Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOMOG3R)

• DOT Name: Cullin-associated NEDD8-dissociated protein 2 (CAND2)
• Synonyms: Cullin-associated and neddylation-dissociated protein 2; Epididymis tissue protein Li 169; TBP-interacting protein of 120 kDa B; TBP-interacting protein 120B; p120 CAND2
• Gene Name: CAND2
• Related Disease:
  Advanced cancer
  Clubfoot
  Non-insulin dependent diabetes
  Atrial fibrillation
  Familial atrial fibrillation
  Obesity
  Simpson-Golabi-Behmel syndrome type 1
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CAND2_HUMAN
• Pfam ID: PF08623
• Sequence:
  MSTAAFHISSLLEKMTSSDKDFRFMATSDLMSELQKDSIQLDEDSERKVVKMLLRLLEDK
  NGEVQNLAVKCLGPLVVKVKEYQVETIVDTLCTNMRSDKEQLRDIAGIGLKTVLSELPPA
  ATGSGLATNVCRKITGQLTSAIAQQEDVAVQLEALDILSDMLSRLGVPLGAFHASLLHCL
  LPQLSSPRLAVRKRAVGALGHLAAACSTDLFVELADHLLDRLPGPRVPTSPTAIRTLIQC
  LGSVGRQAGHRLGAHLDRLVPLVEDFCNLDDDELRESCLQAFEAFLRKCPKEMGPHVPNV
  TSLCLQYIKHDPNYNYDSDEDEEQMETEDSEFSEQESEDEYSDDDDMSWKVRRAAAKCIA
  ALISSRPDLLPDFHCTLAPVLIRRFKEREENVKADVFTAYIVLLRQTQPPKGWLEAMEEP
  TQTGSNLHMLRGQVPLVVKALQRQLKDRSVRARQGCFSLLTELAGVLPGSLAEHMPVLVS
  GIIFSLADRSSSSTIRMDALAFLQGLLGTEPAEAFHPHLPILLPPVMACVADSFYKIAAE
  ALVVLQELVRALWPLHRPRMLDPEPYVGEMSAVTLARLRATDLDQEVKERAISCMGHLVG
  HLGDRLGDDLEPTLLLLLDRLRNEITRLPAIKALTLVAVSPLQLDLQPILAEALHILASF
  LRKNQRALRLATLAALDALAQSQGLSLPPSAVQAVLAELPALVNESDMHVAQLAVDFLAT
  VTQAQPASLVEVSGPVLSELLRLLRSPLLPAGVLAAAEGFLQALVGTRPPCVDYAKLISL
  LTAPVYEQAVDGGPGLHKQVFHSLARCVAALSAACPQEAASTASRLVCDARSPHSSTGVK
  VLAFLSLAEVGQVAGPGHQRELKAVLLEALGSPSEDVRAAASYALGRVGAGSLPDFLPFL
  LEQIEAEPRRQYLLLHSLREALGAAQPDSLKPYAEDIWALLFQRCEGAEEGTRGVVAECI
  GKLVLVNPSFLLPRLRKQLAAGRPHTRSTVITAVKFLISDQPHPIDPLLKSFIGEFMESL
  QDPDLNVRRATLAFFNSAVHNKPSLVRDLLDDILPLLYQETKIRRDLIREVEMGPFKHTV
  DDGLDVRKAAFECMYSLLESCLGQLDICEFLNHVEDGLKDHYDIRMLTFIMVARLATLCP
  APVLQRVDRLIEPLRATCTAKVKAGSVKQEFEKQDELKRSAMRAVAALLTIPEVGKSPIM
  ADFSSQIRSNPELAALFESIQKDSASAPSTDSMELS
• Function: Probable assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes.
• Tissue Specificity: Expressed in epididymis (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Clubfoot	DISLXT4S	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	moderate	Genetic Variation	[3]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[4]
Obesity	DIS47Y1K	moderate	Biomarker	[5]
Simpson-Golabi-Behmel syndrome type 1	DISYV73N	moderate	Altered Expression	[5]
Prostate cancer	DISF190Y	Limited	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[6]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[13]

2 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 Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cullin-associated NEDD8-dissociated protein 2 (CAND2).	[14]

References

• [1] Hepatic transcriptome and proteome analyses provide new insights into the regulator mechanism of dietary avicularin in diabetic mice.Food Res Int. 2019 Nov;125:108570. doi: 10.1016/j.foodres.2019.108570. Epub 2019 Jul 19.
• [2] Evaluation of CAND2 and WNT7a as candidate genes for congenital idiopathic clubfoot.Clin Orthop Relat Res. 2009 May;467(5):1201-5. doi: 10.1007/s11999-008-0701-x. Epub 2009 Jan 22.
• [3] Genomic Variants in NEURL, GJA1 and CUX2 Significantly Increase Genetic Susceptibility to Atrial Fibrillation.Sci Rep. 2018 Feb 19;8(1):3297. doi: 10.1038/s41598-018-21611-7.
• [4] 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.
• [5] Detecting epistasis within chromatin regulatory circuitry reveals CAND2 as a novel susceptibility gene for obesity.Int J Obes (Lond). 2019 Mar;43(3):450-456. doi: 10.1038/s41366-018-0069-2. Epub 2018 May 1.
• [6] Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Dis Markers. 2015;2015:241301. doi: 10.1155/2015/241301. Epub 2015 Sep 28.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] 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.
• [13] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [14] 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.