Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDVAX6B)

• DOT Name: BCAS3 microtubule associated cell migration factor (BCAS3)
• Synonyms: Breast carcinoma-amplified sequence 3; GAOB1
• Gene Name: BCAS3
• Related Disease:
  Acute myelogenous leukaemia
  Chronic renal failure
  Advanced cancer
  Alzheimer disease
  Brain neoplasm
  Cardiovascular disease
  Chronic obstructive pulmonary disease
  Esophageal adenocarcinoma
  Hengel-Maroofian-Schols syndrome
  Type-1/2 diabetes
  Coronary heart disease
  Chronic kidney disease
  Crohn disease
  Gout
  Urolithiasis
• UniProt ID: BCAS3_HUMAN
• Pfam ID: PF12490 ; PF21034
• Sequence:
  MNEAMATDSPRRPSRCTGGVVVRPQAVTEQSYMESVVTFLQDVVPQAYSGTPLTEEKEKI
  VWVRFENADLNDTSRNLEFHEIHSTGNEPPLLIMIGYSDGMQVWSIPISGEAQELFSVRH
  GPIRAARILPAPQFGAQKCDNFAEKRPLLGVCKSIGSSGTSPPYCCVDLYSLRTGEMVKS
  IQFKTPIYDLHCNKRILVVVLQEKIAAFDSCTFTKKFFVTSCYPCPGPNMNPIALGSRWL
  AYAENKLIRCHQSRGGACGDNIQSYTATVISAAKTLKSGLTMVGKVVTQLTGTLPSGVTE
  DDVAIHSNSRRSPLVPGIITVIDTETVGEGQVLVSEDSDSDGIVAHFPAHEKPVCCMAFN
  TSGMLLVTTDTLGHDFHVFQILTHPWSSSQCAVHHLYTLHRGETEAKVQDICFSHDCRWV
  VVSTLRGTSHVFPINPYGGQPCVRTHMSPRVVNRMSRFQKSAGLEEIEQELTSKQGGRCS
  PVPGLSSSPSGSPLHGKLNSQDSYNNFTNNNPGNPRLSPLPSLMVVMPLAQIKQPMTLGT
  ITKRTGPYLFGAGCFSIKAPCKVKPPPQISPSKSMGGEFCVAAIFGTSRSWFANNAGLKR
  EKDQSKQVVVESLYIISCYGTLVEHMMEPRPLSTAPKISDDTPLEMMTSPRASWTLVRTP
  QWNELQPPFNANHPLLLAADAVQYYQFLLAGLVPPGSPGPITRHGSYDSLASDHSGQEDE
  EWLSQVEIVTHTGPHRRLWMGPQFQFKTIHPSGQTTVISSSSSVLQSHGPSDTPQPLLDF
  DTDDLDLNSLRIQPVRSDPVSMPGSSRPVSDRRGVSTVIDAASGTFDRSVTLLEVCGSWP
  EGFGLRHMSSMEHTEEGLRERLADAMAESPSRDVVGSGTELQREGSIETLSNSSGSTSGS
  IPRNFDGYRSPLPTNESQPLSLFPTGFP
• Function: Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation. Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy. Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures.
• Tissue Specificity: Expressed in stomach, liver, lung, kidney, prostate, testis, thyroid gland, adrenal gland, brain, heart, skeletal muscle, colon, spleen, small intestine, placenta, blood leukocyte and mammary epithelial cells. Expressed in undifferentiated ES cells. Expressed in blood islands and nascent blood vessels derived from differentiated ES cells into embryoid bodies (BD). Expressed in endothelial cells. Not detected in brain. Expressed in brain tumors (at protein level). Expressed in brain. Highly expressed in breast cancers and in glioma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[7]
Esophageal adenocarcinoma	DISODWFP	Strong	Altered Expression	[8]
Hengel-Maroofian-Schols syndrome	DISKMZXP	Strong	Autosomal recessive	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[10]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[11]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[12]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[13]
Gout	DISHC0U7	Limited	Genetic Variation	[14]
Urolithiasis	DISNFTKT	Limited	Genetic Variation	[15]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[27]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of BCAS3 microtubule associated cell migration factor (BCAS3).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of BCAS3 microtubule associated cell migration factor (BCAS3).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of BCAS3 microtubule associated cell migration factor (BCAS3).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BCAS3 microtubule associated cell migration factor (BCAS3).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of BCAS3 microtubule associated cell migration factor (BCAS3).	[25]

References

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• [2] A catalog of genetic loci associated with kidney function from analyses of a million individuals.Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.
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• [9] A de novo 3.54 Mb deletion of 17q22-q23.1 associated with hydrocephalus: a case report and review of literature. Am J Med Genet A. 2011 Dec;155A(12):3082-6. doi: 10.1002/ajmg.a.34307. Epub 2011 Nov 3.
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• [15] Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population.J Am Soc Nephrol. 2019 May;30(5):855-864. doi: 10.1681/ASN.2018090942. Epub 2019 Apr 11.
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• [17] 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.
• [18] 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.
• [19] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
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• [21] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [22] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [23] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
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• [25] 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.
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