Details of Drug Off-Target (DOT)

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

• DOT Name: Cysteine-rich secretory protein 3 (CRISP3)
• Synonyms: CRISP-3; Specific granule protein of 28 kDa; SGP28
• Gene Name: CRISP3
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Carcinoma
  Castration-resistant prostate carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Hepatitis C virus infection
  Metastatic malignant neoplasm
  Neoplasm
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Rheumatoid arthritis
  Sjogren syndrome
  Stomach cancer
  Chronic pancreatitis
  Periodontitis
• UniProt ID: CRIS3_HUMAN
• Pfam ID: PF00188 ; PF08562
• Sequence:
  MTLFPVLLFLVAGLLPSFPANEDKDPAFTALLTTQTQVQREIVNKHNELRRAVSPPARNM
  LKMEWNKEAAANAQKWANQCNYRHSNPKDRMTSLKCGENLYMSSASSSWSQAIQSWFDEY
  NDFDFGVGPKTPNAVVGHYTQVVWYSSYLVGCGNAYCPNQKVLKYYYVCQYCPAGNWANR
  LYVPYEQGAPCASCPDNCDDGLCTNGCKYEDLYSNCKSLKLTLTCKHQLVRDSCKASCNC
  SNSIY
• Tissue Specificity: Salivary gland, pancreas and prostate > epididymis, ovary, thymus and colon.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[8]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[10]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[11]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[6]
Chronic pancreatitis	DISBUOMJ	Limited	Altered Expression	[12]
Periodontitis	DISI9JOI	Limited	Genetic Variation	[13]

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 Cysteine-rich secretory protein 3 (CRISP3).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[16]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[17]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[18]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cysteine-rich secretory protein 3 (CRISP3).	[18]

1 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 Cysteine-rich secretory protein 3 (CRISP3).	[20]

References

• [1] Cysteine-rich secretory protein-3: a potential biomarker for prostate cancer.Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1419-26.
• [2] Immunohistochemical detection of cysteine-rich secretory protein 3 in tissue and in serum from men with cancer or benign enlargement of the prostate gland.Prostate. 2006 May 1;66(6):591-603. doi: 10.1002/pros.20342.
• [3] Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene.PLoS One. 2011;6(7):e22317. doi: 10.1371/journal.pone.0022317. Epub 2011 Jul 21.
• [4] Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.Prostate Cancer Prostatic Dis. 2010 Dec;13(4):369-75. doi: 10.1038/pcan.2010.25. Epub 2010 Aug 3.
• [5] External validation of a 'response score' after neoadjuvant chemotherapy in patients with high-grade serous ovarian carcinoma with complete clinical response.Int J Gynecol Cancer. 2020 Jan;30(1):67-73. doi: 10.1136/ijgc-2019-000561. Epub 2019 Nov 21.
• [6] A retrospective comparative exploratory study on two methylentetrahydrofolate reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients.BMC Cancer. 2014 Feb 3;14:58. doi: 10.1186/1471-2407-14-58.
• [7] Cysteine-rich secretory protein 3 inhibits hepatitis C virus at the initial phase of infection.Biochem Biophys Res Commun. 2014 Jul 25;450(2):1076-82. doi: 10.1016/j.bbrc.2014.06.106. Epub 2014 Jun 27.
• [8] Androgen receptor mediated epigenetic regulation of CRISP3 promoter in prostate cancer cells.J Steroid Biochem Mol Biol. 2018 Jul;181:20-27. doi: 10.1016/j.jsbmb.2018.02.012. Epub 2018 Feb 22.
• [9] Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1.Mol Cell Biochem. 2016 Jan;411(1-2):11-21. doi: 10.1007/s11010-015-2564-2. Epub 2015 Sep 14.
• [10] Caught in a Trap? Proteomic Analysis of Neutrophil Extracellular Traps in Rheumatoid Arthritis and Systemic Lupus Erythematosus.Front Immunol. 2019 Mar 11;10:423. doi: 10.3389/fimmu.2019.00423. eCollection 2019.
• [11] Androgen deficiency and defective intracrine processing of dehydroepiandrosterone in salivary glands in Sjgren's syndrome.J Rheumatol. 2008 Nov;35(11):2229-35. doi: 10.3899/jrheum.080220. Epub 2008 Oct 1.
• [12] Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.Histol Histopathol. 2003 Apr;18(2):425-33. doi: 10.14670/HH-18.425.
• [13] Salivary Cytokine Biomarker Concentrations in Relation to Obesity and Periodontitis.J Clin Med. 2019 Dec 5;8(12):2152. doi: 10.3390/jcm8122152.
• [14] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [15] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [16] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [17] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [18] 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.
• [19] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [20] 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.