Details of Drug Off-Target (DOT)

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

• DOT Name: CUE domain-containing protein 2 (CUEDC2)
• Gene Name: CUEDC2
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Autism
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colitis
  Colorectal carcinoma
  Glioma
  Lung adenocarcinoma
  Neoplasm
  Ovarian serous adenocarcinoma
  Amyotrophic lateral sclerosis
  Colon cancer
  Colon carcinoma
• UniProt ID: CUED2_HUMAN
• Pfam ID: PF02845
• Sequence:
  MELERIVSAALLAFVQTHLPEADLSGLDEVIFSYVLGVLEDLGPSGPSEENFDMEAFTEM
  MEAYVPGFAHIPRGTIGDMMQKLSGQLSDARNKENLQPQSSGVQGQVPISPEPLQRPEML
  KEETRSSAAAAADTQDEATGAEEELLPGVDVLLEVFPTCSVEQAQWVLAKARGDLEEAVQ
  MLVEGKEEGPAAWEGPNQDLPRRLRGPQKDELKSFILQKYMMVDSAEDQKIHRPMAPKEA
  PKKLIRYIDNQVVSTKGERFKDVRNPEAEEMKATYINLKPARKYRFH
• Function: Down-regulates ESR1 protein levels through the ubiquitination-proteasome pathway, regardless of the presence of 17 beta-estradiol. Also involved in 17 beta-estradiol-induced ESR1 degradation. Controls PGR protein levels through a similar mechanism.
• Tissue Specificity: Significantly up-regulated in breast tumor tissues compared with matched adjacent normal tissues (at protein level). Levels inversely correlate with ESR1 in breast cancers and are lower in low-grade tumors compared to high-grade tumors.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Colitis	DISAF7DD	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[7]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Biomarker	[9]
Amyotrophic lateral sclerosis	DISF7HVM	Disputed	Biomarker	[10]
Colon cancer	DISVC52G	Limited	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of CUE domain-containing protein 2 (CUEDC2).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CUE domain-containing protein 2 (CUEDC2).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CUE domain-containing protein 2 (CUEDC2).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CUE domain-containing protein 2 (CUEDC2).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of CUE domain-containing protein 2 (CUEDC2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of CUE domain-containing protein 2 (CUEDC2).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of CUE domain-containing protein 2 (CUEDC2).	[15]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of CUE domain-containing protein 2 (CUEDC2).	[17]

References

• [1] CUEDC2, a novel interacting partner of the SOCS1 protein, plays important roles in the leukaemogenesis of acute myeloid leukaemia.Cell Death Dis. 2018 Jul 10;9(7):774. doi: 10.1038/s41419-018-0812-6.
• [2] CUE domain-containing protein 2 promotes the Warburg effect and tumorigenesis.EMBO Rep. 2017 May;18(5):809-825. doi: 10.15252/embr.201643617. Epub 2017 Mar 21.
• [3] Replication of previous GWAS hits suggests the association between rs4307059 near MSNP1AS and autism in a Chinese Han population.Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:194-198. doi: 10.1016/j.pnpbp.2018.12.016. Epub 2019 Jan 3.
• [4] CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome.EMBO J. 2007 Apr 4;26(7):1831-42. doi: 10.1038/sj.emboj.7601602. Epub 2007 Mar 8.
• [5] Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer.Cell Rep. 2014 Jun 26;7(6):1982-93. doi: 10.1016/j.celrep.2014.05.007. Epub 2014 May 29.
• [6] Expression of CUEDC2 in colorectal cancer with different invasion and migration abilities.J Int Med Res. 2019 Feb;47(2):905-914. doi: 10.1177/0300060518813072. Epub 2019 Jan 17.
• [7] CUEDC2 suppresses glioma tumorigenicity by inhibiting the activation of STAT3 and NF-B signaling pathway.Int J Oncol. 2017 Jul;51(1):115-127. doi: 10.3892/ijo.2017.4009. Epub 2017 May 17.
• [8] CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma.Oncotarget. 2015 Aug 21;6(24):20685-96. doi: 10.18632/oncotarget.3930.
• [9] CUEDC2 Contributes to Cisplatin-Based Chemotherapy Resistance in Ovarian Serious Carcinoma by Regulating p38 MAPK Signaling.J Cancer. 2019 Apr 21;10(8):1800-1807. doi: 10.7150/jca.29889. eCollection 2019.
• [10] Identification of biomarkers for amyotrophic lateral sclerosis by comprehensive analysis of exosomal mRNAs in human cerebrospinal fluid.BMC Med Genomics. 2019 Jan 10;12(1):7. doi: 10.1186/s12920-019-0473-z.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.