Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO10D1N)

• DOT Name: CXXC-type zinc finger protein 1 (CXXC1)
• Synonyms: CpG-binding protein; PHD finger and CXXC domain-containing protein 1
• Gene Name: CXXC1
• Related Disease:
  Gastric cancer
  Stomach cancer
  Colorectal carcinoma
  Lung cancer
  Neoplasm
  Osteoporosis
  Rett syndrome
  Small lymphocytic lymphoma
  Advanced cancer
  Autoimmune disease
  Nervous system disease
  Nervous system inflammation
• UniProt ID: CXXC1_HUMAN
• PDB ID: 3QMB; 3QMC; 3QMD; 3QMG; 3QMH; 3QMI
• Pfam ID: PF12269 ; PF00628 ; PF02008
• Sequence:
  MEGDGSDPEPPDAGEDSKSENGENAPIYCICRKPDINCFMIGCDNCNEWFHGDCIRITEK
  MAKAIREWYCRECREKDPKLEIRYRHKKSRERDGNERDSSEPRDEGGGRKRPVPDPDLQR
  RAGSGTGVGAMLARGSASPHKSSPQPLVATPSQHHQQQQQQIKRSARMCGECEACRRTED
  CGHCDFCRDMKKFGGPNKIRQKCRLRQCQLRARESYKYFPSSLSPVTPSESLPRPRRPLP
  TQQQPQPSQKLGRIREDEGAVASSTVKEPPEATATPEPLSDEDLPLDPDLYQDFCAGAFD
  DHGLPWMSDTEESPFLDPALRKRAVKVKHVKRREKKSEKKKEERYKRHRQKQKHKDKWKH
  PERADAKDPASLPQCLGPGCVRPAQPSSKYCSDDCGMKLAANRIYEILPQRIQQWQQSPC
  IAEEHGKKLLERIRREQQSARTRLQEMERRFHELEAIILRAKQQAVREDEESNEGDSDDT
  DLQIFCVSCGHPINPRVALRHMERCYAKYESQTSFGSMYPTRIEGATRLFCDVYNPQSKT
  YCKRLQVLCPEHSRDPKVPADEVCGCPLVRDVFELTGDFCRLPKRQCNRHYCWEKLRRAE
  VDLERVRVWYKLDELFEQERNVRTAMTNRAGLLALMLHQTIQHDPLTTDLRSSADR
• Function: Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  XBP1(S) activates chaperone genes (R-HSA-381038)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[5]
Rett syndrome	DISGG5UV	Strong	Genetic Variation	[6]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Autoimmune disease	DISORMTM	Limited	Altered Expression	[9]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[10]
Nervous system inflammation	DISB3X5A	Limited	Genetic Variation	[9]

7 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 CXXC-type zinc finger protein 1 (CXXC1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of CXXC-type zinc finger protein 1 (CXXC1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CXXC-type zinc finger protein 1 (CXXC1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of CXXC-type zinc finger protein 1 (CXXC1).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of CXXC-type zinc finger protein 1 (CXXC1).	[20]

References

• [1] The survival analysis and oncogenic effects of CFP1 and 14-3-3 expression on gastric cancer.Cancer Cell Int. 2019 Aug 31;19:225. doi: 10.1186/s12935-019-0946-3. eCollection 2019.
• [2] Promoter CpG island hypermethylation- and H3K9me3 and H3K27me3-mediated epigenetic silencing targets the deleted in colon cancer (DCC) gene in colorectal carcinogenesis without affecting neighboring genes on chromosomal region 18q21. Carcinogenesis. 2009 Jun;30(6):1041-8. doi: 10.1093/carcin/bgp073. Epub 2009 Mar 27.
• [3] MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers.Oncogene. 2003 May 29;22(22):3506-10. doi: 10.1038/sj.onc.1206574.
• [4] Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus.Clin Cancer Res. 2017 Oct 1;23(19):5846-5857. doi: 10.1158/1078-0432.CCR-17-0285. Epub 2017 May 23.
• [5] Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians.PLoS One. 2015 Dec 31;10(12):e0146072. doi: 10.1371/journal.pone.0146072. eCollection 2015.
• [6] First description of an unusual novel double mutation in MECP2 co-occurring with the m.827A>G mutation in the MT-RNR1 gene associated with angelman-like syndrome.Int J Dev Neurosci. 2019 Dec;79:37-44. doi: 10.1016/j.ijdevneu.2019.10.002. Epub 2019 Oct 21.
• [7] Expression analysis of the epigenetic methyltransferases and methyl-CpG binding protein families in the normal B-cell and B-cell chronic lymphocytic leukemia (CLL).Cancer Biol Ther. 2004 Oct;3(10):989-94. doi: 10.4161/cbt.3.10.1137. Epub 2004 Oct 2.
• [8] MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy.Cancer Discov. 2016 Jan;6(1):45-58. doi: 10.1158/2159-8290.CD-15-0341. Epub 2015 Nov 6.
• [9] Epigenetic initiation of the T(H)17 differentiation program is promoted by Cxxc finger protein 1.Sci Adv. 2019 Oct 9;5(10):eaax1608. doi: 10.1126/sciadv.aax1608. eCollection 2019 Oct.
• [10] The methyl-CpG-binding protein MeCP2 and neurological disease.Biochem Soc Trans. 2008 Aug;36(Pt 4):575-83. doi: 10.1042/BST0360575.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.