Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT10QQBC)

DOT Name Talin-2 (TLN2)
Gene Name TLN2
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Hepatocellular carcinoma ( )
Major depressive disorder ( )
Dilated cardiomyopathy ( )
Camptodactyly of fingers ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Temporal lobe epilepsy ( )
Tourette syndrome ( )
UniProt ID
TLN2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6U4K
Pfam ID
PF16511 ; PF00373 ; PF09379 ; PF01608 ; PF09141 ; PF21692 ; PF08913
Sequence
MVALSLKICVRHCNVVKTMQFEPSTAVYDACRVIRERVPEAQTGQASDYGLFLSDEDPRK
GIWLEAGRTLDYYMLRNGDILEYKKKQRPQKIRMLDGSVKTVMVDDSKTVGELLVTICSR
IGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKLHTDDDLNWLDHSR
TFREQGVDENETLLLRRKFFYSDQNVDSRDPVQLNLLYVQARDDILNGSHPVSFEKACEF
GGFQAQIQFGPHVEHKHKPGFLDLKEFLPKEYIKQRGAEKRIFQEHKNCGEMSEIEAKVK
YVKLARSLRTYGVSFFLVKEKMKGKNKLVPRLLGITKDSVMRVDEKTKEVLQEWPLTTVK
RWAASPKSFTLDFGEYQESYYSVQTTEGEQISQLIAGYIDIILKKKQSKDRFGLEGDEES
TMLEESVSPKKSTILQQQFNRTGKAEHGSVALPAVMRSGSSGPETFNVGSMPSPQQQVMV
GQMHRGHMPPLTSAQQALMGTINTSMHAVQQAQDDLSELDSLPPLGQDMASRVWVQNKVD
ESKHEIHSQVDAITAGTASVVNLTAGDPADTDYTAVGCAITTISSNLTEMSKGVKLLAAL
MDDEVGSGEDLLRAARTLAGAVSDLLKAVQPTSGEPRQTVLTAAGSIGQASGDLLRQIGE
NETDERFQDVLMSLAKAVANAAAMLVLKAKNVAQVAEDTVLQNRVIAAATQCALSTSQLV
ACAKVVSPTISSPVCQEQLIEAGKLVDRSVENCVRACQAATTDSELLKQVSAAASVVSQA
LHDLLQHVRQFASRGEPIGRYDQATDTIMCVTESIFSSMGDAGEMVRQARVLAQATSDLV
NAMRSDAEAEIDMENSKKLLAAAKLLADSTARMVEAAKGAAANPENEDQQQRLREAAEGL
RVATNAAAQNAIKKKIVNRLEVAAKQAAAAATQTIAASQNAAVSNKNPAAQQQLVQSCKA
VADHIPQLVQGVRGSQAQAEDLSAQLALIISSQNFLQPGSKMVSSAKAAVPTVSDQAAAM
QLSQCAKNLATSLAELRTASQKAHEACGPMEIDSALNTVQTLKNELQDAKMAAVESQLKP
LPGETLEKCAQDLGSTSKAVGSSMAQLLTCAAQGNEHYTGVAARETAQALKTLAQAARGV
AASTTDPAAAHAMLDSARDVMEGSAMLIQEAKQALIAPGDAERQQRLAQVAKAVSHSLNN
CVNCLPGQKDVDVALKSIGESSKKLLVDSLPPSTKPFQEAQSELNQAAADLNQSAGEVVH
ATRGQSGELAAASGKFSDDFDEFLDAGIEMAGQAQTKEDQIQVIGNLKNISMASSKLLLA
AKSLSVDPGAPNAKNLLAAAARAVTESINQLITLCTQQAPGQKECDNALRELETVKGMLD
NPNEPVSDLSYFDCIESVMENSKVLGESMAGISQNAKTGDLPAFGECVGIASKALCGLTE
AAAQAAYLVGISDPNSQAGHQGLVDPIQFARANQAIQMACQNLVDPGSSPSQVLSAATIV
AKHTSALCNACRIASSKTANPVAKRHFVQSAKEVANSTANLVKTIKALDGDFSEDNRNKC
RIATAPLIEAVENLTAFASNPEFVSIPAQISSEGSQAQEPILVSAKTMLESSSYLIRTAR
SLAINPKDPPTWSVLAGHSHTVSDSIKSLITSIRDKAPGQRECDYSIDGINRCIRDIEQA
SLAAVSQSLATRDDISVEALQEQLTSVVQEIGHLIDPIATAARGEAAQLGHKVTQLASYF
EPLILAAVGVASKILDHQQQMTVLDQTKTLAESALQMLYAAKEGGGNPKAQHTHDAITEA
AQLMKEAVDDIMVTLNEAASEVGLVGGMVDAIAEAMSKLDEGTPPEPKGTFVDYQTTVVK
YSKAIAVTAQEMMTKSVTNPEELGGLASQMTSDYGHLAFQGQMAAATAEPEEIGFQIRTR
VQDLGHGCIFLVQKAGALQVCPTDSYTKRELIECARAVTEKVSLVLSALQAGNKGTQACI
TAATAVSGIIADLDTTIMFATAGTLNAENSETFADHRENILKTAKALVEDTKLLVSGAAS
TPDKLAQAAQSSAATITQLAEVVKLGAASLGSDDPETQVVLINAIKDVAKALSDLISATK
GAASKPVDDPSMYQLKGAAKVMVTNVTSLLKTVKAVEDEATRGTRALEATIECIKQELTV
FQSKDVPEKTSSPEESIRMTKGITMATAKAVAAGNSCRQEDVIATANLSRKAVSDMLTAC
KQASFHPDVSDEVRTRALRFGTECTLGYLDLLEHVLVILQKPTPEFKQQLAAFSKRVAGA
VTELIQAAEAMKGTEWVDPEDPTVIAETELLGAAASIEAAAKKLEQLKPRAKPKQADETL
DFEEQILEAAKSIAAATSALVKSASAAQRELVAQGKVGSIPANAADDGQWSQGLISAARM
VAAATSSLCEAANASVQGHASEEKLISSAKQVAASTAQLLVACKVKADQDSEAMRRLQAA
GNAVKRASDNLVRAAQKAAFGKADDDDVVVKTKFVGGIAQIIAAQEEMLKKERELEEARK
KLAQIRQQQYKFLPTELREDEG
Function
As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity.
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
Focal adhesion (hsa04510 )
Platelet activation (hsa04611 )
Cytoskeleton in muscle cells (hsa04820 )
Shigellosis (hsa05131 )
Human T-cell leukemia virus 1 infection (hsa05166 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [1]
Major depressive disorder DIS4CL3X Strong Biomarker [3]
Dilated cardiomyopathy DISX608J Disputed Biomarker [4]
Camptodactyly of fingers DISYYXU6 Limited Autosomal dominant [5]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Altered Expression [6]
Liver cancer DISDE4BI Limited Altered Expression [6]
Temporal lobe epilepsy DISNOPXX Limited Biomarker [7]
Tourette syndrome DISX9D54 Limited Unknown [8]
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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
2 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 Talin-2 (TLN2). [9]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Talin-2 (TLN2). [24]
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18 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 Talin-2 (TLN2). [10]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Talin-2 (TLN2). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Talin-2 (TLN2). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Talin-2 (TLN2). [13]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Talin-2 (TLN2). [14]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Talin-2 (TLN2). [15]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Talin-2 (TLN2). [16]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Talin-2 (TLN2). [17]
Marinol DM70IK5 Approved Marinol increases the expression of Talin-2 (TLN2). [18]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Talin-2 (TLN2). [19]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Talin-2 (TLN2). [20]
Clozapine DMFC71L Approved Clozapine decreases the expression of Talin-2 (TLN2). [19]
Benzatropine DMF7EXL Approved Benzatropine decreases the expression of Talin-2 (TLN2). [19]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of Talin-2 (TLN2). [21]
Haloperidol DM96SE0 Approved Haloperidol decreases the expression of Talin-2 (TLN2). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Talin-2 (TLN2). [22]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Talin-2 (TLN2). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Talin-2 (TLN2). [25]
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⏷ Show the Full List of 18 Drug(s)

References

1 Both Talin-1 and Talin-2 correlate with malignancy potential of the human hepatocellular carcinoma MHCC-97 L cell.BMC Cancer. 2016 Jan 28;16:45. doi: 10.1186/s12885-016-2076-9.
2 Male-specific epistasis between WWC1 and TLN2 genes is associated with Alzheimer's disease.Neurobiol Aging. 2018 Dec;72:188.e3-188.e12. doi: 10.1016/j.neurobiolaging.2018.08.001. Epub 2018 Aug 9.
3 Serum agrin and talin are increased in major depression while agrin and creatine phosphokinase are associated with chronic fatigue and fibromyalgia symptoms in depression.Metab Brain Dis. 2020 Jan;35(1):225-235. doi: 10.1007/s11011-019-00506-0. Epub 2019 Nov 16.
4 Loss of mouse cardiomyocyte talin-1 and talin-2 leads to -1 integrin reduction, costameric instability, and dilated cardiomyopathy.Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6250-E6259. doi: 10.1073/pnas.1701416114. Epub 2017 Jul 11.
5 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.
6 Talin-1 correlates with reduced invasion and migration in human hepatocellular carcinoma cells.Asian Pac J Cancer Prev. 2014;15(6):2655-61. doi: 10.7314/apjcp.2014.15.6.2655.
7 Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy.Brain Res. 2009 Feb 19;1255:180-9. doi: 10.1016/j.brainres.2008.12.008. Epub 2008 Dec 11.
8 De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
9 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.
10 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
11 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
12 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
13 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.
14 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
15 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
16 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
17 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
18 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
19 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
20 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
21 Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
22 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
23 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.
24 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.
25 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.