLNITWAASFSAGTQAGEEMPVVSKTNIKEYKDSFSNEKFDFRNHPNITFFVYVSNF
  TWPIKIQIAFSQHSNFMDLVQFFVTFFSCFLSLLLVAAVVWKIKQSCWASRRREQLLREM
  QQMASRPFASVNVALETDEEPPDLIGGSIKTVPKPIALEPCFGNKAAVLSVFVRLPRGLG
  GIPPPGQSGLAVASALVDISQQMPIVYKEKSGAVRNRKQQPPAQPGTCI
• Function: Involved in the initial immune cell clustering during inflammatory response and may regulate chemotactic activity of chemokines. May play a role in melanocortin signaling pathways that regulate energy homeostasis and hair color. Low-affinity receptor for agouti. Has a critical role in normal myelination in the central nervous system.
• Tissue Specificity: Isoform 2 is detected in plasma (at protein level). Expressed and secreted by activated T-lymphocytes. Expressed at low to moderate levels in peripheral blood leukocytes, spleen, lymph node, tonsil, bone marrow and fetal liver. At very low levels found in thymus. Isoform 2 is the major isoform in peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3-methylglutaconic aciduria type 3	DISDQMDY	Strong	Genetic Variation	[1]
Barth syndrome	DISDI4KU	Strong	Biomarker	[2]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Leukodystrophy	DISVY1TT	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Restless legs syndrome	DISNWY00	Strong	Biomarker	[6]
Neurodegenerative disease	DISM20FF	moderate	Biomarker	[7]
Skin cancer	DISTM18U	moderate	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[8]
Anaplastic astrocytoma	DISSBE0K	Disputed	Biomarker	[3]
Astrocytoma	DISL3V18	Disputed	Altered Expression	[3]
Asthma	DISW9QNS	Limited	Genetic Variation	[9]

6 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 Attractin (ATRN).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Attractin (ATRN).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Attractin (ATRN).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Attractin (ATRN).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Attractin (ATRN).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Attractin (ATRN).	[15]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Attractin (ATRN).	[16]

References

• [1] OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria.Mol Genet Metab. 2010 Jun;100(2):149-54. doi: 10.1016/j.ymgme.2010.03.005. Epub 2010 Mar 16.
• [2] Barth syndrome.Orphanet J Rare Dis. 2013 Feb 12;8:23. doi: 10.1186/1750-1172-8-23.
• [3] Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration.Clin Cancer Res. 2006 Nov 1;12(21):6331-6. doi: 10.1158/1078-0432.CCR-06-1296.
• [4] Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN gene.Neurogenetics. 2017 Jul;18(3):135-139. doi: 10.1007/s10048-017-0515-7. Epub 2017 May 10.
• [5] Attractin: cautionary tales for therapeutic intervention in molecules with pleiotropic functionality.J Environ Pathol Toxicol Oncol. 2004;23(1):1-11. doi: 10.1615/jenvpathtoxoncol.v23.i1.10.
• [6] Exome sequencing in a family with restless legs syndrome.Mov Disord. 2012 Nov;27(13):1686-9. doi: 10.1002/mds.25191.
• [7] The neuroprotective role of attractin in neurodegeneration.Neurobiol Aging. 2007 Sep;28(9):1446-56. doi: 10.1016/j.neurobiolaging.2006.06.014. Epub 2006 Jul 24.
• [8] Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.Int J Cancer. 2009 Aug 15;125(4):909-17. doi: 10.1002/ijc.24327.
• [9] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [10] 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.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [13] 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.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] 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.