Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAXNV2U)

DOT Name ADAMTS-like protein 2 (ADAMTSL2)
Synonyms ADAMTSL-2
Gene Name ADAMTSL2
Related Disease
Acromicric dysplasia ( )
Geleophysic dysplasia 1 ( )
Heart valve disorder ( )
Hyperostosis corticalis generalisata ( )
Inborn error of metabolism ( )
Isolated ectopia lentis ( )
Melnick-Needles syndrome ( )
Multiple epiphyseal dysplasia ( )
Osteochondrodysplasia ( )
Schwartz-Jampel syndrome ( )
Schwartz-Jampel syndrome type 1 ( )
Spondyloepiphyseal dysplasia ( )
Spondyloepiphyseal dysplasia tarda, X-linked ( )
Geleophysic dysplasia ( )
Ehlers-Danlos syndrome ( )
UniProt ID
ATL2_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 ; PF08686 ; PF19030 ; PF00090
Sequence
MDGRWQCSCWAWFLLVLAVVAGDTVSTGSTDNSPTSNSLEGGTDATAFWWGEWTKWTACS
RSCGGGVTSQERHCLQQRRKSVPGPGNRTCTGTSKRYQLCRVQECPPDGRSFREEQCVSF
NSHVYNGRTHQWKPLYPDDYVHISSKPCDLHCTTVDGQRQLMVPARDGTSCKLTDLRGVC
VSGKCEPIGCDGVLFSTHTLDKCGICQGDGSSCTHVTGNYRKGNAHLGYSLVTHIPAGAR
DIQIVERKKSADVLALADEAGYYFFNGNYKVDSPKNFNIAGTVVKYRRPMDVYETGIEYI
VAQGPTNQGLNVMVWNQNGKSPSITFEYTLLQPPHESRPQPIYYGFSESAESQGLDGAGL
MGFVPHNGSLYGQASSERLGLDNRLFGHPGLDMELGPSQGQETNEVCEQAGGGACEGPPR
GKGFRDRNVTGTPLTGDKDDEEVDTHFASQEFFSANAISDQLLGAGSDLKDFTLNETVNS
IFAQGAPRSSLAESFFVDYEENEGAGPYLLNGSYLELSSDRVANSSSEAPFPNVSTSLLT
SAGNRTHKARTRPKARKQGVSPADMYRWKLSSHEPCSATCTTGVMSAYAMCVRYDGVEVD
DSYCDALTRPEPVHEFCAGRECQPRWETSSWSECSRTCGEGYQFRVVRCWKMLSPGFDSS
VYSDLCEAAEAVRPEERKTCRNPACGPQWEMSEWSECTAKCGERSVVTRDIRCSEDEKLC
DPNTRPVGEKNCTGPPCDRQWTVSDWGPCSGSCGQGRTIRHVYCKTSDGRVVPESQCQME
TKPLAIHPCGDKNCPAHWLAQDWERCNTTCGRGVKKRLVLCMELANGKPQTRSGPECGLA
KKPPEESTCFERPCFKWYTSPWSECTKTCGVGVRMRDVKCYQGTDIVRGCDPLVKPVGRQ
ACDLQPCPTEPPDDSCQDQPGTNCALAIKVNLCGHWYYSKACCRSCRPPHS
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

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acromicric dysplasia DISMV8M7 Strong Biomarker [1]
Geleophysic dysplasia 1 DIS4P7XS Strong Autosomal recessive [2]
Heart valve disorder DIS84O7T Strong Biomarker [3]
Hyperostosis corticalis generalisata DISR4BHB Strong Biomarker [3]
Inborn error of metabolism DISO5FAY Strong Biomarker [3]
Isolated ectopia lentis DISJWTN6 Strong Biomarker [4]
Melnick-Needles syndrome DIS0KTGM Strong Biomarker [3]
Multiple epiphyseal dysplasia DIS5FZLR Strong Biomarker [3]
Osteochondrodysplasia DIS9SPWW Strong Biomarker [3]
Schwartz-Jampel syndrome DIS3HCR8 Strong Biomarker [3]
Schwartz-Jampel syndrome type 1 DIS42TKQ Strong Biomarker [3]
Spondyloepiphyseal dysplasia DIS1JG9A Strong Biomarker [3]
Spondyloepiphyseal dysplasia tarda, X-linked DIS9EL3M Strong Biomarker [3]
Geleophysic dysplasia DISZOO1G Disputed Biomarker [5]
Ehlers-Danlos syndrome DISSVBRR Limited Autosomal dominant [2]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 2 (ADAMTSL2). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of ADAMTS-like protein 2 (ADAMTSL2). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of ADAMTS-like protein 2 (ADAMTSL2). [11]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of ADAMTS-like protein 2 (ADAMTSL2). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of ADAMTS-like protein 2 (ADAMTSL2). [8]
Obeticholic acid DM3Q1SM Approved Obeticholic acid decreases the expression of ADAMTS-like protein 2 (ADAMTSL2). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of ADAMTS-like protein 2 (ADAMTSL2). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of ADAMTS-like protein 2 (ADAMTSL2). [13]
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References

1 Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia. J Med Genet. 2016 Jul;53(7):457-64. doi: 10.1136/jmedgenet-2015-103647. Epub 2016 Apr 11.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199.
4 ADAMTS proteins as modulators of microfibril formation and function.Matrix Biol. 2015 Sep;47:34-43. doi: 10.1016/j.matbio.2015.05.004. Epub 2015 May 7.
5 Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia.Matrix Biol. 2019 Sep;82:38-53. doi: 10.1016/j.matbio.2019.02.001. Epub 2019 Feb 7.
6 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.
7 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
8 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.
9 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.
10 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
11 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.
12 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
13 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.