Details of Drug Off-Target (DOT)

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

• DOT Name: Cysteine-rich protein 2 (CRIP2)
• Synonyms: CRP-2; Protein ESP1
• Gene Name: CRIP2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Epilepsy
  Esophageal squamous cell carcinoma
  Neoplasm
  Schizophrenia
  Thyroid gland carcinoma
  Colorectal carcinoma
  Cutaneous squamous cell carcinoma
• UniProt ID: CRIP2_HUMAN
• PDB ID: 2CU8
• Pfam ID: PF00412
• Sequence:
  MASKCPKCDKTVYFAEKVSSLGKDWHKFCLKCERCSKTLTPGGHAEHDGKPFCHKPCYAT
  LFGPKGVNIGGAGSYIYEKPLAEGPQVTGPIEVPAARAEERKASGPPKGPSRASSVTTFT
  GEPNTCPRCSKKVYFAEKVTSLGKDWHRPCLRCERCGKTLTPGGHAEHDGQPYCHKPCYG
  ILFGPKGVNTGAVGSYIYDRDPEGKVQP
• Tissue Specificity: Widespread tissue expression; highest levels in the heart.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Epilepsy	DISBB28L	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[5]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[6]

4 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 Cysteine-rich protein 2 (CRIP2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cysteine-rich protein 2 (CRIP2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cysteine-rich protein 2 (CRIP2).	[22]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Cysteine-rich protein 2 (CRIP2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cysteine-rich protein 2 (CRIP2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cysteine-rich protein 2 (CRIP2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Cysteine-rich protein 2 (CRIP2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cysteine-rich protein 2 (CRIP2).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cysteine-rich protein 2 (CRIP2).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cysteine-rich protein 2 (CRIP2).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cysteine-rich protein 2 (CRIP2).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cysteine-rich protein 2 (CRIP2).	[15]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cysteine-rich protein 2 (CRIP2).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cysteine-rich protein 2 (CRIP2).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Cysteine-rich protein 2 (CRIP2).	[18]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Cysteine-rich protein 2 (CRIP2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cysteine-rich protein 2 (CRIP2).	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cysteine-rich protein 2 (CRIP2).	[23]

References

• [1] The impact of cysteine-rich intestinal protein 1 (CRIP1) in human breast cancer.Mol Cancer. 2013 Apr 9;12:28. doi: 10.1186/1476-4598-12-28.
• [2] Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function and Structure.Molecules. 2019 Oct 12;24(20):3672. doi: 10.3390/molecules24203672.
• [3] The LIM domain protein, CRIP2, promotes apoptosis in esophageal squamous cell carcinoma.Cancer Lett. 2012 Mar;316(1):39-45. doi: 10.1016/j.canlet.2011.10.020. Epub 2011 Oct 20.
• [4] The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.Cell Physiol Biochem. 2017;43(5):2037-2046. doi: 10.1159/000484184. Epub 2017 Oct 23.
• [5] Cysteine-rich intestinal protein 1 suppresses apoptosis and chemosensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation.J Exp Clin Cancer Res. 2019 Mar 8;38(1):120. doi: 10.1186/s13046-019-1117-z.
• [6] HOXA9 inhibits HIF-1-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development.Nat Commun. 2018 Apr 16;9(1):1480. doi: 10.1038/s41467-018-03914-5.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] 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.
• [18] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [19] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [20] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [21] 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.
• [22] 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.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [24] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.