Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD3ZJST)

• DOT Name: Cerebellar degeneration-related protein 2 (CDR2)
• Synonyms: Major Yo paraneoplastic antigen; Paraneoplastic cerebellar degeneration-associated antigen
• Gene Name: CDR2
• Related Disease:
  Metastatic malignant neoplasm
  Advanced cancer
  Alzheimer disease
  Autoimmune polyendocrine syndrome type 1
  Autoimmune polyendocrinopathy
  B-cell small lymphocytic lymphoma
  Breast neoplasm
  Candidiasis
  Cerebellar degeneration
  Dementia
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Kidney cancer
  Multiple sclerosis
  Neoplasm
  Oral candidiasis
  Ovarian cancer
  Ovarian neoplasm
  Papillary renal cell carcinoma
  Paraneoplastic syndrome
  Renal carcinoma
  Small lymphocytic lymphoma
  Vulvovaginal Candidiasis
  Autoimmune disease
  Follicular lymphoma
  Nervous system inflammation
  Rett syndrome
• UniProt ID: CDR2_HUMAN
• Sequence:
  MLAENLVEEFEMKEDEPWYDHQDLQQDLQLAAELGKTLLDRNTELEDSVQQMYTTNQEQL
  QEIEYLTKQVELLRQMNEQHAKVYEQLDVTARELEETNQKLVADSKASQQKILSLTETIE
  CLQTNIDHLQSQVEELKSSGQGRRSPGKCDQEKPAPSFACLKELYDLRQHFVYDHVFAEK
  ITSLQGQPSPDEEENEHLKKTVTMLQAQLSLERQKRVTMEEEYGLVLKENSELEQQLGAT
  GAYRARALELEAEVAEMRQMLQSEHPFVNGVEKLVPDSLYVPFKEPSQSLLEEMFLTVPE
  SHRKPLKRSSSETILSSLAGSDIVKGHEETCIRRAKAVKQRGISLLHEVDTQYSALKVKY
  EELLKKCQEEQDSLSHKAVQTSRAAAKDLTGVNAQSEPVASGWELASVNPEPVSSPTTPP
  EYKALFKEIFSCIKKTKQEIDEQRTKYRSLSSHS

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metastatic malignant neoplasm	DIS86UK6	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Autoimmune polyendocrine syndrome type 1	DISWJP8J	Strong	Biomarker	[4]
Autoimmune polyendocrinopathy	DISOLDB2	Strong	Altered Expression	[4]
B-cell small lymphocytic lymphoma	DISETZ8S	Strong	Genetic Variation	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Candidiasis	DISIRYMU	Strong	Genetic Variation	[7]
Cerebellar degeneration	DISPBCM3	Strong	Biomarker	[8]
Dementia	DISXL1WY	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[1]
Kidney cancer	DISBIPKM	Strong	Biomarker	[11]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Oral candidiasis	DISAVKAH	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[11]
Paraneoplastic syndrome	DISJUN66	Strong	Biomarker	[11]
Renal carcinoma	DISER9XT	Strong	Biomarker	[11]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[14]
Vulvovaginal Candidiasis	DISRCR6D	moderate	Altered Expression	[15]
Autoimmune disease	DISORMTM	Limited	Biomarker	[16]
Follicular lymphoma	DISVEUR6	Limited	Genetic Variation	[17]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[16]
Rett syndrome	DISGG5UV	Limited	Biomarker	[18]

10 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 Cerebellar degeneration-related protein 2 (CDR2).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[23]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[24]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cerebellar degeneration-related protein 2 (CDR2).	[25]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cerebellar degeneration-related protein 2 (CDR2).	[30]

3 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 decreases the methylation of Cerebellar degeneration-related protein 2 (CDR2).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cerebellar degeneration-related protein 2 (CDR2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cerebellar degeneration-related protein 2 (CDR2).	[31]

References

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• [2] Induction of cytotoxic T lymphocytes specific for paraneoplastic cerebellar degeneration-associated antigen in vivo by DNA immunization.J Autoimmun. 2001 Dec;17(4):297-302. doi: 10.1006/jaut.2001.0553.
• [3] Gullibility may be a warning sign of Alzheimer's disease dementia.Int Psychogeriatr. 2019 Mar;31(3):363-370. doi: 10.1017/S1041610218000844. Epub 2018 Jun 25.
• [4] ADH1 expression inversely correlates with CDR1 and CDR2 in Candida albicans from chronic oral candidosis in APECED (APS-I) patients.FEMS Yeast Res. 2011 Sep;11(6):494-8. doi: 10.1111/j.1567-1364.2011.00739.x. Epub 2011 Jun 16.
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• [7] Quantification of CDR1 Gene Expression in Fluconazole Resistant Candida Glabrata Strains Using Real-time PCR.Iran J Public Health. 2017 Aug;46(8):1118-1122.
• [8] Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.Neuropathol Appl Neurobiol. 2019 Feb;45(2):141-156. doi: 10.1111/nan.12492. Epub 2018 May 24.
• [9] Association of plasma endothelial lipase levels on cognitive impairment.BMC Psychiatry. 2019 Jun 19;19(1):187. doi: 10.1186/s12888-019-2174-8.
• [10] Utility of paraneoplastic antigens as biomarkers for surveillance and prediction of recurrence in ovarian cancer.Cancer Biomark. 2017 Dec 6;20(4):369-387. doi: 10.3233/CBM-170652.
• [11] Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response.Oncogene. 2009 Sep 17;28(37):3274-85. doi: 10.1038/onc.2009.186. Epub 2009 Jul 6.
• [12] Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes.J Immunol. 1998 Jul 15;161(2):1034-44.
• [13] T cells presenting viral antigens or autoantigens induce cytotoxic T cell anergy.JCI Insight. 2017 Nov 2;2(21):e96173. doi: 10.1172/jci.insight.96173.
• [14] IGHV gene insertions and deletions in chronic lymphocytic leukemia: "CLL-biased" deletions in a subset of cases with stereotyped receptors.Eur J Immunol. 2006 Jul;36(7):1963-74. doi: 10.1002/eji.200535751.
• [15] Alcohol dehydrogenase I expression correlates with CDR1, CDR2 and FLU1 expression in Candida albicans from patients with vulvovaginal candidiasis.Chin Med J (Engl). 2013;126(11):2098-102.
• [16] Immunity to TCR peptides in multiple sclerosis. II. T cell recognition of V beta 5.2 and V beta 6.1 CDR2 peptides.J Immunol. 1994 Mar 1;152(5):2520-9.
• [17] Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation.Leukemia. 2002 Apr;16(4):636-44. doi: 10.1038/sj.leu.2402405.
• [18] Mutation screening in Rett syndrome patients.J Med Genet. 2000 Apr;37(4):250-5. doi: 10.1136/jmg.37.4.250.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] 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.
• [21] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [22] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [23] 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.
• [24] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [25] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [26] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [27] 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.
• [28] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [29] 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.
• [30] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [31] 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.