Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5SV0E4)

DOT Name Beta-defensin 1 (DEFB1)
Synonyms BD-1; hBD-1; Defensin, beta 1
Gene Name DEFB1
Related Disease
Periodontal disease ( )
Acne vulgaris ( )
Acute lymphocytic leukaemia ( )
Asthma ( )
Atopic dermatitis ( )
Autoimmune disease ( )
Bipolar disorder ( )
Carcinoma ( )
Colitis ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Dental caries ( )
Depression ( )
Gastritis ( )
Gingivitis ( )
Human papillomavirus infection ( )
Lung carcinoma ( )
Major depressive disorder ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
Tuberculosis ( )
Type-1/2 diabetes ( )
Ulcerative colitis ( )
Vitiligo ( )
leukaemia ( )
Leukemia ( )
Neoplasm ( )
Periodontitis ( )
Prostate cancer ( )
Stroke ( )
Type-1 diabetes ( )
Advanced cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Contact dermatitis ( )
Cystic fibrosis ( )
Hyperglycemia ( )
Liver cancer ( )
Obesity ( )
Renal cell carcinoma ( )
UniProt ID
DEFB1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1E4S; 1IJU; 1IJV; 1KJ5; 2NLB; 2NLC; 2NLD; 2NLE; 2NLF; 2NLG; 2NLH; 2NLP; 2NLQ; 2NLS; 2PLZ
Pfam ID
PF00711
Sequence
MRTSYLLLFTLCLLLSEMASGGNFLTGLGHRSDHYNCVSSGGQCLYSACPIFTKIQGTCY
RGKAKCCK
Function
Has bactericidal activity. May act as a ligand for C-C chemokine receptor CCR6. Positively regulates the sperm motility and bactericidal activity in a CCR6-dependent manner. Binds to CCR6 and triggers Ca2+ mobilization in the sperm which is important for its motility.
Tissue Specificity Blood plasma. Sperm. Highly expressed in the lower head and midpiece of sperm. Significantly reduced levels found in the sperms of asthenozoospermia and leukocytospermia patients (at protein level).
KEGG Pathway
ABC transporters (hsa02010 )
Staphylococcus aureus infection (hsa05150 )
Reactome Pathway
Defensins (R-HSA-1461973 )
Beta defensins (R-HSA-1461957 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Periodontal disease DISJQHVN Definitive Genetic Variation [1]
Acne vulgaris DISKW8PI Strong Biomarker [2]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [3]
Asthma DISW9QNS Strong Biomarker [4]
Atopic dermatitis DISTCP41 Strong Genetic Variation [5]
Autoimmune disease DISORMTM Strong Genetic Variation [6]
Bipolar disorder DISAM7J2 Strong Genetic Variation [7]
Carcinoma DISH9F1N Strong Altered Expression [8]
Colitis DISAF7DD Strong Altered Expression [9]
Colon cancer DISVC52G Strong Altered Expression [10]
Colon carcinoma DISJYKUO Strong Altered Expression [10]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Dental caries DISRBCMD Strong Genetic Variation [11]
Depression DIS3XJ69 Strong Genetic Variation [6]
Gastritis DIS8G07K Strong Biomarker [12]
Gingivitis DISC8RMX Strong Altered Expression [13]
Human papillomavirus infection DISX61LX Strong Biomarker [14]
Lung carcinoma DISTR26C Strong Altered Expression [15]
Major depressive disorder DIS4CL3X Strong Genetic Variation [16]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [17]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [18]
Prostate carcinoma DISMJPLE Strong Altered Expression [19]
Prostate neoplasm DISHDKGQ Strong Biomarker [20]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [21]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [22]
Tuberculosis DIS2YIMD Strong Biomarker [6]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [23]
Ulcerative colitis DIS8K27O Strong Genetic Variation [24]
Vitiligo DISR05SL Strong Genetic Variation [25]
leukaemia DISS7D1V moderate Biomarker [26]
Leukemia DISNAKFL moderate Biomarker [26]
Neoplasm DISZKGEW moderate Biomarker [6]
Periodontitis DISI9JOI moderate Genetic Variation [27]
Prostate cancer DISF190Y moderate Altered Expression [19]
Stroke DISX6UHX moderate Genetic Variation [28]
Type-1 diabetes DIS7HLUB Disputed Biomarker [29]
Advanced cancer DISAT1Z9 Limited Altered Expression [30]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Biomarker [31]
Contact dermatitis DISQ3AU0 Limited Biomarker [32]
Cystic fibrosis DIS2OK1Q Limited Biomarker [33]
Hyperglycemia DIS0BZB5 Limited Altered Expression [34]
Liver cancer DISDE4BI Limited Biomarker [31]
Obesity DIS47Y1K Limited Biomarker [35]
Renal cell carcinoma DISQZ2X8 Limited Biomarker [36]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Beta-defensin 1 (DEFB1). [37]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Beta-defensin 1 (DEFB1). [38]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Beta-defensin 1 (DEFB1). [39]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Beta-defensin 1 (DEFB1). [40]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Beta-defensin 1 (DEFB1). [41]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Beta-defensin 1 (DEFB1). [42]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Beta-defensin 1 (DEFB1). [43]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Beta-defensin 1 (DEFB1). [44]
Menadione DMSJDTY Approved Menadione affects the expression of Beta-defensin 1 (DEFB1). [41]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Beta-defensin 1 (DEFB1). [45]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Beta-defensin 1 (DEFB1). [46]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Beta-defensin 1 (DEFB1). [46]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Beta-defensin 1 (DEFB1). [37]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Beta-defensin 1 (DEFB1). [47]
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⏷ Show the Full List of 14 Drug(s)

References

1 LTF and DEFB1 polymorphisms are associated with susceptibility toward chronic periodontitis development.Oral Dis. 2017 Oct;23(7):1001-1008. doi: 10.1111/odi.12689. Epub 2017 Jun 5.
2 Comparison of Efficacy of Doxycycline and Isotretinoin on Cutaneous Human Beta-Defensin-1 and -2 Levels in Acne Vulgaris.Indian J Dermatol. 2018 Sep-Oct;63(5):380-385. doi: 10.4103/ijd.IJD_402_16.
3 Association between DEFB1 gene haplotype and herpes viruses seroprevalence in children with acute lymphoblastic leukemia.Pediatr Hematol Oncol. 2009 Nov;26(8):573-82. doi: 10.3109/08880010903271705.
4 Airway -Defensin-1 Protein Is Elevated in COPD and Severe Asthma.Mediators Inflamm. 2015;2015:407271. doi: 10.1155/2015/407271. Epub 2015 Oct 19.
5 Hint for association of single nucleotide polymorphisms and haplotype in SPINK5 gene with atopic dermatitis in Koreans.Exp Dermatol. 2010 Dec;19(12):1048-53. doi: 10.1111/j.1600-0625.2010.01142.x.
6 Human -defensin 1 update: Potential clinical applications of the restless warrior.Int J Biochem Cell Biol. 2018 Nov;104:133-137. doi: 10.1016/j.biocel.2018.09.007. Epub 2018 Sep 17.
7 Neuroanatomical correlates of genetic risk for bipolar disorder: A voxel-based morphometry study in bipolar type I patients and healthy first degree relatives.J Affect Disord. 2015 Nov 1;186:110-8. doi: 10.1016/j.jad.2015.06.055. Epub 2015 Jul 26.
8 Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas.Lab Invest. 2003 Apr;83(4):501-5. doi: 10.1097/01.lab.0000063929.61760.f6.
9 Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis.Clin Exp Immunol. 2003 Jan;131(1):90-101. doi: 10.1046/j.1365-2249.2003.02035.x.
10 Expression of the human antimicrobial peptide -defensin-1 is repressed by the EGFR-ERK-MYC axis in colonic epithelial cells.Sci Rep. 2018 Dec 21;8(1):18043. doi: 10.1038/s41598-018-36387-z.
11 Association between genetic polymorphisms in DEFB1 and microRNA202 with caries in two groups of Brazilian children.Arch Oral Biol. 2018 Aug;92:1-7. doi: 10.1016/j.archoralbio.2018.04.010. Epub 2018 Apr 20.
12 Defensin-mRNA expression in the upper gastrointestinal tract is modulated in children with celiac disease and Helicobacter pylori-positive gastritis.J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):596-600. doi: 10.1097/MPG.0b013e3181cd26cd.
13 Gingival crevicular fluid levels of human beta-defensin 1 in individuals with and without chronic periodontitis.J Periodontal Res. 2018 Oct;53(5):736-742. doi: 10.1111/jre.12558. Epub 2018 Apr 23.
14 Human beta-defensin 1, 2 and 3 production by amniotic epithelial cells with respect to human papillomavirus (HPV) infection, HPV oncogenic potential and the mode of delivery.Microb Pathog. 2016 Aug;97:154-65. doi: 10.1016/j.micpath.2016.06.010. Epub 2016 Jun 8.
15 EGFR-targeting, -defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis.Acta Pharmacol Sin. 2018 Nov;39(11):1777-1786. doi: 10.1038/s41401-018-0069-8. Epub 2018 Jul 16.
16 Pharmacogenomics-Driven Prediction of Antidepressant Treatment Outcomes: A Machine-Learning Approach With Multi-trial Replication.Clin Pharmacol Ther. 2019 Oct;106(4):855-865. doi: 10.1002/cpt.1482. Epub 2019 Jun 29.
17 The -44 C/G (rs1800972) polymorphism of the -defensin 1 is associated with increased risk of developing type 2 diabetes mellitus.Mol Genet Genomic Med. 2019 Jan;7(1):e00509. doi: 10.1002/mgg3.509. Epub 2018 Dec 13.
18 Enediyne-activated, EGFR-targeted human -defensin 1 has therapeutic efficacy against non-small cell lung carcinoma.Lab Invest. 2018 Dec;98(12):1538-1548. doi: 10.1038/s41374-018-0109-5. Epub 2018 Sep 11.
19 DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells.PLoS One. 2016 Nov 11;11(11):e0166664. doi: 10.1371/journal.pone.0166664. eCollection 2016.
20 Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
21 Distinct innate immune gene expression profiles in non-melanoma skin cancer of immunocompetent and immunosuppressed patients.PLoS One. 2012;7(7):e40754. doi: 10.1371/journal.pone.0040754. Epub 2012 Jul 13.
22 Functional single-nucleotide polymorphisms in the DEFB1 gene are associated with systemic lupus erythematosus in Southern Brazilians.Lupus. 2012 May;21(6):625-31. doi: 10.1177/0961203312436858. Epub 2012 Feb 9.
23 Gingival crevicular fluid levels of human beta-defensin-1 in type 2 diabetes mellitus and periodontitis.Clin Oral Investig. 2018 Jun;22(5):2135-2140. doi: 10.1007/s00784-018-2469-z. Epub 2018 Apr 30.
24 DEFB1 gene 5' untranslated region (UTR) polymorphisms are marginally involved in inflammatory bowel disease in south Brazilians.Int J Immunogenet. 2014 Apr;41(2):138-42. doi: 10.1111/iji.12089. Epub 2013 Sep 12.
25 Association of human beta-defensin 1 gene polymorphisms with nonsegmental vitiligo.Clin Exp Dermatol. 2019 Apr;44(3):277-282. doi: 10.1111/ced.13697. Epub 2018 Jun 20.
26 Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor.J Med Chem. 2018 Jul 26;61(14):6110-6120. doi: 10.1021/acs.jmedchem.8b00483. Epub 2018 Jul 17.
27 Association between Periodontitis and Gene polymorphisms of hBD-1 and CD14: a meta-analysis.Arch Oral Biol. 2019 Aug;104:141-149. doi: 10.1016/j.archoralbio.2019.05.029. Epub 2019 Jun 1.
28 Genetic polymorphisms of human -defensins in patients with ischemic stroke.Acta Neurol Scand. 2012 Aug;126(2):109-15. doi: 10.1111/j.1600-0404.2011.01613.x. Epub 2011 Nov 2.
29 Characterization of host defense molecules in the human pancreas.Islets. 2019;11(4):89-101. doi: 10.1080/19382014.2019.1585165. Epub 2019 Jun 26.
30 Human Beta Defensins and Cancer: Contradictions and Common Ground.Front Oncol. 2019 May 3;9:341. doi: 10.3389/fonc.2019.00341. eCollection 2019.
31 -defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development.Sci Rep. 2017 Oct 17;7(1):13404. doi: 10.1038/s41598-017-13332-0.
32 Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin modelDevelopment of the SENS-IS assay. Toxicol In Vitro. 2015 Jun;29(4):787-802.
33 A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients.Clin Chem Lab Med. 2011 Jan;49(1):49-54. doi: 10.1515/CCLM.2011.023. Epub 2010 Nov 16.
34 Glucose regulation of beta-defensin-1 mRNA in human renal cells.Biochem Biophys Res Commun. 2007 Feb 9;353(2):318-23. doi: 10.1016/j.bbrc.2006.12.037. Epub 2006 Dec 14.
35 Nucleotide sequence and expression of rat beta-defensin-1: its significance in diabetic rodent models.Nephron. 2001 May;88(1):65-70. doi: 10.1159/000045961.
36 Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma.Cancer Res. 2006 Sep 1;66(17):8542-9. doi: 10.1158/0008-5472.CAN-06-0294.
37 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.
38 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
39 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
40 Decreased urinary beta-defensin-1 expression as a biomarker of response to arsenic. Toxicol Sci. 2008 Nov;106(1):74-82. doi: 10.1093/toxsci/kfn104. Epub 2008 May 28.
41 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
42 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
43 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
44 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.
45 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
46 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
47 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.