Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8P6QNJ)

• DOT Name: Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3)
• Synonyms: Cadherin family member 11; Epidermal growth factor-like protein 1; EGF-like protein 1; Flamingo homolog 1; hFmi1; Multiple epidermal growth factor-like domains protein 2; Multiple EGF-like domains protein 2
• Gene Name: CELSR3
• Related Disease:
  Neoplasm
  Advanced cancer
  Autoimmune disease
  Colorectal carcinoma
  Common variable immunodeficiency
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Paroxysmal nocturnal haemoglobinuria
  Prostate cancer
  Prostate carcinoma
  Tourette syndrome
  Amyotrophic lateral sclerosis
  Crohn disease
  Hirschsprung disease
  Squamous cell carcinoma
  Ulcerative colitis
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: CELR3_HUMAN
• Pfam ID: PF00002 ; PF00028 ; PF00008 ; PF16489 ; PF01825 ; PF02793 ; PF00053 ; PF02210
• Sequence:
  MMARRPPWRGLGGRSTPILLLLLLSLFPLSQEELGGGGHQGWDPGLAATTGPRAHIGGGA
  LALCPESSGVREDGGPGLGVREPIFVGLRGRRQSARNSRGPPEQPNEELGIEHGVQPLGS
  RERETGQGPGSVLYWRPEVSSCGRTGPLQRGSLSPGALSSGVPGSGNSSPLPSDFLIRHH
  GPKPVSSQRNAGTGSRKRVGTARCCGELWATGSKGQGERATTSGAERTAPRRNCLPGASG
  SGPELDSAPRTARTAPASGSAPRESRTAPEPAPKRMRSRGLFRCRFLPQRPGPRPPGLPA
  RPEARKVTSANRARFRRAANRHPQFPQYNYQTLVPENEAAGTAVLRVVAQDPDAGEAGRL
  VYSLAALMNSRSLELFSIDPQSGLIRTAAALDRESMERHYLRVTAQDHGSPRLSATTMVA
  VTVADRNDHSPVFEQAQYRETLRENVEEGYPILQLRATDGDAPPNANLRYRFVGPPAARA
  AAAAAFEIDPRSGLISTSGRVDREHMESYELVVEASDQGQEPGPRSATVRVHITVLDEND
  NAPQFSEKRYVAQVREDVRPHTVVLRVTATDRDKDANGLVHYNIISGNSRGHFAIDSLTG
  EIQVVAPLDFEAEREYALRIRAQDAGRPPLSNNTGLASIQVVDINDHIPIFVSTPFQVSV
  LENAPLGHSVIHIQAVDADHGENARLEYSLTGVAPDTPFVINSATGWVSVSGPLDRESVE
  HYFFGVEARDHGSPPLSASASVTVTVLDVNDNRPEFTMKEYHLRLNEDAAVGTSVVSVTA
  VDRDANSAISYQITGGNTRNRFAISTQGGVGLVTLALPLDYKQERYFKLVLTASDRALHD
  HCYVHINITDANTHRPVFQSAHYSVSVNEDRPMGSTIVVISASDDDVGENARITYLLEDN
  LPQFRIDADSGAITLQAPLDYEDQVTYTLAITARDNGIPQKADTTYVEVMVNDVNDNAPQ
  FVASHYTGLVSEDAPPFTSVLQISATDRDAHANGRVQYTFQNGEDGDGDFTIEPTSGIVR
  TVRRLDREAVSVYELTAYAVDRGVPPLRTPVSIQVMVQDVNDNAPVFPAEEFEVRVKENS
  IVGSVVAQITAVDPDEGPNAHIMYQIVEGNIPELFQMDIFSGELTALIDLDYEARQEYVI
  VVQATSAPLVSRATVHVRLVDQNDNSPVLNNFQILFNNYVSNRSDTFPSGIIGRIPAYDP
  DVSDHLFYSFERGNELQLLVVNQTSGELRLSRKLDNNRPLVASMLVTVTDGLHSVTAQCV
  LRVVIITEELLANSLTVRLENMWQERFLSPLLGRFLEGVAAVLATPAEDVFIFNIQNDTD
  VGGTVLNVSFSALAPRGAGAGAAGPWFSSEELQEQLYVRRAALAARSLLDVLPFDDNVCL
  REPCENYMKCVSVLRFDSSAPFLASASTLFRPIQPIAGLRCRCPPGFTGDFCETELDLCY
  SNPCRNGGACARREGGYTCVCRPRFTGEDCELDTEAGRCVPGVCRNGGTCTDAPNGGFRC
  QCPAGGAFEGPRCEVAARSFPPSSFVMFRGLRQRFHLTLSLSFATVQQSGLLFYNGRLNE
  KHDFLALELVAGQVRLTYSTGESNTVVSPTVPGGLSDGQWHTVHLRYYNKPRTDALGGAQ
  GPSKDKVAVLSVDDCDVAVALQFGAEIGNYSCAAAGVQTSSKKSLDLTGPLLLGGVPNLP
  ENFPVSHKDFIGCMRDLHIDGRRVDMAAFVANNGTMAGCQAKLHFCDSGPCKNSGFCSER
  WGSFSCDCPVGFGGKDCQLTMAHPHHFRGNGTLSWNFGSDMAVSVPWYLGLAFRTRATQG
  VLMQVQAGPHSTLLCQLDRGLLSVTVTRGSGRASHLLLDQVTVSDGRWHDLRLELQEEPG
  GRRGHHVLMVSLDFSLFQDTMAVGSELQGLKVKQLHVGGLPPGSAEEAPQGLVGCIQGVW
  LGSTPSGSPALLPPSHRVNAEPGCVVTNACASGPCPPHADCRDLWQTFSCTCQPGYYGPG
  CVDACLLNPCQNQGSCRHLPGAPHGYTCDCVGGYFGHHCEHRMDQQCPRGWWGSPTCGPC
  NCDVHKGFDPNCNKTNGQCHCKEFHYRPRGSDSCLPCDCYPVGSTSRSCAPHSGQCPCRP
  GALGRQCNSCDSPFAEVTASGCRVLYDACPKSLRSGVWWPQTKFGVLATVPCPRGALGAA
  VRLCDEAQGWLEPDLFNCTSPAFRELSLLLDGLELNKTALDTMEAKKLAQRLREVTGHTD
  HYFSQDVRVTARLLAHLLAFESHQQGFGLTATQDAHFNENLLWAGSALLAPETGDLWAAL
  GQRAPGGSPGSAGLVRHLEEYAATLARNMELTYLNPMGLVTPNIMLSIDRMEHPSSPRGA
  RRYPRYHSNLFRGQDAWDPHTHVLLPSQSPRPSPSEVLPTSSSIENSTTSSVVPPPAPPE
  PEPGISIIILLVYRTLGGLLPAQFQAERRGARLPQNPVMNSPVVSVAVFHGRNFLRGILE
  SPISLEFRLLQTANRSKAICVQWDPPGLAEQHGVWTARDCELVHRNGSHARCRCSRTGTF
  GVLMDASPRERLEGDLELLAVFTHVVVAVSVAALVLTAAILLSLRSLKSNVRGIHANVAA
  ALGVAELLFLLGIHRTHNQLVCTAVAILLHYFFLSTFAWLFVQGLHLYRMQVEPRNVDRG
  AMRFYHALGWGVPAVLLGLAVGLDPEGYGNPDFCWISVHEPLIWSFAGPVVLVIVMNGTM
  FLLAARTSCSTGQREAKKTSALTLRSSFLLLLLVSASWLFGLLAVNHSILAFHYLHAGLC
  GLQGLAVLLLFCVLNADARAAWMPACLGRKAAPEEARPAPGLGPGAYNNTALFEESGLIR
  ITLGASTVSSVSSARSGRTQDQDSQRGRSYLRDNVLVRHGSAADHTDHSLQAHAGPTDLD
  VAMFHRDAGADSDSDSDLSLEEERSLSIPSSESEDNGRTRGRFQRPLCRAAQSERLLTHP
  KDVDGNDLLSYWPALGECEAAPCALQTWGSERRLGLDTSKDAANNNQPDPALTSGDETSL
  GRAQRQRKGILKNRLQYPLVPQTRGAPELSWCRAATLGHRAVPAASYGRIYAGGGTGSLS
  QPASRYSSREQLDLLLRRQLSRERLEEAPAPVLRPLSRPGSQECMDAAPGRLEPKDRGST
  LPRRQPPRDYPGAMAGRFGSRDALDLGAPREWLSTLPPPRRTRDLDPQPPPLPLSPQRQL
  SRDPLLPSRPLDSLSRSSNSREQLDQVPSRHPSREALGPLPQLLRAREDSVSGPSHGPST
  EQLDILSSILASFNSSALSSVQSSSTPLGPHTTATPSATASVLGPSTPRSATSHSISELS
  PDSEVPRSEGHS
• Function: Receptor that may have an important role in cell/cell signaling during nervous system formation.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Common variable immunodeficiency	DISHE7JQ	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[5]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Genetic Variation	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Tourette syndrome	DISX9D54	Strong	Genetic Variation	[8]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[9]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[10]
Hirschsprung disease	DISUUSM1	moderate	Altered Expression	[11]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[12]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[10]
Epithelial ovarian cancer	DIS56MH2	Disputed	Genetic Variation	[13]
Ovarian cancer	DISZJHAP	Disputed	Genetic Variation	[13]
Ovarian neoplasm	DISEAFTY	Disputed	Genetic Variation	[13]

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 Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[22]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[25]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[26]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3).	[23]

References

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• [2] CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis.PeerJ. 2019 Oct 7;7:e7816. doi: 10.7717/peerj.7816. eCollection 2019.
• [3] Evolving spectrum of LRBA deficiency-associated chronic arthritis: is there a causative role in juvenile idiopathic arthritis?.Clin Exp Rheumatol. 2017 Mar-Apr;35(2):327-329. Epub 2017 Jan 27.
• [4] AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4.Biochim Biophys Acta. 2016 Jun;1862(6):1172-81. doi: 10.1016/j.bbadis.2016.03.012. Epub 2016 Apr 12.
• [5] G2-lymphocyte chromosomal radiosensitivity in patients with LPS responsive beige-like anchor protein (LRBA) deficiency.Int J Radiat Biol. 2019 Jun;95(6):680-690. doi: 10.1080/09553002.2019.1577570. Epub 2019 Feb 13.
• [6] Paroxysmal nocturnal hemoglobinuria.Blood. 2014 Oct 30;124(18):2804-11. doi: 10.1182/blood-2014-02-522128. Epub 2014 Sep 18.
• [7] Tissue transglutaminase interacts with protein kinase A anchor protein 13 in prostate cancer.Urol Oncol. 2005 Nov-Dec;23(6):407-12. doi: 10.1016/j.urolonc.2005.04.002.
• [8] De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.Cell Rep. 2018 Sep 25;24(13):3441-3454.e12. doi: 10.1016/j.celrep.2018.08.082.
• [9] Dystrophin-related protein in skeletal muscles in neuromuscular disorders: immunohistochemical study.Acta Neuropathol. 1993;85(3):256-9. doi: 10.1007/BF00227719.
• [10] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [11] Deregulation of the planar cell polarity genes CELSR3 and FZD3 in Hirschsprung disease.Exp Mol Pathol. 2016 Oct;101(2):241-248. doi: 10.1016/j.yexmp.2016.09.003. Epub 2016 Sep 13.
• [12] Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma.Asian Pac J Cancer Prev. 2016;17(1):219-23. doi: 10.7314/apjcp.2016.17.1.219.
• [13] FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway.Cell Death Dis. 2014 Jul 17;5(7):e1346. doi: 10.1038/cddis.2014.302.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] 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.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] 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.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [21] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [22] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [23] 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.
• [24] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [25] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [26] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.