Details of Drug Off-Target (DOT)

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

DOT Name Secreted frizzled-related protein 5 (SFRP5)
Synonyms sFRP-5; Frizzled-related protein 1b; FRP-1b; Secreted apoptosis-related protein 3; SARP-3
Gene Name SFRP5
Related Disease
Arteriosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiovascular disease ( )
Chronic kidney disease ( )
Chronic obstructive pulmonary disease ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Coronary heart disease ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
leukaemia ( )
Leukemia ( )
Liver cirrhosis ( )
Myelodysplastic syndrome ( )
Non-alcoholic fatty liver disease ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic tumour ( )
Periodontitis ( )
Plasma cell myeloma ( )
Pneumonia ( )
Pneumonitis ( )
Polycystic ovarian syndrome ( )
Small lymphocytic lymphoma ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Urinary bladder neoplasm ( )
Non-insulin dependent diabetes ( )
Atherosclerosis ( )
Melanoma ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Advanced cancer ( )
Fatty liver disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
UniProt ID
SFRP5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF01392 ; PF01759
Sequence
MRAAAAGGGVRTAALALLLGALHWAPARCEEYDYYGWQAEPLHGRSYSKPPQCLDIPADL
PLCHTVGYKRMRLPNLLEHESLAEVKQQASSWLPLLAKRCHSDTQVFLCSLFAPVCLDRP
IYPCRSLCEAVRAGCAPLMEAYGFPWPEMLHCHKFPLDNDLCIAVQFGHLPATAPPVTKI
CAQCEMEHSADGLMEQMCSSDFVVKMRIKEIKIENGDRKLIGAQKKKKLLKPGPLKRKDT
KRLVLHMKNGAGCPCPQLDSLAGSFLVMGRKVDGQLLLMAVYRWDKKNKEMKFAVKFMFS
YPCSLYYPFFYGAAEPH
Function
Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP5 may be involved in determining the polarity of photoreceptor, and perhaps, other cells in the retina.
Tissue Specificity Highly expressed in the retinal pigment epithelium (RPE) and pancreas. Weak expression in heart, liver and muscle.
KEGG Pathway
Wnt sig.ling pathway (hsa04310 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arteriosclerosis DISK5QGC Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Breast neoplasm DISNGJLM Strong Posttranslational Modification [2]
Cardiovascular disease DIS2IQDX Strong Biomarker [3]
Chronic kidney disease DISW82R7 Strong Altered Expression [4]
Chronic obstructive pulmonary disease DISQCIRF Strong Biomarker [5]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [7]
Colorectal neoplasm DISR1UCN Strong Posttranslational Modification [8]
Coronary heart disease DIS5OIP1 Strong Altered Expression [9]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
High blood pressure DISY2OHH Strong Altered Expression [14]
leukaemia DISS7D1V Strong Biomarker [15]
Leukemia DISNAKFL Strong Biomarker [15]
Liver cirrhosis DIS4G1GX Strong Genetic Variation [16]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [17]
Non-alcoholic fatty liver disease DISDG1NL Strong Altered Expression [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Obesity DIS47Y1K Strong Biomarker [20]
Ovarian cancer DISZJHAP Strong Biomarker [21]
Ovarian neoplasm DISEAFTY Strong Biomarker [21]
Pancreatic tumour DIS3U0LK Strong Posttranslational Modification [22]
Periodontitis DISI9JOI Strong Biomarker [23]
Plasma cell myeloma DIS0DFZ0 Strong Posttranslational Modification [24]
Pneumonia DIS8EF3M Strong Biomarker [5]
Pneumonitis DIS88E0K Strong Biomarker [5]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [25]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [26]
Squamous cell carcinoma DISQVIFL Strong Posttranslational Modification [27]
Stomach cancer DISKIJSX Strong Biomarker [11]
Type-1/2 diabetes DISIUHAP Strong Biomarker [14]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [28]
Non-insulin dependent diabetes DISK1O5Z moderate Biomarker [14]
Atherosclerosis DISMN9J3 Disputed Biomarker [29]
Melanoma DIS1RRCY Disputed Altered Expression [30]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [31]
Adenocarcinoma DIS3IHTY Limited Posttranslational Modification [32]
Advanced cancer DISAT1Z9 Limited Posttranslational Modification [33]
Fatty liver disease DIS485QZ Limited Biomarker [34]
Prostate cancer DISF190Y Limited Altered Expression [35]
Prostate carcinoma DISMJPLE Limited Altered Expression [35]
Renal cell carcinoma DISQZ2X8 Limited Posttranslational Modification [36]
Rheumatoid arthritis DISTSB4J Limited Biomarker [37]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Secreted frizzled-related protein 5 (SFRP5). [38]
Triclosan DMZUR4N Approved Triclosan increases the expression of Secreted frizzled-related protein 5 (SFRP5). [40]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Secreted frizzled-related protein 5 (SFRP5). [41]
Folic acid DMEMBJC Approved Folic acid increases the expression of Secreted frizzled-related protein 5 (SFRP5). [42]
Tofacitinib DMBS370 Approved Tofacitinib increases the expression of Secreted frizzled-related protein 5 (SFRP5). [43]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Secreted frizzled-related protein 5 (SFRP5). [44]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Secreted frizzled-related protein 5 (SFRP5). [46]
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⏷ Show the Full List of 7 Drug(s)
2 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 Secreted frizzled-related protein 5 (SFRP5). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Secreted frizzled-related protein 5 (SFRP5). [45]
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References

1 Effect of SFRP5 (Secreted Frizzled-Related Protein 5) on the WNT5A (Wingless-Type Family Member 5A)-Induced Endothelial Dysfunction and Its Relevance With Arterial Stiffness in Human Subjects.Arterioscler Thromb Vasc Biol. 2018 Jun;38(6):1358-1367. doi: 10.1161/ATVBAHA.117.310649. Epub 2018 Apr 19.
2 Epigenetic inactivation of the secreted frizzled-related protein-5 (SFRP5) gene in human breast cancer is associated with unfavorable prognosis.Carcinogenesis. 2008 May;29(5):991-8. doi: 10.1093/carcin/bgn076. Epub 2008 Mar 19.
3 Association of asymptomatic target organ damage with secreted frizzled related protein 5 in the elderly: the Northern Shanghai Study.Clin Interv Aging. 2018 Mar 6;13:389-395. doi: 10.2147/CIA.S155514. eCollection 2018.
4 Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction.Cytokine. 2018 Oct;110:367-373. doi: 10.1016/j.cyto.2018.04.009. Epub 2018 May 25.
5 Downregulation of Sfrp5 in insulin resistant rats promotes macrophage-mediated pulmonary inflammation through activation of Wnt5a/JNK1 signaling.Biochem Biophys Res Commun. 2018 Oct 28;505(2):498-504. doi: 10.1016/j.bbrc.2018.09.070. Epub 2018 Sep 26.
6 Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA.Clin Cancer Res. 2006 Dec 1;12(23):6989-97. doi: 10.1158/1078-0432.CCR-06-1194.
7 SFRP4 was overexpressed in colorectal carcinoma.J Cancer Res Clin Oncol. 2010 Mar;136(3):395-401. doi: 10.1007/s00432-009-0669-2.
8 Silencing of secreted frizzled-related protein genes in MSI colorectal carcinogenesis.Hepatogastroenterology. 2008 Jul-Aug;55(85):1265-8.
9 High Serum Secreted Frizzled-Related Protein 5 Levels Associates with Early Improvement of Cardiac Function Following ST-Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.J Atheroscler Thromb. 2019 Oct 1;26(10):868-878. doi: 10.5551/jat.47019. Epub 2019 Feb 15.
10 CDH1, DLEC1 and SFRP5 methylation panel as a prognostic marker for advanced epithelial ovarian cancer.Epigenomics. 2018 Nov;10(11):1397-1413. doi: 10.2217/epi-2018-0035. Epub 2018 Oct 16.
11 Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer.Oncogene. 2007 Jul 12;26(32):4699-713. doi: 10.1038/sj.onc.1210259. Epub 2007 Feb 5.
12 Epigenetic silencing of SFRP1 and SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway.Int J Cancer. 2014 Aug 1;135(3):635-46. doi: 10.1002/ijc.28697. Epub 2014 Jan 13.
13 Integrative analysis of aberrant Wnt signaling in hepatitis B virus-related hepatocellular carcinoma.World J Gastroenterol. 2015 May 28;21(20):6317-28. doi: 10.3748/wjg.v21.i20.6317.
14 Type 2 diabetes with hypertensive patients results in changes to features of adipocytokines: Leptin, Irisin, LGR4, and Sfrp5.Clin Exp Hypertens. 2019;41(7):645-650. doi: 10.1080/10641963.2018.1529779. Epub 2018 Oct 11.
15 Methylation of SFRP5 is related to multidrug resistance in leukemia cells.Cancer Gene Ther. 2014 Feb;21(2):83-9. doi: 10.1038/cgt.2013.87. Epub 2014 Jan 17.
16 Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma.J Gastroenterol. 2008;43(5):378-89. doi: 10.1007/s00535-008-2170-0. Epub 2008 Jul 1.
17 Methylation of Wnt antagonist genes: a useful prognostic marker for myelodysplastic syndrome.Ann Hematol. 2013 Jan;92(2):199-209. doi: 10.1007/s00277-012-1595-y. Epub 2012 Oct 24.
18 SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women.Ann Hepatol. 2015 Sep-Oct;14(5):666-74.
19 DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer.J Exp Clin Cancer Res. 2012 Sep 25;31(1):80. doi: 10.1186/1756-9966-31-80.
20 Umbilical Cord SFRP5 Levels of Term Newborns in Relation to Normal and Excessive Gestational Weight Gain.Int J Mol Sci. 2019 Jan 30;20(3):595. doi: 10.3390/ijms20030595.
21 Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway.Int J Cancer. 2010 Aug 1;127(3):555-67. doi: 10.1002/ijc.25083.
22 Hypermethylation and aberrant expression of secreted frizzled-related protein genes in pancreatic cancer.World J Gastroenterol. 2008 Jun 7;14(21):3421-4. doi: 10.3748/wjg.14.3421.
23 Secreted frizzled-related protein 5 serum levels in human periodontitis-A nested case-control study.J Clin Periodontol. 2019 May;46(5):522-528. doi: 10.1111/jcpe.13087. Epub 2019 Apr 22.
24 Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma.Cancer Lett. 2009 Aug 18;281(1):24-31. doi: 10.1016/j.canlet.2009.02.002. Epub 2009 Mar 18.
25 The effect of serum and follicular fluid secreted frizzle-related protein-5 on in vitro fertilization outcomes in patients with polycystic ovary syndrome.Mol Biol Rep. 2018 Dec;45(6):2037-2044. doi: 10.1007/s11033-018-4360-z. Epub 2018 Sep 7.
26 CpG island methylation patterns in chronic lymphocytic leukemia.Leuk Lymphoma. 2009 Mar;50(3):419-26. doi: 10.1080/10428190902756594.
27 Promoter methylation of SFRPs gene family in cervical cancer.Gynecol Oncol. 2009 Feb;112(2):301-6. doi: 10.1016/j.ygyno.2008.10.004. Epub 2008 Nov 26.
28 Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection.Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2109-16. doi: 10.1158/1078-0432.CCR-05-2468.
29 Sfrp5/Wnt Pathway: A Protective Regulatory System in Atherosclerotic Cardiovascular Disease.J Interferon Cytokine Res. 2019 Aug;39(8):472-482. doi: 10.1089/jir.2018.0154. Epub 2019 Jun 13.
30 SFRP5 inhibits the migration and invasion of melanoma cells through Wnt signaling pathway.Onco Targets Ther. 2018 Dec 6;11:8761-8772. doi: 10.2147/OTT.S181146. eCollection 2018.
31 Secreted-frizzled related protein 1 is a transcriptional repression target of the t(8;21) fusion protein in acute myeloid leukemia.Blood. 2011 Dec 15;118(25):6638-48. doi: 10.1182/blood-2011-05-354712. Epub 2011 Oct 26.
32 Methylation analysis of SFRP genes family in cervical adenocarcinoma.J Cancer Res Clin Oncol. 2009 Dec;135(12):1665-74. doi: 10.1007/s00432-009-0613-5. Epub 2009 Jun 10.
33 Association between SFRP promoter hypermethylation and different types of cancer: A systematic review and meta-analysis.Oncol Lett. 2019 Oct;18(4):3481-3492. doi: 10.3892/ol.2019.10709. Epub 2019 Aug 2.
34 Sfrp5 interacts with Slurp1 to regulate the accumulation of triglycerides in hepatocyte steatosis model.Biochem Biophys Res Commun. 2019 Apr 30;512(2):256-262. doi: 10.1016/j.bbrc.2019.03.035. Epub 2019 Mar 15.
35 Secreted frizzled-related protein 5 suppresses aggressive phenotype and reverses docetaxel resistance in prostate cancer.J Investig Med. 2019 Aug;67(6):1009-1017. doi: 10.1136/jim-2018-000849. Epub 2019 Feb 20.
36 Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer.Int J Cancer. 2011 Feb 1;128(3):541-50. doi: 10.1002/ijc.25357.
37 Secreted frizzled-related protein 5 suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through down-regulation of c-Jun N-terminal kinase.Rheumatology (Oxford). 2014 Sep;53(9):1704-11. doi: 10.1093/rheumatology/keu167. Epub 2014 Apr 24.
38 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.
39 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.
40 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
41 Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia. Leukemia. 2009 Sep;23(9):1658-66. doi: 10.1038/leu.2009.86. Epub 2009 Apr 23.
42 Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way. Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700260. Epub 2017 Nov 9.
43 White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat Cell Biol. 2015 Jan;17(1):57-67. doi: 10.1038/ncb3075. Epub 2014 Dec 8.
44 Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005 Sep-Oct;25(5):3293-302.
45 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.
46 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.