Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2C4P70)

DOT Name E3 ubiquitin-protein ligase NEURL1 (NEURL1)
Synonyms EC 2.3.2.27; Neuralized-like protein 1A; h-neu; h-neuralized 1; RING finger protein 67; RING-type E3 ubiquitin transferase NEURL1
Gene Name NEURL1
Related Disease
Adenocarcinoma ( )
Adult glioblastoma ( )
Astrocytoma ( )
Bladder transitional cell carcinoma ( )
Bone osteosarcoma ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Crohn disease ( )
Ductal breast carcinoma in situ ( )
Endometrium adenocarcinoma ( )
Epithelial neoplasm ( )
Lung cancer ( )
Lung carcinoma ( )
Medulloblastoma ( )
Metastatic malignant neoplasm ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Renal cell carcinoma ( )
Serous cystadenocarcinoma ( )
Stomach cancer ( )
Ulcerative colitis ( )
Uterine serous carcinoma ( )
Familial atrial fibrillation ( )
Head-neck squamous cell carcinoma ( )
Melanoma ( )
Colorectal neoplasm ( )
HER2/NEU overexpressing breast cancer ( )
Transitional cell carcinoma ( )
Atrial fibrillation ( )
Breast neoplasm ( )
Carcinoma ( )
Colorectal adenocarcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Glioblastoma multiforme ( )
Invasive ductal breast carcinoma ( )
Mucolipidosis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Schizophrenia ( )
Sialidosis ( )
Tarsal-carpal coalition syndrome ( )
UniProt ID
NEUL1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
2.3.2.27
Pfam ID
PF07177 ; PF13920
Sequence
MGNNFSSIPSLPRGNPSRAPRGHPQNLKDSIGGPFPVTSHRCHHKQKHCPAVLPSGGLPA
TPLLFHPHTKGSQILMDLSHKAVKRQASFCNAITFSNRPVLIYEQVRLKITKKQCCWSGA
LRLGFTSKDPSRIHPDSLPKYACPDLVSQSGFWAKALPEEFANEGNIIAFWVDKKGRVFH
RINDSAVMLFFSGVRTADPLWALVDVYGLTRGVQLLDSELVLPDCLRPRSFTALRRPSLR
READDARLSVSLCDLNVPGADGDEAAPAAGCPIPQNSLNSQHSRALPAQLDGDLRFHALR
AGAHVRILDEQTVARVEHGRDERALVFTSRPVRVAETIFVKVTRSGGARPGALSFGVTTC
DPGTLRPADLPFSPEALVDRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAAAGM
QLCVDASQPLWMLFGLHGTITQIRILGSTILAERGIPSLPCSPASTPTSPSALGSRLSDP
LLSTCSSGPLGSSAGGTAPNSPVSLPESPVTPGLGQWSDECTICYEHAVDTVIYTCGHMC
LCYACGLRLKKALHACCPICRRPIKDIIKTYRSS
Function
Plays a role in hippocampal-dependent synaptic plasticity, learning and memory. Involved in the formation of spines and functional synaptic contacts by modulating the translational activity of the cytoplasmic polyadenylation element-binding protein CPEB3. Promotes ubiquitination of CPEB3, and hence induces CPEB3-dependent mRNA translation activation of glutamate receptor GRIA1 and GRIA2. Can function as an E3 ubiquitin-protein ligase to activate monoubiquitination of JAG1 (in vitro), thereby regulating the Notch pathway. Acts as a tumor suppressor; inhibits malignant cell transformation of medulloblastoma (MB) cells by inhibiting the Notch signaling pathway.
Tissue Specificity
Expressed in brain, testis, pituitary gland, pancreas and bone marrow. Also poorly expressed in malignant astrocytomas and several neuroectodermal tumor cell lines. Weakly expressed in medulloblastoma (MB) compared with normal cerebellar tissues.
Reactome Pathway
Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 )
Constitutive Signaling by NOTCH1 HD Domain Mutants (R-HSA-2691232 )
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 )
NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096 )
NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507 )
Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Biomarker [1]
Adult glioblastoma DISVP4LU Strong Biomarker [2]
Astrocytoma DISL3V18 Strong Altered Expression [3]
Bladder transitional cell carcinoma DISNL46A Strong Altered Expression [4]
Bone osteosarcoma DIST1004 Strong Altered Expression [5]
Cholangiocarcinoma DIS71F6X Strong Genetic Variation [6]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [7]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [8]
Crohn disease DIS2C5Q8 Strong Biomarker [9]
Ductal breast carcinoma in situ DISLCJY7 Strong Biomarker [10]
Endometrium adenocarcinoma DISY6744 Strong Biomarker [11]
Epithelial neoplasm DIS0T594 Strong Altered Expression [12]
Lung cancer DISCM4YA Strong Genetic Variation [13]
Lung carcinoma DISTR26C Strong Biomarker [14]
Medulloblastoma DISZD2ZL Strong Biomarker [15]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [14]
Osteosarcoma DISLQ7E2 Strong Altered Expression [5]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [7]
Serous cystadenocarcinoma DISVK716 Strong Altered Expression [17]
Stomach cancer DISKIJSX Strong Altered Expression [18]
Ulcerative colitis DIS8K27O Strong Biomarker [9]
Uterine serous carcinoma DISAW5MD Strong Biomarker [19]
Familial atrial fibrillation DISL4AGF moderate Biomarker [20]
Head-neck squamous cell carcinoma DISF7P24 moderate Biomarker [21]
Melanoma DIS1RRCY moderate Biomarker [22]
Colorectal neoplasm DISR1UCN Disputed Biomarker [8]
HER2/NEU overexpressing breast cancer DISYKID5 Disputed Biomarker [23]
Transitional cell carcinoma DISWVVDR Disputed Altered Expression [4]
Atrial fibrillation DIS15W6U Limited Genetic Variation [24]
Breast neoplasm DISNGJLM Limited Altered Expression [25]
Carcinoma DISH9F1N Limited Altered Expression [26]
Colorectal adenocarcinoma DISPQOUB Limited Biomarker [27]
Endometrial cancer DISW0LMR Limited Biomarker [28]
Endometrial carcinoma DISXR5CY Limited Biomarker [28]
Glioblastoma multiforme DISK8246 Limited Altered Expression [3]
Invasive ductal breast carcinoma DIS43J58 Limited Altered Expression [29]
Mucolipidosis DISOZ8DI Limited Genetic Variation [30]
Prostate cancer DISF190Y Limited Biomarker [31]
Prostate carcinoma DISMJPLE Limited Biomarker [31]
Schizophrenia DISSRV2N Limited Genetic Variation [32]
Sialidosis DISF3OAZ Limited Genetic Variation [30]
Tarsal-carpal coalition syndrome DISY90L2 Limited Altered Expression [4]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 E3 ubiquitin-protein ligase NEURL1 (NEURL1). [33]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [34]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [35]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [36]
Mifepristone DMGZQEF Approved Mifepristone increases the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [37]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [38]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase NEURL1 (NEURL1). [39]
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⏷ Show the Full List of 6 Drug(s)

References

1 NEU protein overexpression in benign, borderline, and malignant ovarian neoplasms.Gynecol Oncol. 1992 Mar;44(3):245-53. doi: 10.1016/0090-8258(92)90051-j.
2 Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction.Mol Carcinog. 1990;3(4):198-201. doi: 10.1002/mc.2940030406.
3 Differences between phosphotyrosine accumulation and Neu/ErbB-2 receptor expression in astrocytic proliferative processes. Implications for glial oncogenesis.Cancer. 1996 Sep 15;78(6):1272-83. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1272::AID-CNCR16>3.0.CO;2-Y.
4 HER2/neu gene amplification and protein overexpression in G3 pT2 transitional cell carcinoma of the bladder: a role for anti-HER2 therapy?.Eur J Cancer. 2004 Jan;40(1):56-63. doi: 10.1016/j.ejca.2003.08.027.
5 Absence of HER2/neu gene expression in osteosarcoma and skeletal Ewing's sarcoma.Clin Cancer Res. 2002 Mar;8(3):788-93.
6 HER2/neu-directed therapy for biliary tract cancer.J Hematol Oncol. 2015 May 29;8:58. doi: 10.1186/s13045-015-0155-z.
7 Inverse relationship of epidermal growth factor receptor and HER2/neu gene expression in human renal cell carcinoma.Cancer Res. 1990 Aug 1;50(15):4504-9.
8 Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.PLoS Genet. 2007 Sep;3(9):1709-23. doi: 10.1371/journal.pgen.0030157. Epub 2007 Jul 31.
9 The use of selected neutrophil protein plasma concentrations in the diagnosis of Crohn's disease and ulcerative colitis - a preliminary report.Postepy Hig Med Dosw (Online). 2017 Apr 6;71(0):243-253. doi: 10.5604/01.3001.0010.3810.
10 Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.Am J Surg Pathol. 2019 Sep;43(9):1221-1228. doi: 10.1097/PAS.0000000000001300.
11 Estrogens and glucocorticoids induce the expression of c-erbB2/NEU receptor in Ishikawa human endometrial cells.Life Sci. 1997;61(11):1083-95. doi: 10.1016/s0024-3205(97)00617-6.
12 Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer.Int J Oncol. 2004 Dec;25(6):1769-80.
13 Somatic mutations of the HER2 in metastatic breast cancer.Tumour Biol. 2014 Dec;35(12):11851-4. doi: 10.1007/s13277-014-2414-y. Epub 2014 Oct 19.
14 ERBB2-induced inflammation in lung carcinogenesis.Mol Biol Rep. 2012 Aug;39(8):7911-7. doi: 10.1007/s11033-012-1635-7. Epub 2012 May 1.
15 Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma.Neuro Oncol. 2010 Dec;12(12):1244-56. doi: 10.1093/neuonc/noq091. Epub 2010 Sep 16.
16 Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer.Int J Cancer. 1998 Dec 9;78(6):766-74. doi: 10.1002/(sici)1097-0215(19981209)78:6<766::aid-ijc15>3.0.co;2-l.
17 Marked heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma.Genes Chromosomes Cancer. 2013 Dec;52(12):1178-86. doi: 10.1002/gcc.22113. Epub 2013 Oct 7.
18 Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma.J Cancer Res Clin Oncol. 1992;118(6):474-9. doi: 10.1007/BF01629433.
19 Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro.Tumour Biol. 2015 Jul;36(7):5505-13. doi: 10.1007/s13277-015-3218-4. Epub 2015 Feb 11.
20 Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
21 Personalized Medicine Approach for an Exceptional Response to Multiple-recurrent and Metastatic HER2-positive Oropharyngeal Squamous Cell Carcinoma.Ann Otol Rhinol Laryngol. 2017 Apr;126(4):334-339. doi: 10.1177/0003489416687309. Epub 2017 Jan 6.
22 Targeting NEU Protein in Melanoma Cells with Non-Thermal Atmospheric Pressure Plasma and Gold Nanoparticles.J Biomed Nanotechnol. 2015 May;11(5):900-5. doi: 10.1166/jbn.2015.1999.
23 Polymalic acid-based nanobiopolymer provides efficient systemic breast cancer treatment by inhibiting both HER2/neu receptor synthesis and activity.Cancer Res. 2011 Feb 15;71(4):1454-64. doi: 10.1158/0008-5472.CAN-10-3093. Epub 2011 Feb 8.
24 PITX2 and NEURL1 SNP polymorphisms in Hungarian atrial fibrillation patients determined by quantitative real-time PCR and melting curve analysis.J Biotechnol. 2019 Jun 20;299:44-49. doi: 10.1016/j.jbiotec.2019.04.022. Epub 2019 Apr 27.
25 Designing a HER2/neu promoter to drive alpha1,3galactosyltransferase expression for targeted anti-alphaGal antibody-mediated tumor cell killing.Breast Cancer Res. 2005;7(4):R487-94. doi: 10.1186/bcr1034. Epub 2005 May 3.
26 Physical basis of the 'magnification rule' for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer.Diagn Pathol. 2018 Mar 12;13(1):19. doi: 10.1186/s13000-018-0696-x.
27 Clinicopathological relevance of HER2/neu and a related gene-protein cubic regression correlation in colorectal adenocarcinomas in Taiwan.Int J Oncol. 2005 Apr;26(4):933-43.
28 A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer.Clin Proteomics. 2018 Dec 1;15:38. doi: 10.1186/s12014-018-9216-y. eCollection 2018.
29 Centromere 17 copy number alteration: negative prognostic factor in invasive breast cancer?.Arch Pathol Lab Med. 2012 Sep;136(9):993-1000. doi: 10.5858/arpa.2011-0327-OA.
30 Generation of novel induced pluripotent stem cell (iPSC) line from a 16-year-old sialidosis patient with NEU-1 gene mutation.Stem Cell Res. 2018 Apr;28:39-43. doi: 10.1016/j.scr.2018.01.024. Epub 2018 Jan 31.
31 A transductionally retargeted adenoviral vector for virotherapy of Her2/neu-expressing prostate cancer.Hum Gene Ther. 2012 Jan;23(1):70-82. doi: 10.1089/hum.2011.016. Epub 2011 Oct 12.
32 Genome-wide association study of schizophrenia in Ashkenazi Jews.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):649-59. doi: 10.1002/ajmg.b.32349. Epub 2015 Jul 21.
33 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.
34 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
35 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.
36 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
37 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
38 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
39 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.