Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5PBGJ)

DOT Name Dermcidin (DCD)
Synonyms EC 3.4.-.-; Preproteolysin
Gene Name DCD
Related Disease
Esophageal cancer ( )
Rabies ( )
Acne vulgaris ( )
Atopic dermatitis ( )
Attention deficit hyperactivity disorder ( )
Autism spectrum disorder ( )
Breast cancer ( )
Breast carcinoma ( )
Cerebral palsy ( )
Congestive heart failure ( )
Early-onset anterior polar cataract ( )
Hepatocellular carcinoma ( )
Hidradenitis suppurativa ( )
Isolated cleft palate ( )
Lichen planus ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Obstructive sleep apnea ( )
Pancreatic cancer ( )
Pneumonia ( )
Pneumonitis ( )
Prostate neoplasm ( )
Skin disease ( )
Inclusion body myositis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Anhidrosis ( )
Dental caries ( )
Gastric cancer ( )
Liver cirrhosis ( )
Non-insulin dependent diabetes ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
UniProt ID
DCD_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2KSG; 2NDK; 2YMK; 6SHK
EC Number
3.4.-.-
Pfam ID
PF15291
Sequence
MRFMTLLFLTALAGALVCAYDPEAASAPGSGNPCHEASAAQKENAGEDPGLARQAPKPRK
QRSSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
Function
[DCD-1]: Found in sweat, has an antimicrobial activity during early bacterial colonization. The secreted peptide assembles into homohexameric complexes that can associate with and also insert into pathogen membranes. Once inserted in bacteria membranes forms anion channels probably altering the transmembrane potential essential for bacterial survival. Highly effective against E.coli, E.faecalis, S.aureus and C.albicans. Optimal pH and salt concentration resemble the conditions in sweat. Also exhibits proteolytic activity, cleaving on the C-terminal side of Arg and, to a lesser extent, Lys residues ; [Survival-promoting peptide]: Promotes survival of neurons and displays phosphatase activity. It may bind IgG.
Tissue Specificity Detected in urine (at protein level) . Constitutively expressed in eccrine sweat gland cells (at protein level). Secreted into the sweat at a concentration of 1-10 micrograms/ml.
Reactome Pathway
Antimicrobial peptides (R-HSA-6803157 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Esophageal cancer DISGB2VN Definitive Altered Expression [1]
Rabies DISSC4V5 Definitive Biomarker [2]
Acne vulgaris DISKW8PI Strong Altered Expression [3]
Atopic dermatitis DISTCP41 Strong Altered Expression [4]
Attention deficit hyperactivity disorder DISL8MX9 Strong Biomarker [5]
Autism spectrum disorder DISXK8NV Strong Altered Expression [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Cerebral palsy DIS82ODL Strong Biomarker [8]
Congestive heart failure DIS32MEA Strong Biomarker [9]
Early-onset anterior polar cataract DISTOPIY Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Hidradenitis suppurativa DIS3ZNAK Strong Altered Expression [12]
Isolated cleft palate DISV80CD Strong Biomarker [8]
Lichen planus DISRPMMS Strong Biomarker [13]
Liver cancer DISDE4BI Strong Biomarker [14]
Lung cancer DISCM4YA Strong Biomarker [15]
Lung carcinoma DISTR26C Strong Biomarker [15]
Neoplasm DISZKGEW Strong Biomarker [16]
Obstructive sleep apnea DIS0SVD1 Strong Biomarker [17]
Pancreatic cancer DISJC981 Strong Biomarker [18]
Pneumonia DIS8EF3M Strong Genetic Variation [10]
Pneumonitis DIS88E0K Strong Biomarker [10]
Prostate neoplasm DISHDKGQ Strong Biomarker [19]
Skin disease DISDW8R6 Strong Biomarker [20]
Inclusion body myositis DISZXXG5 moderate Biomarker [21]
Prostate cancer DISF190Y moderate Genetic Variation [22]
Prostate carcinoma DISMJPLE moderate Genetic Variation [22]
Anhidrosis DISYLSTC Disputed Altered Expression [23]
Dental caries DISRBCMD Limited Biomarker [24]
Gastric cancer DISXGOUK Limited Biomarker [25]
Liver cirrhosis DIS4G1GX Limited Altered Expression [11]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [26]
Stomach cancer DISKIJSX Limited Biomarker [25]
Type-1/2 diabetes DISIUHAP Limited Biomarker [27]
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⏷ Show the Full List of 35 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Dermcidin (DCD). [28]
Clozapine DMFC71L Approved Clozapine decreases the expression of Dermcidin (DCD). [30]
Benzatropine DMF7EXL Approved Benzatropine decreases the expression of Dermcidin (DCD). [30]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Dermcidin (DCD). [32]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Aspirin DM672AH Approved Aspirin decreases the secretion of Dermcidin (DCD). [29]
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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 decreases the methylation of Dermcidin (DCD). [31]
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References

1 Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy.Br J Cancer. 2006 Mar 13;94(5):731-6. doi: 10.1038/sj.bjc.6602989.
2 Transmission of rabies through solid organ transplantation: a notable problem in China.BMC Infect Dis. 2018 Jun 14;18(1):273. doi: 10.1186/s12879-018-3112-y.
3 Plasma dermcidin levels in acne patients, and the effect of isotretinoin treatment on dermcidin levels.Dermatol Ther. 2019 Sep;32(5):e13044. doi: 10.1111/dth.13044. Epub 2019 Aug 20.
4 Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.J Immunol. 2005 Jun 15;174(12):8003-10. doi: 10.4049/jimmunol.174.12.8003.
5 ADHD and poor motor performance from a family genetic perspective.J Am Acad Child Adolesc Psychiatry. 2009 Jan;48(1):25-34. doi: 10.1097/CHI.0b013e31818b1ca2.
6 Interpersonal Synchronization, Motor Coordination, and Control Are Impaired During a Dynamic Imitation Task in Children With Autism Spectrum Disorder.Front Psychol. 2018 Sep 3;9:1467. doi: 10.3389/fpsyg.2018.01467. eCollection 2018.
7 Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling.BMC Cancer. 2015 Feb 19;15:70. doi: 10.1186/s12885-015-1022-6.
8 Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks.Int J Oncol. 2011 Sep;39(3):709-18. doi: 10.3892/ijo.2011.1064. Epub 2011 Jun 3.
9 Is there a human homologue to the murine proteolysis-inducing factor?.Clin Cancer Res. 2007 Sep 1;13(17):4984-92. doi: 10.1158/1078-0432.CCR-07-0946.
10 Rates of hospitalization for community-acquired pneumonia among US adults: A systematic review.Vaccine. 2020 Jan 22;38(4):741-751. doi: 10.1016/j.vaccine.2019.10.101. Epub 2019 Dec 13.
11 The Role of Dermcidin in the Diagnosis and Staging of Hepatocellular Carcinoma.Genet Test Mol Biomarkers. 2018 Apr;22(4):218-223. doi: 10.1089/gtmb.2017.0230. Epub 2018 Mar 16.
12 Transcriptome patterns in hidradenitis suppurativa: support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis.Clin Exp Dermatol. 2019 Dec;44(8):882-892. doi: 10.1111/ced.13959. Epub 2019 Apr 24.
13 Leakage of sweat into the dermo-epidermal junction as a possible trigger for lichen planus lesion development.Arch Dermatol Res. 2019 Jan;311(1):71-82. doi: 10.1007/s00403-018-1882-0. Epub 2018 Dec 3.
14 Evaluation of plasma carcinogenic markers in rat hepatic tumors models induced by rat hepatoma N1-S1 cells and benzo[a]pyrene.Arch Pharm Res. 2010 Feb;33(2):247-55. doi: 10.1007/s12272-010-0210-9. Epub 2010 Feb 24.
15 Mass Spectrometry Analysis of the Exhaled Breath Condensate and Proposal of Dermcidin and S100A9 as Possible Markers for Lung Cancer Prognosis.Lung. 2019 Aug;197(4):523-531. doi: 10.1007/s00408-019-00238-z. Epub 2019 May 21.
16 Are tumoral factors responsible for host tissue wasting in cancer cachexia?.Future Oncol. 2010 Apr;6(4):503-13. doi: 10.2217/fon.10.20.
17 Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients.Sleep Med. 2019 Dec;64:92-100. doi: 10.1016/j.sleep.2019.07.002. Epub 2019 Jul 8.
18 Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3.FASEB J. 2001 Mar;15(3):562-4. doi: 10.1096/fj.00-0534fje. Epub 2001 Jan 19.
19 Dermcidin expression confers a survival advantage in prostate cancer cells subjected to oxidative stress or hypoxia.Prostate. 2007 Sep 1;67(12):1308-17. doi: 10.1002/pros.20618.
20 Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions.Br J Dermatol. 2004 Sep;151(3):534-9. doi: 10.1111/j.1365-2133.2004.06081.x.
21 Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM.Neurology. 2001 Nov 13;57(9):1561-5. doi: 10.1212/wnl.57.9.1561.
22 Insulin resistance in prostate cancer patients and predisposing them to acute ischemic heart disease.Biosci Rep. 2019 Jul 29;39(7):BSR20182313. doi: 10.1042/BSR20182313. Print 2019 Jul 31.
23 Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.J Eur Acad Dermatol Venereol. 2017 Dec;31(12):2097-2103. doi: 10.1111/jdv.14443. Epub 2017 Jul 20.
24 Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2.EBioMedicine. 2017 Dec;26:38-46. doi: 10.1016/j.ebiom.2017.11.019. Epub 2017 Nov 22.
25 Dermcidin as a novel binding protein of lncRNA STCAT3 and its effect on prognosis in gastric cancer.Oncol Rep. 2018 Nov;40(5):2854-2863. doi: 10.3892/or.2018.6673. Epub 2018 Aug 24.
26 Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.J Hum Genet. 2012 May;57(5):305-10. doi: 10.1038/jhg.2012.21. Epub 2012 Mar 1.
27 The role of Dermcidin isoform-2 in the occurrence and severity of Diabetes.Sci Rep. 2017 Aug 15;7(1):8252. doi: 10.1038/s41598-017-07958-3.
28 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.
29 Moderation of the platelet releasate response by aspirin. Blood. 2007 Jun 1;109(11):4786-92. doi: 10.1182/blood-2006-07-038539. Epub 2007 Feb 15.
30 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
31 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.
32 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.