Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHO6JWN)

DOT Name Nucleobindin-2 (NUCB2)
Synonyms DNA-binding protein NEFA; Epididymis secretory protein Li 109; Gastric cancer antigen Zg4; Prepronesfatin
Gene Name NUCB2
Related Disease
Rheumatoid arthritis ( )
Anorexia nervosa cachexia ( )
Bladder cancer ( )
Breast neoplasm ( )
Cardiovascular disease ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Coronary atherosclerosis ( )
Depression ( )
Fatty liver disease ( )
Gastric cancer ( )
Hyperglycemia ( )
Lung cancer ( )
Lung carcinoma ( )
Mental disorder ( )
Metabolic disorder ( )
Neoplasm ( )
Non-alcoholic fatty liver disease ( )
Obesity ( )
Parkinson disease ( )
Polycystic ovarian syndrome ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Schizophrenia ( )
Stomach cancer ( )
Thyroid gland papillary carcinoma ( )
Type-1/2 diabetes ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Major depressive disorder ( )
Prostate cancer ( )
Renal cell carcinoma ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Breast cancer ( )
Breast carcinoma ( )
Cerebral infarction ( )
Coronary heart disease ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
High blood pressure ( )
Melanoma ( )
Myocardial infarction ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
UniProt ID
NUCB2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF13499
Sequence
MRWRTILLQYCFLLITCLLTALEAVPIDIDKTKVQNIHPVESAKIEPPDTGLYYDEYLKQ
VIDVLETDKHFREKLQKADIEEIKSGRLSKELDLVSHHVRTKLDELKRQEVGRLRMLIKA
KLDSLQDIGMDHQALLKQFDHLNHLNPDKFESTDLDMLIKAATSDLEHYDKTRHEEFKKY
EMMKEHERREYLKTLNEEKRKEEESKFEEMKKKHENHPKVNHPGSKDQLKEVWEETDGLD
PNDFDPKTFFKLHDVNSDGFLDEQELEALFTKELEKVYDPKNEEDDMVEMEEERLRMREH
VMNEVDTNKDRLVTLEEFLKATEKKEFLEPDSWETLDQQQFFTEEELKEYENIIALQENE
LKKKADELQKQKEELQRQHDQLEAQKLEYHQVIQQMEQKKLQQGIPPSGPAGELKFEPHI
Function
Calcium-binding protein which may have a role in calcium homeostasis. Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3; [Nesfatin-1]: Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance.
Tissue Specificity Predominantly expressed in spleen, testis and normal stomach.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Rheumatoid arthritis DISTSB4J Definitive Altered Expression [1]
Anorexia nervosa cachexia DISFO5RQ Strong Biomarker [2]
Bladder cancer DISUHNM0 Strong Biomarker [3]
Breast neoplasm DISNGJLM Strong Altered Expression [4]
Cardiovascular disease DIS2IQDX Strong Altered Expression [5]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [6]
Colon cancer DISVC52G Strong Altered Expression [3]
Colon carcinoma DISJYKUO Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [7]
Coronary atherosclerosis DISKNDYU Strong Altered Expression [8]
Depression DIS3XJ69 Strong Biomarker [9]
Fatty liver disease DIS485QZ Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
Hyperglycemia DIS0BZB5 Strong Biomarker [12]
Lung cancer DISCM4YA Strong Altered Expression [13]
Lung carcinoma DISTR26C Strong Altered Expression [13]
Mental disorder DIS3J5R8 Strong Biomarker [14]
Metabolic disorder DIS71G5H Strong Altered Expression [15]
Neoplasm DISZKGEW Strong Biomarker [16]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [17]
Obesity DIS47Y1K Strong Biomarker [18]
Parkinson disease DISQVHKL Strong Biomarker [19]
Polycystic ovarian syndrome DISZ2BNG Strong Altered Expression [20]
Prostate carcinoma DISMJPLE Strong Altered Expression [11]
Prostate neoplasm DISHDKGQ Strong Biomarker [21]
Schizophrenia DISSRV2N Strong Biomarker [22]
Stomach cancer DISKIJSX Strong Biomarker [11]
Thyroid gland papillary carcinoma DIS48YMM Strong Biomarker [16]
Type-1/2 diabetes DISIUHAP Strong Biomarker [23]
Urinary bladder cancer DISDV4T7 Strong Biomarker [3]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [3]
Major depressive disorder DIS4CL3X moderate Biomarker [24]
Prostate cancer DISF190Y moderate Altered Expression [11]
Renal cell carcinoma DISQZ2X8 moderate Biomarker [6]
Adult glioblastoma DISVP4LU Disputed Biomarker [25]
Glioblastoma multiforme DISK8246 Disputed Biomarker [25]
Breast cancer DIS7DPX1 Limited Altered Expression [4]
Breast carcinoma DIS2UE88 Limited Altered Expression [4]
Cerebral infarction DISR1WNP Limited Biomarker [26]
Coronary heart disease DIS5OIP1 Limited Altered Expression [8]
Endometrial cancer DISW0LMR Limited Biomarker [27]
Endometrial carcinoma DISXR5CY Limited Biomarker [27]
High blood pressure DISY2OHH Limited Biomarker [18]
Melanoma DIS1RRCY Limited Biomarker [28]
Myocardial infarction DIS655KI Limited Biomarker [26]
Neuroblastoma DISVZBI4 Limited Biomarker [29]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [30]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
22 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 Nucleobindin-2 (NUCB2). [31]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Nucleobindin-2 (NUCB2). [32]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Nucleobindin-2 (NUCB2). [33]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Nucleobindin-2 (NUCB2). [34]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Nucleobindin-2 (NUCB2). [35]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Nucleobindin-2 (NUCB2). [36]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Nucleobindin-2 (NUCB2). [37]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Nucleobindin-2 (NUCB2). [38]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Nucleobindin-2 (NUCB2). [39]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Nucleobindin-2 (NUCB2). [40]
Marinol DM70IK5 Approved Marinol increases the expression of Nucleobindin-2 (NUCB2). [41]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Nucleobindin-2 (NUCB2). [42]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Nucleobindin-2 (NUCB2). [44]
Fenretinide DMRD5SP Phase 3 Fenretinide increases the expression of Nucleobindin-2 (NUCB2). [45]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Nucleobindin-2 (NUCB2). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Nucleobindin-2 (NUCB2). [47]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Nucleobindin-2 (NUCB2). [48]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Nucleobindin-2 (NUCB2). [49]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Nucleobindin-2 (NUCB2). [50]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Nucleobindin-2 (NUCB2). [44]
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the expression of Nucleobindin-2 (NUCB2). [38]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Nucleobindin-2 (NUCB2). [51]
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⏷ Show the Full List of 22 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Pioglitazone DMKJ485 Approved Pioglitazone increases the stability of Nucleobindin-2 (NUCB2). [43]
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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 Nucleobindin-2 (NUCB2). [46]
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References

1 Nesfatin-1 and visfatin expression is associated with reduced atherosclerotic disease risk in patients with rheumatoid arthritis.Peptides. 2018 Apr;102:31-37. doi: 10.1016/j.peptides.2018.02.002. Epub 2018 Feb 21.
2 Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.Brain Res. 2017 Dec 15;1677:33-46. doi: 10.1016/j.brainres.2017.09.024. Epub 2017 Sep 23.
3 Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer.Dis Markers. 2018 Sep 19;2018:4272064. doi: 10.1155/2018/4272064. eCollection 2018.
4 Identification of Nucleobindin-2 as a Potential Biomarker for Breast Cancer Metastasis Using iTRAQ-based Quantitative Proteomic Analysis.J Cancer. 2017 Sep 2;8(15):3062-3069. doi: 10.7150/jca.19619. eCollection 2017.
5 Metabolic and Cardiovascular Actions of Nesfatin-1: Implications in Health and Disease.Curr Pharm Des. 2017;23(10):1453-1464. doi: 10.2174/1381612823666170130154407.
6 A novel function of NUCB2 in promoting the development and invasion of renal cell carcinoma.Oncol Lett. 2018 Feb;15(2):2425-2430. doi: 10.3892/ol.2017.7563. Epub 2017 Dec 8.
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10 Fasting Whole-Body Energy Homeostasis and Hepatic Energy Metabolism in Nondiabetic Humans with Fatty Liver.Oxid Med Cell Longev. 2019 Apr 11;2019:9796175. doi: 10.1155/2019/9796175. eCollection 2019.
11 High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer.Tumour Biol. 2017 Jul;39(7):1010428317703817. doi: 10.1177/1010428317703817.
12 Carbohydrate oxidation and glucose utilisation under hyperglycaemia in aged and young males during exercise at the same relative exercise intensity.Eur J Appl Physiol. 2019 Jan;119(1):235-245. doi: 10.1007/s00421-018-4019-4. Epub 2018 Oct 23.
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15 Increased NEFA levels reduce blood Mg(2+) in hypertriacylglycerolaemic states via direct binding of NEFA to Mg(2).Diabetologia. 2019 Feb;62(2):311-321. doi: 10.1007/s00125-018-4771-3. Epub 2018 Nov 13.
16 High expression of NUCB2 promotes papillary thyroid cancer cells proliferation and invasion.Onco Targets Ther. 2019 Feb 18;12:1309-1318. doi: 10.2147/OTT.S184560. eCollection 2019.
17 Anti-lipoapoptotic effects of Alisma orientalis extract on non-esterified fatty acid-induced HepG2 cells.BMC Complement Altern Med. 2016 Jul 25;16:239. doi: 10.1186/s12906-016-1181-2.
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19 The association of low levels of nesfatin-1 and glucagon-like peptide-1 with oxidative stress in Parkinson's disease.Neurol Sci. 2019 Dec;40(12):2529-2535. doi: 10.1007/s10072-019-03975-4. Epub 2019 Jul 6.
20 The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat.Reprod Fertil Dev. 2020 Feb;32(3):313-321. doi: 10.1071/RD19072.
21 Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
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23 Effects of Nesfatin-1 on Food Intake and Hyperglycemia.J Am Coll Nutr. 2020 May-Jun;39(4):345-351. doi: 10.1080/07315724.2019.1646678. Epub 2019 Aug 1.
24 Evaluating the Levels of Nesfatin-1 and Ghrelin Hormones in Patients with Moderate and Severe Major Depressive Disorders.Psychiatry Investig. 2018 Feb;15(2):214-218. doi: 10.30773/pi.2017.05.24. Epub 2017 Dec 1.
25 Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma.Cancer Biother Radiopharm. 2019 Nov;34(9):581-588. doi: 10.1089/cbr.2019.2829.
26 Protective effects of Nesfatin-1 peptide on cerebral ischemia reperfusion injury via inhibition of neuronal cell death and enhancement of antioxidant defenses.Metab Brain Dis. 2019 Feb;34(1):79-85. doi: 10.1007/s11011-018-0323-2. Epub 2018 Sep 30.
27 Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.Endocr J. 2016;63(3):287-99. doi: 10.1507/endocrj.EJ15-0490. Epub 2016 Feb 4.
28 Regulation of the adaptation to ER stress by KLF4 facilitates melanoma cell metastasis via upregulating NUCB2 expression.J Exp Clin Cancer Res. 2018 Jul 28;37(1):176. doi: 10.1186/s13046-018-0842-z.
29 CRHR1 Mediates the Up-Regulation of Synapsin I Induced by Nesfatin-1 Through ERK 1/2 Signaling in SH-SY5Y Cells.Cell Mol Neurobiol. 2018 Apr;38(3):627-633. doi: 10.1007/s10571-017-0509-x. Epub 2017 Jun 12.
30 Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice.J Endocrinol Invest. 2020 Apr;43(4):515-528. doi: 10.1007/s40618-019-01136-0. Epub 2019 Nov 5.
31 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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