Details of Drug Off-Target (DOT)

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

DOT Name Protein dispatched homolog 1 (DISP1)
Gene Name DISP1
Related Disease
Gastrointestinal stromal tumour ( )
Non-small-cell lung cancer ( )
Polydactyly ( )
Trichohepatoenteric syndrome ( )
Holoprosencephaly ( )
Congenital diaphragmatic hernia ( )
Ebola virus infection ( )
Holoprosencephaly 5 ( )
UniProt ID
DISP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6XE6; 7E2G; 7E2H; 7E2I
Pfam ID
PF02460
Sequence
MAMSNGNNDFVVLSNSSIATSAANPSPLTPCDGDHAAQQLTPKEATRTKVSPNGCLQLNG
TVKSSFLPLDNQRMPQMLPQCCHPCPYHHPLTSHSSHQECHPEAGPAAPSALASCCMQPH
SEYSASLCPNHSPVYQTTCCLQPSPSFCLHHPWPDHFQHQPVQQHIANIRPSRPFKLPKS
YAALIADWPVVVLGMCTMFIVVCALVGVLVPELPDFSDPLLGFEPRGTAIGQRLVTWNNM
VKNTGYKATLANYPFKYADEQAKSHRDDRWSDDHYEREKREVDWNFHKDSFFCDVPSDRY
SRVVFTSSGGETLWNLPAIKSMCNVDNSRIRSHPQFGDLCQRTTAASCCPSWTLGNYIAI
LNNRSSCQKIVERDVSHTLKLLRTCAKHYQNGTLGPDCWDMAARRKDQLKCTNVPRKCTK
YNAVYQILHYLVDKDFMTPKTADYATPALKYSMLFSPTEKGESMMNIYLDNFENWNSSDG
VTTITGIEFGIKHSLFQDYLLMDTVYPAIAIVIVLLVMCVYTKSMFITLMTMFAIISSLI
VSYFLYRVVFHFEFFPFMNLTALIILVGIGADDAFVLCDVWNYTKFDKPHAETSETVSIT
LQHAALSMFVTSFTTAAAFYANYVSNITAIRCFGVYAGTAILVNYVLMVTWLPAVVVLHE
RYLLNIFTCFKKPQQQIYDNKSCWTVACQKCHKVLFAISEASRIFFEKVLPCIVIKFRYL
WLFWFLALTVGGAYIVCINPKMKLPSLELSEFQVFRSSHPFERYDAEYKKLFMFERVHHG
EELHMPITVIWGVSPEDNGNPLNPKSKGKLTLDSSFNIASPASQAWILHFCQKLRNQTFF
YQTDEQDFTSCFIETFKQWMENQDCDEPALYPCCSHWSFPYKQEIFELCIKRAIMELERS
TGYHLDSKTPGPRFDINDTIRAVVLEFQSTYLFTLAYEKMHQFYKEVDSWISSELSSAPE
GLSNGWFVSNLEFYDLQDSLSDGTLIAMGLSVAVAFSVMLLTTWNIIISLYAIISIAGTI
FVTVGSLVLLGWELNVLESVTISVAVGLSVDFAVHYGVAYRLAPDPDREGKVIFSLSRVG
SAMAMAALTTFVAGAMMMPSTVLAYTQLGTFMMLIMCISWAFATFFFQCMCRCLGPQGTC
GQIPLPKKLQCSAFSHALSTSPSDKGQSKTHTINAYHLDPRGPKSELEHEFYELEPLASH
SCTAPEKTTYEETHICSEFFNSQAKNLGMPVHAAYNSELSKSTESDAGSALLQPPLEQHT
VCHFFSLNQRCSCPDAYKHLNYGPHSCQQMGDCLCHQCSPTTSSFVQIQNGVAPLKATHQ
AVEGFVHPITHIHHCPCLQGRVKPAGMQNSLPRNFFLHPVQHIQAQEKIGKTNVHSLQRS
IEEHLPKMAEPSSFVCRSTGSLLKTCCDPENKQRELCKNRDVSNLESSGGTENKAGGKVE
LSLSQTDASVNSEHFNQNEPKVLFNHLMGEAGCRSCPNNSQSCGRIVRVKCNSVDCQMPN
MEANVPAVLTHSELSGESLLIKTL
Function
Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal. Synergizes with SCUBE2 to cause an increase in SHH secretion.
KEGG Pathway
Hedgehog sig.ling pathway (hsa04340 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastrointestinal stromal tumour DIS6TJYS Strong Biomarker [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [2]
Polydactyly DIS25BMZ Strong Genetic Variation [3]
Trichohepatoenteric syndrome DISL3ODF Strong Biomarker [4]
Holoprosencephaly DISR35EC Supportive Autosomal recessive [5]
Congenital diaphragmatic hernia DIS0IPVU Limited Altered Expression [6]
Ebola virus infection DISJAVM1 Limited Biomarker [7]
Holoprosencephaly 5 DIS2AK05 Limited Autosomal dominant [8]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Protein dispatched homolog 1 (DISP1). [9]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Protein dispatched homolog 1 (DISP1). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein dispatched homolog 1 (DISP1). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Protein dispatched homolog 1 (DISP1). [12]
Testosterone DM7HUNW Approved Testosterone increases the expression of Protein dispatched homolog 1 (DISP1). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Protein dispatched homolog 1 (DISP1). [13]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein dispatched homolog 1 (DISP1). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Protein dispatched homolog 1 (DISP1). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein dispatched homolog 1 (DISP1). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein dispatched homolog 1 (DISP1). [18]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Protein dispatched homolog 1 (DISP1). [19]
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⏷ Show the Full List of 11 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein dispatched homolog 1 (DISP1). [16]
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References

1 Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
2 The hedgehog processing pathway is required for NSCLC growth and survival.Oncogene. 2013 May 2;32(18):2335-45. doi: 10.1038/onc.2012.243. Epub 2012 Jun 25.
3 Holoprosencephaly-Polydactyly syndrome: in search of an etiology.Eur J Med Genet. 2008 Mar-Apr;51(2):106-12. doi: 10.1016/j.ejmg.2007.08.004. Epub 2007 Sep 15.
4 New cases and refinement of the critical region in the 1q41q42 microdeletion syndrome.Eur J Med Genet. 2011 Jan-Feb;54(1):42-9. doi: 10.1016/j.ejmg.2010.10.002. Epub 2010 Oct 15.
5 Recent advances in understanding inheritance of holoprosencephaly. Am J Med Genet C Semin Med Genet. 2018 Jun;178(2):258-269. doi: 10.1002/ajmg.c.31619. Epub 2018 May 22.
6 Expression of dispatched RND transporter family member 1 is decreased in the diaphragmatic and pulmonary mesenchyme of nitrofen-induced congenital diaphragmatic hernia.Pediatr Surg Int. 2019 Jan;35(1):35-40. doi: 10.1007/s00383-018-4374-6. Epub 2018 Oct 31.
7 Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during the 2014 Ebola virus epidemic.PLoS Negl Trop Dis. 2017 May 15;11(5):e0005622. doi: 10.1371/journal.pntd.0005622. eCollection 2017 May.
8 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 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.
11 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.
12 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
13 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 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.
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 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.
18 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
19 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.