Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4B2O0)

DOT Name Probetacellulin (BTC)
Gene Name BTC
Related Disease
Erythropoietic protoporphyria ( )
Hyperglycemia ( )
Biliary tract cancer ( )
Brachydactyly type C ( )
Breast adenocarcinoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Hyperinsulinemia ( )
Malignant soft tissue neoplasm ( )
Neoplasm ( )
Nephrotic syndrome ( )
Otitis media ( )
Pancreatic cancer ( )
Sarcoma ( )
Schizophrenia ( )
Type-1/2 diabetes ( )
Autoimmune disease ( )
Gastric cancer ( )
Gastrointestinal stromal tumour ( )
Stomach cancer ( )
Adult glioblastoma ( )
Advanced cancer ( )
Glaucoma/ocular hypertension ( )
Insulinoma ( )
Type-1 diabetes ( )
UniProt ID
BTC_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1IOX; 1IP0
Sequence
MDRAARCSGASSLPLLLALALGLVILHCVVADGNSTRSPETNGLLCGDPEENCAATTTQS
KRKGHFSRCPKQYKHYCIKGRCRFVVAEQTPSCVCDEGYIGARCERVDLFYLRGDRGQIL
VICLIAVMVVFIILVIGVCTCCHPLRKRRKRKKKEEEMETLGKDITPINEDIEETNIA
Function Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.
Tissue Specificity Synthesized in several tissues and tumor cells. Predominantly expressed in pancreas and small intestine.
KEGG Pathway
ErbB sig.ling pathway (hsa04012 )
Reactome Pathway
Signaling by ERBB4 (R-HSA-1236394 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
PI3K events in ERBB4 signaling (R-HSA-1250342 )
SHC1 events in ERBB4 signaling (R-HSA-1250347 )
Nuclear signaling by ERBB4 (R-HSA-1251985 )
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by EGFR (R-HSA-177929 )
GRB2 events in EGFR signaling (R-HSA-179812 )
GAB1 signalosome (R-HSA-180292 )
SHC1 events in EGFR signaling (R-HSA-180336 )
EGFR downregulation (R-HSA-182971 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
EGFR interacts with phospholipase C-gamma (R-HSA-212718 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303 )
RAF/MAP kinase cascade (R-HSA-5673001 )
ERBB2 Regulates Cell Motility (R-HSA-6785631 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
ERBB2 Activates PTK6 Signaling (R-HSA-8847993 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
Downregulation of ERBB2 signaling (R-HSA-8863795 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Signaling by ERBB2 (R-HSA-1227986 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Erythropoietic protoporphyria DISH4BY0 Definitive Biomarker [1]
Hyperglycemia DIS0BZB5 Definitive Biomarker [2]
Biliary tract cancer DISBNYQL Strong Biomarker [3]
Brachydactyly type C DISZ8FTZ Strong Biomarker [4]
Breast adenocarcinoma DISMPHJ0 Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Altered Expression [7]
Carcinoma DISH9F1N Strong Biomarker [8]
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [9]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [10]
Glioblastoma multiforme DISK8246 Strong Biomarker [11]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [12]
Hyperinsulinemia DISIDWT6 Strong Biomarker [13]
Malignant soft tissue neoplasm DISTC6NO Strong Genetic Variation [14]
Neoplasm DISZKGEW Strong Biomarker [15]
Nephrotic syndrome DISSPSC2 Strong Genetic Variation [16]
Otitis media DISGZDUO Strong Biomarker [17]
Pancreatic cancer DISJC981 Strong Genetic Variation [14]
Sarcoma DISZDG3U Strong Genetic Variation [14]
Schizophrenia DISSRV2N Strong Altered Expression [18]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [19]
Autoimmune disease DISORMTM moderate Biomarker [20]
Gastric cancer DISXGOUK moderate Biomarker [21]
Gastrointestinal stromal tumour DIS6TJYS moderate Biomarker [22]
Stomach cancer DISKIJSX moderate Biomarker [21]
Adult glioblastoma DISVP4LU Disputed Biomarker [11]
Advanced cancer DISAT1Z9 Limited Altered Expression [23]
Glaucoma/ocular hypertension DISLBXBY Limited Altered Expression [24]
Insulinoma DISIU1JS Limited Biomarker [25]
Type-1 diabetes DIS7HLUB Limited Biomarker [26]
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⏷ Show the Full List of 31 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Probetacellulin (BTC). [27]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Probetacellulin (BTC). [28]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Probetacellulin (BTC). [29]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Probetacellulin (BTC). [30]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Probetacellulin (BTC). [31]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Probetacellulin (BTC). [32]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Probetacellulin (BTC). [34]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Probetacellulin (BTC). [36]
Dibutyl phthalate DMEDGKO Investigative Dibutyl phthalate decreases the expression of Probetacellulin (BTC). [37]
All-trans-retinal DM6CEVB Investigative All-trans-retinal decreases the expression of Probetacellulin (BTC). [28]
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⏷ Show the Full List of 10 Drug(s)
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 Probetacellulin (BTC). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Probetacellulin (BTC). [35]
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References

1 Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury.Cell Mol Biol (Noisy-le-grand). 2009 Feb 16;55(1):29-37.
2 Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats.Stem Cells Dev. 2011 Feb;20(2):223-32. doi: 10.1089/scd.2009.0490. Epub 2010 Oct 26.
3 Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs.BMC Med Genomics. 2019 May 16;12(1):62. doi: 10.1186/s12920-019-0521-8.
4 Building MOF Nanocomposites with Oxidized Graphitic Carbon Nitride Nanospheres: The Effect of Framework Geometry on the Structural Heterogeneity.Molecules. 2019 Dec 11;24(24):4529. doi: 10.3390/molecules24244529.
5 Hydrogen peroxide and endothelin-1 are novel activators of betacellulin ectodomain shedding.J Cell Biochem. 2006 Oct 1;99(2):609-23. doi: 10.1002/jcb.20968.
6 Genes up- and down-regulated by dermcidin in breast cancer: a microarray analysis.Genet Mol Res. 2008 Sep 30;7(3):925-32. doi: 10.4238/vol7-3x-meeting009.
7 ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis.Ann Oncol. 2008 Jan;19(1):73-80. doi: 10.1093/annonc/mdm431. Epub 2007 Oct 24.
8 Heregulin-dependent autocrine loop regulates growth of K-ras but not erbB-2 transformed rat thyroid epithelial cells.J Cell Physiol. 1998 Aug;176(2):383-91. doi: 10.1002/(SICI)1097-4652(199808)176:2<383::AID-JCP17>3.0.CO;2-4.
9 Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
10 Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer.Cancer Res Treat. 2018 Oct;50(4):1351-1361. doi: 10.4143/crt.2017.487. Epub 2018 Jan 17.
11 Betacellulin drives therapy resistance in glioblastoma.Neuro Oncol. 2020 Apr 15;22(4):457-469. doi: 10.1093/neuonc/noz206.
12 Expression of betacellulin and epidermal growth factor receptor in hepatocellular carcinoma: implications for angiogenesis.Hum Pathol. 2006 Oct;37(10):1324-32. doi: 10.1016/j.humpath.2006.04.022. Epub 2006 Jul 27.
13 The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1.Hum Mol Genet. 2008 Feb 15;17(4):478-89. doi: 10.1093/hmg/ddm325. Epub 2007 Nov 7.
14 Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy.Oncotarget. 2017 Aug 24;8(44):77415-77423. doi: 10.18632/oncotarget.20492. eCollection 2017 Sep 29.
15 Zwitterionic chitooligosaccharide-modified ink-blue titanium dioxide nanoparticles with inherent immune activation for enhanced photothermal therapy.Biomater Sci. 2019 Nov 19;7(12):5027-5034. doi: 10.1039/c9bm01170f.
16 Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome.J Am Soc Nephrol. 2018 Jul;29(7):2000-2013. doi: 10.1681/ASN.2017111185. Epub 2018 Jun 14.
17 Growth factors and their receptors in the middle ear mucosa during otitis media.Laryngoscope. 2002 Mar;112(3):420-3. doi: 10.1097/00005537-200203000-00002.
18 Reduced density of ADAM 12-immunoreactive oligodendrocytes in the anterior cingulate white matter of patients with schizophrenia.World J Biol Psychiatry. 2010 Apr;11(3):556-66. doi: 10.3109/15622970903497936.
19 Remission of diabetes by beta-cell regeneration in diabetic mice treated with a recombinant adenovirus expressing betacellulin.Mol Ther. 2008 May;16(5):854-61. doi: 10.1038/mt.2008.22. Epub 2008 Mar 18.
20 Identification and Optimization of Novel Cathepsin C Inhibitors Derived from EGFR Inhibitors.J Med Chem. 2019 Jun 27;62(12):5901-5919. doi: 10.1021/acs.jmedchem.9b00631. Epub 2019 Jun 17.
21 Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer.Pathobiology. 2017;84(4):210-217. doi: 10.1159/000464250. Epub 2017 Apr 12.
22 Up-regulated expression of ADAM17 in gastrointestinal stromal tumors: coexpression with EGFR and EGFR ligands.Cancer Sci. 2009 Apr;100(4):654-62. doi: 10.1111/j.1349-7006.2009.01089.x. Epub 2009 Mar 1.
23 Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.Cell Signal. 2020 Jan;65:109439. doi: 10.1016/j.cellsig.2019.109439. Epub 2019 Oct 22.
24 Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma.Am J Physiol Cell Physiol. 2018 Dec 1;315(6):C839-C849. doi: 10.1152/ajpcell.00324.2017. Epub 2018 Sep 5.
25 4-Methylcatechol stimulates apoptosis and reduces insulin secretion by decreasing betacellulin and inhibin beta-A in INS-1 beta-cells.Hum Exp Toxicol. 2018 Nov;37(11):1123-1130. doi: 10.1177/0960327118758365. Epub 2018 Feb 23.
26 Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice.Exp Mol Med. 2014 May 30;46(5):e98. doi: 10.1038/emm.2014.24.
27 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
28 Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol. 2006 Apr;126(4):732-9. doi: 10.1038/sj.jid.5700202.
29 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.
30 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
31 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
32 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
33 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.
34 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.
35 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.
36 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
37 Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro. Reprod Toxicol. 2017 Apr;69:13-18.