Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6M8M3J)

DOT Name Obscurin-like protein 1 (OBSL1)
Gene Name OBSL1
Related Disease
3M syndrome 2 ( )
Myopathy ( )
Silver-Russell syndrome ( )
Limb-girdle muscular dystrophy ( )
3-M syndrome ( )
UniProt ID
OBSL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2CPC; 2E6P; 2E6Q; 2LU7; 2LVC; 2WP3; 2WWK; 2WWM; 3KNB; 5FM5
Pfam ID
PF07679 ; PF13927
Sequence
MKASSGDQGSPPCFLRFPRPVRVVSGAEAELKCVVLGEPPPVVVWEKGGQQLAASERLSF
PADGAEHGLLLTAALPTDAGVYVCRARNAAGEAYAAAAVTVLEPPASDPELQPAERPLPS
PGSGEGAPVFLTGPRSQWVLRGAEVVLTCRAGGLPEPTLYWEKDGMALDEVWDSSHFALQ
PGRAEDGPGASLALRILAARLPDSGVYVCHARNAHGHAQAGALLQVHQPPESPPADPDEA
PAPVVEPLKCAPKTFWVNEGKHAKFRCYVMGKPEPEIEWHWEGRPLLPDRRRLMYRDRDG
GFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHVKEPRLRFTRPLQDVEGREHGIAVL
ECKVPNSRIPTAWFREDQRLLPCRKYEQIEEGTVRRLIIHRLKADDDGIYLCEMRGRVRT
VANVTVKGPILKRLPRKLDVLEGENAVLLVETLEAGVEGRWSRDGEELPVICQSSSGHMH
ALVLPGVTREDAGEVTFSLGNSRTTTLLRVKCVKHSPPGPPILAEMFKGHKNTVLLTWKP
PEPAPETPFIYRLERQEVGSEDWIQCFSIEKAGAVEVPGDCVPSEGDYRFRICTVSGHGR
SPHVVFHGSAHLVPTARLVAGLEDVQVYDGEDAVFSLDLSTIIQGTWFLNGEELKSNEPE
GQVEPGALRYRIEQKGLQHRLILHAVKHQDSGALVGFSCPGVQDSAALTIQESPVHILSP
QDRVSLTFTTSERVVLTCELSRVDFPATWYKDGQKVEESELLVVKMDGRKHRLILPEAKV
QDSGEFECRTEGVSAFFGVTVQDPPVHIVDPREHVFVHAITSECVMLACEVDREDAPVRW
YKDGQEVEESDFVVLENEGPHRRLVLPATQPSDGGEFQCVAGDECAYFTVTITDVSSWIV
YPSGKVYVAAVRLERVVLTCELCRPWAEVRWTKDGEEVVESPALLLQKEDTVRRLVLPAV
QLEDSGEYLCEIDDESASFTVTVTEPPVRIIYPRDEVTLIAVTLECVVLMCELSREDAPV
RWYKDGLEVEESEALVLERDGPRCRLVLPAAQPEDGGEFVCDAGDDSAFFTVTVTAPPER
IVHPAARSLDLHFGAPGRVELRCEVAPAGSQVRWYKDGLEVEASDALQLGAEGPTRTLTL
PHAQPEDAGEYVCETRHEAITFNVILAEPPVQFLALETTPSPLCVAPGEPVVLSCELSRA
GAPVVWSHNGRPVQEGEGLELHAEGPRRVLCIQAAGPAHAGLYTCQSGAAPGAPSLSFTV
QVAEPPVRVVAPEAAQTRVRSTPGGDLELVVHLSGPGGPVRWYKDGERLASQGRVQLEQA
GARQVLRVQGARSGDAGEYLCDAPQDSRIFLVSVEEPLLVKLVSELTPLTVHEGDDATFR
CEVSPPDADVTWLRNGAVVTPGPQVEMAQNGSSRILTLRGCQLGDAGTVTLRAGSTATSA
RLHVRETELLFLRRLQDVRAEEGQDVCLEVETGRVGAAGAVRWVRGGQPLPHDSRLSMAQ
DGHIHRLFIHGVILADQGTYGCESHHDRTLARLSVRPRQLRVLRPLEDVTISEGGSATFQ
LELSQEGVTGEWARGGVQLYPGPKCHIHSDGHRHRLVLNGLGLADSGCVSFTADSLRCAA
RLIVREVPVTIVRGPHDLEVTEGDTATFECELSQALADVTWEKDGNALTPSPRLRLQALG
TRRLLQLRRCGPSDAGTYSCAVGTARAGPVRLTVRERTVAVLSELRSVSAREGDGATFEC
TVSEVETTGRWELGGRPLRPGARVRIRQEGKKHILVLSELRAEDAGEVRFQAGPAQSLAL
LEVEALPLQMCRHPPREKTVLVGRRAVLEVTVSRSGGHVCWLREGAELCPGDKYEMRSHG
PTHSLVIHDVRPEDQGTYCCQAGQDSTHTRLLVEGN
Function
Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons.
Tissue Specificity Widely expressed, with predominant levels found in the heart.
Reactome Pathway
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
3M syndrome 2 DISFZZ07 Definitive Autosomal recessive [1]
Myopathy DISOWG27 Strong Biomarker [2]
Silver-Russell syndrome DISSVJ1D Strong Genetic Variation [3]
Limb-girdle muscular dystrophy DISI9Y1Z moderate Genetic Variation [4]
3-M syndrome DISGKJY3 Supportive Autosomal recessive [5]
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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 Obscurin-like protein 1 (OBSL1). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Obscurin-like protein 1 (OBSL1). [16]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Obscurin-like protein 1 (OBSL1). [18]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Obscurin-like protein 1 (OBSL1). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Obscurin-like protein 1 (OBSL1). [8]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Obscurin-like protein 1 (OBSL1). [9]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Obscurin-like protein 1 (OBSL1). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Obscurin-like protein 1 (OBSL1). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Obscurin-like protein 1 (OBSL1). [12]
Selenium DM25CGV Approved Selenium increases the expression of Obscurin-like protein 1 (OBSL1). [13]
Rifampicin DM5DSFZ Approved Rifampicin decreases the expression of Obscurin-like protein 1 (OBSL1). [14]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Obscurin-like protein 1 (OBSL1). [15]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Obscurin-like protein 1 (OBSL1). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Obscurin-like protein 1 (OBSL1). [17]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Obscurin-like protein 1 (OBSL1). [19]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Obscurin-like protein 1 (OBSL1). [20]
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⏷ Show the Full List of 13 Drug(s)

References

1 The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1. Am J Hum Genet. 2009 Jun;84(6):801-6. doi: 10.1016/j.ajhg.2009.04.021. Epub 2009 May 28.
2 Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2908-13. doi: 10.1073/pnas.0913736107. Epub 2010 Feb 1.
3 Genetic characterisation of a cohort of children clinically labelled as GH or IGF1 insensitive: diagnostic value of serum IGF1 and height at presentation.Eur J Endocrinol. 2015 Feb;172(2):151-61. doi: 10.1530/EJE-14-0541. Epub 2014 Nov 19.
4 Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band: implications for hereditary myopathies.J Cell Sci. 2008 Jun 1;121(11):1841-51. doi: 10.1242/jcs.028019. Epub 2008 May 13.
5 Three M Syndrome. 2002 Mar 25 [updated 2019 Feb 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
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 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 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.
9 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
10 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
11 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
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 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
14 Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 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.
17 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
18 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.
19 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
20 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.