Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8RWY64)

DOT Name Beta-defensin 103 (DEFB103B)
Synonyms Beta-defensin 3; BD-3; DEFB-3; HBD3; hBD-3; Defensin, beta 103; Defensin-like protein
Gene Name DEFB103B
Related Disease
Bacteremia ( )
Advanced cancer ( )
Amyloidosis ( )
Appendicitis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Atopic dermatitis ( )
Autoimmune disease ( )
Bacterial infection ( )
Candidiasis ( )
Cervical cancer ( )
Cervical carcinoma ( )
Chorioamnionitis ( )
Coeliac disease ( )
Colon cancer ( )
Colon carcinoma ( )
Esophageal candidiasis ( )
Growth delay due to insulin-like growth factor type 1 deficiency ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Idiopathic inflammatory myopathy ( )
Inflammatory bowel disease ( )
Influenza ( )
Multiple sclerosis ( )
Mycosis fungoides ( )
Neoplasm ( )
Oropharyngeal cancer ( )
Oropharyngeal carcinoma ( )
Polymyositis ( )
Squamous cell carcinoma ( )
Tuberculosis ( )
Ulcerative colitis ( )
Gastritis ( )
Gingivitis ( )
Periodontitis ( )
Bacterial vaginosis ( )
Dental caries ( )
Eosinophilic esophagitis ( )
Non-insulin dependent diabetes ( )
UniProt ID
D103A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1KJ6
Pfam ID
PF00711
Sequence
MRIHYLLFALLFLFLVPVPGHGGIINTLQKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGR
KCCRRKK
Function
Exhibits antimicrobial activity against Gram-positive bacteria S.aureus and S.pyogenes, Gram-negative bacteria P.aeruginosa and E.coli and the yeast C.albicans. Kills multiresistant S.aureus and vancomycin-resistant E.faecium. No significant hemolytic activity was observed.
Tissue Specificity
Highly expressed in skin and tonsils, and to a lesser extent in trachea, uterus, kidney, thymus, adenoid, pharynx and tongue. Low expression in salivary gland, bone marrow, colon, stomach, polyp and larynx. No expression in small intestine.
KEGG Pathway
NOD-like receptor sig.ling pathway (hsa04621 )
Staphylococcus aureus infection (hsa05150 )
Reactome Pathway
Defensins (R-HSA-1461973 )
Beta defensins (R-HSA-1461957 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bacteremia DIS6N9RZ Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Amyloidosis DISHTAI2 Strong Biomarker [3]
Appendicitis DIS4GOLF Strong Altered Expression [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Atopic dermatitis DISTCP41 Strong Altered Expression [6]
Autoimmune disease DISORMTM Strong Biomarker [7]
Bacterial infection DIS5QJ9S Strong Biomarker [8]
Candidiasis DISIRYMU Strong Altered Expression [9]
Cervical cancer DISFSHPF Strong Biomarker [10]
Cervical carcinoma DIST4S00 Strong Biomarker [10]
Chorioamnionitis DISL1D9U Strong Altered Expression [11]
Coeliac disease DISIY60C Strong Biomarker [12]
Colon cancer DISVC52G Strong Altered Expression [13]
Colon carcinoma DISJYKUO Strong Altered Expression [13]
Esophageal candidiasis DISV4PM2 Strong Altered Expression [9]
Growth delay due to insulin-like growth factor type 1 deficiency DISHA2HH Strong Altered Expression [14]
Head and neck cancer DISBPSQZ Strong Altered Expression [15]
Head and neck carcinoma DISOU1DS Strong Altered Expression [15]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [16]
Idiopathic inflammatory myopathy DISGB1BZ Strong Altered Expression [3]
Inflammatory bowel disease DISGN23E Strong Biomarker [17]
Influenza DIS3PNU3 Strong Biomarker [18]
Multiple sclerosis DISB2WZI Strong Biomarker [19]
Mycosis fungoides DIS62RB8 Strong Altered Expression [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Oropharyngeal cancer DISDAMTJ Strong Altered Expression [15]
Oropharyngeal carcinoma DIS7K3AI Strong Altered Expression [15]
Polymyositis DIS5DHFP Strong Altered Expression [3]
Squamous cell carcinoma DISQVIFL Strong Biomarker [22]
Tuberculosis DIS2YIMD Strong Altered Expression [23]
Ulcerative colitis DIS8K27O Strong Biomarker [24]
Gastritis DIS8G07K moderate Biomarker [25]
Gingivitis DISC8RMX moderate Biomarker [26]
Periodontitis DISI9JOI moderate Altered Expression [27]
Bacterial vaginosis DISK2MZ2 Limited Altered Expression [28]
Dental caries DISRBCMD Limited Biomarker [29]
Eosinophilic esophagitis DISR8WSB Limited Altered Expression [30]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [31]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Beta-defensin 103 (DEFB103B). [32]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Beta-defensin 103 (DEFB103B). [33]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Beta-defensin 103 (DEFB103B). [34]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Beta-defensin 103 (DEFB103B). [35]
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References

1 Genetic variability in beta-defensins is not associated with susceptibility to Staphylococcus aureus bacteremia.PLoS One. 2012;7(2):e32315. doi: 10.1371/journal.pone.0032315. Epub 2012 Feb 22.
2 Human Beta Defensins and Cancer: Contradictions and Common Ground.Front Oncol. 2019 May 3;9:341. doi: 10.3389/fonc.2019.00341. eCollection 2019.
3 Human -defensin-3 correlates with muscle fibre degeneration in idiopathic inflammatory myopathies.Innate Immun. 2014 Jan;20(1):49-60. doi: 10.1177/1753425913481820. Epub 2013 Apr 22.
4 Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis.Innate Immun. 2015 Jan;21(1):30-41. doi: 10.1177/1753425913515033. Epub 2013 Dec 11.
5 Human -Defensin 3 Reduces TNF--Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells.Mediators Inflamm. 2017;2017:8529542. doi: 10.1155/2017/8529542. Epub 2017 Feb 28.
6 Activity, expression and genetic variation of canine -defensin 103: a multifunctional antimicrobial peptide in the skin of domestic dogs.J Innate Immun. 2012;4(3):248-59. doi: 10.1159/000334566. Epub 2012 Jan 19.
7 Human -Defensin 3 [corrected] Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid.PLoS Genet. 2015 Dec 8;11(12):e1005673. doi: 10.1371/journal.pgen.1005673. eCollection 2015 Dec.
8 Increased expression of hepcidin and toll-like receptors 8 and 10 in viral keratitis.Cornea. 2011 Aug;30(8):899-904. doi: 10.1097/ICO.0b013e31820126e5.
9 IL-1 and ADAM17 are central regulators of -defensin expression in Candida esophagitis.Am J Physiol Gastrointest Liver Physiol. 2011 Apr;300(4):G547-53. doi: 10.1152/ajpgi.00251.2010. Epub 2011 Jan 13.
10 Human beta-defensin 3 contributes to the carcinogenesis of cervical cancer via activation of NF-B signaling.Oncotarget. 2016 Nov 15;7(46):75902-75913. doi: 10.18632/oncotarget.12426.
11 Increased production of beta-defensin 3 (hBD-3) by human amniotic epithelial cells (HAEC) after activation of toll-like receptor 4 in chorioamnionitis.Inflamm Res. 2008;57 Suppl 1:S67-8. doi: 10.1007/s00011-007-0633-z.
12 Low expression of human beta-defensin 1 in duodenum of celiac patients is partially restored by a gluten-free diet.Clin Chem Lab Med. 2010 Apr;48(4):489-92. doi: 10.1515/CCLM.2010.098.
13 Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.PLoS One. 2015 Jun 3;10(6):e0126868. doi: 10.1371/journal.pone.0126868. eCollection 2015.
14 IGF-1 deficiency in combination with a low basic hBD-2 and hBD-3 gene expression might counteract malignant transformation in pleomorphic adenomas in vitro.Cancer Invest. 2012 Feb;30(2):106-13. doi: 10.3109/07357907.2011.640651.
15 Human papillomavirus oncogenic E6 protein regulates human -defensin 3 (hBD3) expression via the tumor suppressor protein p53.Oncotarget. 2016 May 10;7(19):27430-44. doi: 10.18632/oncotarget.8443.
16 Human -defensin 3 promotes NF-B-mediated CCR7 expression and anti-apoptotic signals in squamous cell carcinoma of the head and neck.Carcinogenesis. 2011 Feb;32(2):168-74. doi: 10.1093/carcin/bgq236. Epub 2010 Nov 11.
17 beta-Defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis.Clin Exp Immunol. 2004 Aug;137(2):379-85. doi: 10.1111/j.1365-2249.2004.02543.x.
18 A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia.Hum Mutat. 2011 Jul;32(7):743-50. doi: 10.1002/humu.21491. Epub 2011 May 5.
19 The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.Iran J Allergy Asthma Immunol. 2019 Jun 8;18(3):230-250. doi: 10.18502/ijaai.v18i3.1117.
20 Expression of human beta-defensins in patients with mycosis fungoides.Arch Dermatol Res. 2007 Jul;299(4):221-4. doi: 10.1007/s00403-007-0749-6. Epub 2007 Apr 6.
21 Human -defensin 3 contains an oncolytic motif that binds PI(4,5)P2 to mediate tumour cell permeabilisation.Oncotarget. 2016 Jan 12;7(2):2054-69. doi: 10.18632/oncotarget.6520.
22 Nitric oxide-producing myeloid-derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas.J Invest Dermatol. 2012 Nov;132(11):2642-51. doi: 10.1038/jid.2012.190. Epub 2012 Jun 21.
23 Evidence that changes in antimicrobial peptides during tuberculosis are related to disease severity, clinical presentation, specific therapy and levels of immune-endocrine mediators.Cytokine. 2020 Feb;126:154913. doi: 10.1016/j.cyto.2019.154913. Epub 2019 Nov 12.
24 Human -defensin 3 peptide is increased and redistributed in Crohn's ileitis.Inflamm Bowel Dis. 2013 Apr;19(5):942-53. doi: 10.1097/MIB.0b013e318280b11a.
25 Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues.World J Gastroenterol. 2006 Sep 28;12(36):5793-7. doi: 10.3748/wjg.v12.i36.5793.
26 Gingival tissue human beta-defensin levels in relation to infection and inflammation.J Clin Periodontol. 2020 Mar;47(3):309-318. doi: 10.1111/jcpe.13227. Epub 2020 Jan 7.
27 EB 2017 Article: Changes in advanced glycation end products, beta-defensin-3, and interleukin-17 during diabetic periodontitis development in rhesus monkeys.Exp Biol Med (Maywood). 2018 May;243(8):684-694. doi: 10.1177/1535370218766512. Epub 2018 Mar 27.
28 Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection.PLoS One. 2019 Apr 26;14(4):e0216049. doi: 10.1371/journal.pone.0216049. eCollection 2019.
29 The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants.J Microbiol. 2017 Oct;55(10):830-836. doi: 10.1007/s12275-017-7362-y. Epub 2017 Sep 28.
30 Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.Allergy. 2015 Apr;70(4):443-52. doi: 10.1111/all.12570. Epub 2015 Jan 26.
31 Overexpressions of hBD-2, hBD-3, and hCAP18/LL-37 in Gingiva of Diabetics with Periodontitis.Immunobiology. 2015 Nov;220(11):1219-26. doi: 10.1016/j.imbio.2015.06.013. Epub 2015 Jun 10.
32 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.
33 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
34 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.
35 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.