Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBNYF3F)

DOT Name ADAMTS-like protein 1 (ADAMTSL1)
Synonyms ADAMTSL-1; Punctin-1
Gene Name ADAMTSL1
Related Disease
Alcohol dependence ( )
Autosomal dominant prognathism ( )
Cardiac failure ( )
Chondrosarcoma ( )
Congenital glaucoma ( )
Glaucoma/ocular hypertension ( )
Parkinson disease ( )
Asthma ( )
Myopia ( )
Small-cell lung cancer ( )
UniProt ID
ATL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF19236 ; PF05986 ; PF07679 ; PF13927 ; PF08686 ; PF19030 ; PF00090
Sequence
MECCRRATPGTLLLFLAFLLLSSRTARSEEDRDGLWDAWGPWSECSRTCGGGASYSLRRC
LSSKSCEGRNIRYRTCSNVDCPPEAGDFRAQQCSAHNDVKHHGQFYEWLPVSNDPDNPCS
LKCQAKGTTLVVELAPKVLDGTRCYTESLDMCISGLCQIVGCDHQLGSTVKEDNCGVCNG
DGSTCRLVRGQYKSQLSATKSDDTVVAIPYGSRHIRLVLKGPDHLYLETKTLQGTKGENS
LSSTGTFLVDNSSVDFQKFPDKEILRMAGPLTADFIVKIRNSGSADSTVQFIFYQPIIHR
WRETDFFPCSATCGGGYQLTSAECYDLRSNRVVADQYCHYYPENIKPKPKLQECNLDPCP
ASDGYKQIMPYDLYHPLPRWEATPWTACSSSCGGGIQSRAVSCVEEDIQGHVTSVEEWKC
MYTPKMPIAQPCNIFDCPKWLAQEWSPCTVTCGQGLRYRVVLCIDHRGMHTGGCSPKTKP
HIKEECIVPTPCYKPKEKLPVEAKLPWFKQAQELEEGAAVSEEPSFIPEAWSACTVTCGV
GTQVRIVRCQVLLSFSQSVADLPIDECEGPKPASQRACYAGPCSGEIPEFNPDETDGLFG
GLQDFDELYDWEYEGFTKCSESCGGGVQEAVVSCLNKQTREPAEENLCVTSRRPPQLLKS
CNLDPCPARWEIGKWSPCSLTCGVGLQTRDVFCSHLLSREMNETVILADELCRQPKPSTV
QACNRFNCPPAWYPAQWQPCSRTCGGGVQKREVLCKQRMADGSFLELPETFCSASKPACQ
QACKKDDCPSEWLLSDWTECSTSCGEGTQTRSAICRKMLKTGLSTVVNSTLCPPLPFSSS
IRPCMLATCARPGRPSTKHSPHIAAARKVYIQTRRQRKLHFVVGGFAYLLPKTAVVLRCP
ARRVRKPLITWEKDGQHLISSTHVTVAPFGYLKIHRLKPSDAGVYTCSAGPAREHFVIKL
IGGNRKLVARPLSPRSEEEVLAGRKGGPKEALQTHKHQNGIFSNGSKAEKRGLAANPGSR
YDDLVSRLLEQGGWPGELLASWEAQDSAERNTTSEEDPGAEQVLLHLPFTMVTEQRRLDD
ILGNLSQQPEELRDLYSKHLVAQLAQEIFRSHLEHQDTLLKPSERRTSPVTLSPHKHVSG
FSSSLRTSSTGDAGGGSRRPHRKPTILRKISAAQQLSASEVVTHLGQTVALASGTLSVLL
HCEAIGHPRPTISWARNGEEVQFSDRILLQPDDSLQILAPVEADVGFYTCNATNALGYDS
VSIAVTLAGKPLVKTSRMTVINTEKPAVTVDIGSTIKTVQGVNVTINCQVAGVPEAEVTW
FRNKSKLGSPHHLHEGSLLLTNVSSSDQGLYSCRAANLHGELTESTQLLILDPPQVPTQL
EDIRALLAATGPNLPSVLTSPLGTQLVLDPGNSALLGCPIKGHPVPNITWFHGGQPIVTA
TGLTHHILAAGQILQVANLSGGSQGEFSCLAQNEAGVLMQKASLVIQDYWWSVDRLATCS
ASCGNRGVQQPRLRCLLNSTEVNPAHCAGKVRPAVQPIACNRRDCPSRWMVTSWSACTRS
CGGGVQTRRVTCQKLKASGISTPVSNDMCTQVAKRPVDTQACNQQLCVEWAFSSWGQCNG
PCIGPHLAVQHRQVFCQTRDGITLPSEQCSALPRPVSTQNCWSEACSVHWRVSLWTLCTA
TCGNYGFQSRRVECVHARTNKAVPEHLCSWGPRPANWQRCNITPCENMECRDTTRYCEKV
KQLKLCQLSQFKSRCCGTCGKA
Tissue Specificity Expressed primarily in adult skeletal muscle.
Reactome Pathway
O-glycosylation of TSR domain-containing proteins (R-HSA-5173214 )
Defective B3GALTL causes PpS (R-HSA-5083635 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcohol dependence DIS4ZSCO Strong Genetic Variation [1]
Autosomal dominant prognathism DIS2G3FF Strong Genetic Variation [2]
Cardiac failure DISDC067 Strong Genetic Variation [3]
Chondrosarcoma DIS4I7JB Strong Altered Expression [4]
Congenital glaucoma DISHN3GO Strong Genetic Variation [5]
Glaucoma/ocular hypertension DISLBXBY Strong Genetic Variation [6]
Parkinson disease DISQVHKL Strong Genetic Variation [7]
Asthma DISW9QNS Limited Genetic Variation [8]
Myopia DISK5S60 Limited Genetic Variation [9]
Small-cell lung cancer DISK3LZD Limited Genetic Variation [10]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 ADAMTS-like protein 1 (ADAMTSL1). [11]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of ADAMTS-like protein 1 (ADAMTSL1). [14]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of ADAMTS-like protein 1 (ADAMTSL1). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of ADAMTS-like protein 1 (ADAMTSL1). [16]
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7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of ADAMTS-like protein 1 (ADAMTSL1). [12]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of ADAMTS-like protein 1 (ADAMTSL1). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of ADAMTS-like protein 1 (ADAMTSL1). [15]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of ADAMTS-like protein 1 (ADAMTSL1). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of ADAMTS-like protein 1 (ADAMTSL1). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of ADAMTS-like protein 1 (ADAMTSL1). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of ADAMTS-like protein 1 (ADAMTSL1). [20]
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⏷ Show the Full List of 7 Drug(s)

References

1 A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.Mol Psychiatry. 2013 Nov;18(11):1218-24. doi: 10.1038/mp.2012.143. Epub 2012 Oct 23.
2 ADAMTSL1 and mandibular prognathism.Clin Genet. 2019 Apr;95(4):507-515. doi: 10.1111/cge.13519.
3 Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.Circ Cardiovasc Genet. 2010 Jun;3(3):256-66. doi: 10.1161/CIRCGENETICS.109.895763. Epub 2010 May 5.
4 Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth.Mol Cancer Ther. 2014 May;13(5):1259-69. doi: 10.1158/1535-7163.MCT-13-0731. Epub 2014 Mar 14.
5 Identification and functional analysis of an ADAMTSL1 variant associated with a complex phenotype including congenital glaucoma, craniofacial, and other systemic features in a three-generation human pedigree.Hum Mutat. 2017 Nov;38(11):1485-1490. doi: 10.1002/humu.23299. Epub 2017 Aug 1.
6 Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1.Nat Genet. 2011 Jun;43(6):574-8. doi: 10.1038/ng.824. Epub 2011 May 1.
7 Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data.Lancet Neurol. 2006 Nov;5(11):911-6. doi: 10.1016/S1474-4422(06)70578-6.
8 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.
9 Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
10 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
11 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.
12 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
13 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
14 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
15 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
16 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
17 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.
18 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
19 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.
20 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.