Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGQ8JOZ)

DOT Name	Centrin-1 (CETN1)
Synonyms	Caltractin isoform 2
Gene Name	CETN1
Related Disease	Acute myelogenous leukaemia ( ) Allergic asthma ( ) Alzheimer disease ( ) Amyloidosis ( ) Asthma ( ) Atopic dermatitis ( ) Breast cancer ( ) Cholangiocarcinoma ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Cystic fibrosis ( ) Dermatitis ( ) Gastric cancer ( ) Graves disease ( ) Hepatocellular carcinoma ( ) Matthew-Wood syndrome ( ) Melanoma ( ) Multiple sclerosis ( ) Myositis disease ( ) Non-small-cell lung cancer ( ) Pancreatic cancer ( ) Pancreatitis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Psoriasis ( ) Renal cell carcinoma ( ) Rhabdomyosarcoma ( ) Schizophrenia ( ) Skin disease ( ) Stomach cancer ( ) Testicular cancer ( ) Bone osteosarcoma ( ) Brain disease ( ) Breast carcinoma ( ) Cardiovascular disease ( ) Lung cancer ( ) Lung carcinoma ( ) Osteosarcoma ( ) Peripheral arterial disease ( ) Colorectal carcinoma ( ) Advanced cancer ( ) Colon adenocarcinoma ( ) Metastatic malignant neoplasm ( ) Neoplasm ( ) Tauopathy ( ) Thyroid cancer ( ) Thyroid gland carcinoma ( ) Thyroid tumor ( )
UniProt ID	CETN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF13499
Sequence	MASGFKKPSAASTGQKRKVAPKPELTEDQKQEVREAFDLFDVDGSGTIDAKELKVAMRAL GFEPRKEEMKKMISEVDREGTGKISFNDFLAVMTQKMSEKDTKEEILKAFRLFDDDETGK ISFKNLKRVANELGENLTDEELQEMIDEADRDGDGEVNEEEFLRIMKKTSLY
Function	Plays a fundamental role in microtubule-organizing center structure and function. Plays a role in sperm cilia formation.
Reactome Pathway	Late endosomal microautophagy (R-HSA-9615710 ) Aggrephagy (R-HSA-9646399 ) Chaperone Mediated Autophagy (R-HSA-9613829 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[10]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Graves disease	DISU4KOQ	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[14]
Melanoma	DIS1RRCY	Strong	Biomarker	[15]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[16]
Myositis disease	DISCIXF0	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[17]
Pancreatic cancer	DISJC981	Strong	Biomarker	[14]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[18]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Psoriasis	DIS59VMN	Strong	Altered Expression	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[20]
Schizophrenia	DISSRV2N	Strong	Biomarker	[21]
Skin disease	DISDW8R6	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[11]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[14]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[22]
Brain disease	DIS6ZC3X	moderate	Genetic Variation	[23]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[24]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[23]
Lung cancer	DISCM4YA	moderate	Biomarker	[25]
Lung carcinoma	DISTR26C	moderate	Biomarker	[25]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[22]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[26]
Colorectal carcinoma	DIS5PYL0	Disputed	Biomarker	[27]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[23]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[28]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[29]
Neoplasm	DISZKGEW	Limited	Biomarker	[22]
Tauopathy	DISY2IPA	Limited	Biomarker	[30]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[31]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[31]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[31]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Centrin-1 (CETN1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Centrin-1 (CETN1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Centrin-1 (CETN1).	[34]
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References

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2	Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation.Clin Exp Allergy. 2011 Jun;41(6):878-89. doi: 10.1111/j.1365-2222.2011.03714.x. Epub 2011 Mar 21.
3	Curcuminoid submicron particle ameliorates cognitive deficits and decreases amyloid pathology in Alzheimer's disease mouse model.Oncotarget. 2018 Jan 31;9(12):10681-10697. doi: 10.18632/oncotarget.24369. eCollection 2018 Feb 13.
4	Chaperoning Against Amyloid Aggregation: Monitoring In Vitro and In Vivo.Methods Mol Biol. 2019;1929:135-154. doi: 10.1007/978-1-4939-9030-6_10.
5	Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium.Exp Dermatol. 2007 Aug;16(8):685-91. doi: 10.1111/j.1600-0625.2007.00587.x.
6	EF Hand Protein IBA2 Promotes Cell Proliferation in Breast Cancers via Transcriptional Control of Cyclin D1.Cancer Res. 2016 Aug 1;76(15):4535-45. doi: 10.1158/0008-5472.CAN-15-2927. Epub 2016 Jun 4.
7	Calcium-binding protein S100P is a novel diagnostic marker of cholangiocarcinoma.Cancer Sci. 2011 Jan;102(1):150-6. doi: 10.1111/j.1349-7006.2010.01757.x. Epub 2010 Oct 13.
8	Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma.Cancer Lett. 2002 Jan 10;175(1):71-7. doi: 10.1016/s0304-3835(01)00724-8.
9	S100A4-induced cell motility and metastasis is restricted by the Wnt/-catenin pathway inhibitor calcimycin in colon cancer cells.Mol Biol Cell. 2011 Sep;22(18):3344-54. doi: 10.1091/mbc.E10-09-0739. Epub 2011 Jul 27.
10	Serum concentrations of a granulocyte-derived calcium-binding protein in cystic fibrosis patients and heterozygotes.Clin Chim Acta. 1987 Nov 30;170(1):45-55. doi: 10.1016/0009-8981(87)90382-2.
11	Downregulation of 425G>a variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer.J Cancer Res Clin Oncol. 2015 Apr;141(4):691-703. doi: 10.1007/s00432-014-1830-0. Epub 2014 Sep 30.
12	A 63 kDa skeletal muscle protein associated with eye muscle inflammation in Graves' disease is identified as the calcium binding protein calsequestrin.Autoimmunity. 1999;29(1):1-9. doi: 10.3109/08916939908995967.
13	Overexpression of caltractin gene in tumor-infiltrating lymphocytes.Int J Oncol. 1998 Dec;13(6):1135-40. doi: 10.3892/ijo.13.6.1135.
14	Evaluation of novel highly specific antibodies to cancer testis antigen Centrin-1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer.Cancer Med. 2019 Sep;8(11):5289-5300. doi: 10.1002/cam4.2379. Epub 2019 Jul 16.
15	The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma.J Biol Chem. 2010 Aug 27;285(35):27487-27498. doi: 10.1074/jbc.M110.155382. Epub 2010 Jun 29.
16	Intravitreal S100B Injection Leads to Progressive Glaucoma Like Damage in Retina and Optic Nerve.Front Cell Neurosci. 2018 Sep 26;12:312. doi: 10.3389/fncel.2018.00312. eCollection 2018.
17	Clinical significance of calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer.Thorac Cancer. 2018 Jul;9(7):800-804. doi: 10.1111/1759-7714.12649. Epub 2018 May 7.
18	The calcium binding protein S100A9 is essential for pancreatic leukocyte infiltration and induces disruption of cell-cell contacts.J Cell Physiol. 2008 Aug;216(2):558-67. doi: 10.1002/jcp.21433.
19	DNA methylation and immunohistochemical analysis of the S100A4 calcium binding protein in human prostate cancer.Prostate. 2007 Mar 1;67(4):341-7. doi: 10.1002/pros.20401.
20	Expression of memory, differentiation, and repression of c-myc and p53 genes in human RD/TE-671 cells induced by a ureido-derivative of pyridine (UDP-4).Cell Growth Differ. 1996 Jun;7(6):797-809.
21	Molecular profiles of parvalbumin-immunoreactive neurons in the superior temporal cortex in schizophrenia.J Neurogenet. 2014 Mar-Jun;28(1-2):70-85. doi: 10.3109/01677063.2013.878339. Epub 2014 Mar 17.
22	Clinicopathologic significance of S100A4 expression in osteosarcoma.Eur Rev Med Pharmacol Sci. 2014;18(6):833-9.
23	S100 proteins: Diagnostic and prognostic biomarkers in laboratory medicine.Biochim Biophys Acta Mol Cell Res. 2019 Jul;1866(7):1197-1206. doi: 10.1016/j.bbamcr.2018.10.015. Epub 2018 Oct 28.
24	The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene expression in human breast cancer cells.Biochem Biophys Res Commun. 2012 Oct 19;427(2):336-42. doi: 10.1016/j.bbrc.2012.09.057. Epub 2012 Sep 18.
25	Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells.Mol Med Rep. 2015 Mar;11(3):2118-24. doi: 10.3892/mmr.2014.2936. Epub 2014 Nov 13.
26	Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease.J Am Coll Cardiol. 2018 Jan 2;71(1):53-65. doi: 10.1016/j.jacc.2017.10.072.
27	Calbindin 2 (CALB2) regulates 5-fluorouracil sensitivity in colorectal cancer by modulating the intrinsic apoptotic pathway.PLoS One. 2011;6(5):e20276. doi: 10.1371/journal.pone.0020276. Epub 2011 May 24.
28	The calcium-binding protein calretinin-22k, an alternative splicing product of the calretinin gene is expressed in several colon adeno carcinoma cell lines.Cell Calcium. 1996 Jul;20(1):63-72. doi: 10.1016/s0143-4160(96)90051-2.
29	Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.Breast Cancer Res. 2014 Oct 14;16(5):454. doi: 10.1186/s13058-014-0454-2.
30	A novel calcium-binding protein is associated with tau proteins in tauopathy.J Neurochem. 2008 Jul;106(1):96-106. doi: 10.1111/j.1471-4159.2008.05339.x. Epub 2008 Jul 1.
31	RAGE Mediates the Pro-Migratory Response of Extracellular S100A4 in Human Thyroid Cancer Cells.Thyroid. 2015 May;25(5):514-27. doi: 10.1089/thy.2014.0257. Epub 2015 Apr 3.
32	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.
33	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.
34	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.