Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLSTT2B)

DOT Name Matrix metalloproteinase-19 (MMP19)
Synonyms MMP-19; EC 3.4.24.-; Matrix metalloproteinase RASI; Matrix metalloproteinase-18; MMP-18
Gene Name MMP19
Related Disease
Arthropathy ( )
Respiratory syncytial virus infection ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Astrocytoma ( )
Chronic kidney disease ( )
Colitis ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Glioblastoma multiforme ( )
Inflammatory bowel disease ( )
Keloid ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Malignant glioma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Psoriasis ( )
Pulmonary fibrosis ( )
Skin cancer ( )
Skin neoplasm ( )
Familial cavitary optic disk anomaly ( )
Advanced cancer ( )
Asthma ( )
Gallbladder carcinoma ( )
Nasopharyngeal carcinoma ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
UniProt ID
MMP19_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.4.24.-
Pfam ID
PF00045 ; PF00413 ; PF01471
Sequence
MNCQQLWLGFLLPMTVSGRVLGLAEVAPVDYLSQYGYLQKPLEGSNNFKPEDITEALRAF
QEASELPVSGQLDDATRARMRQPRCGLEDPFNQKTLKYLLLGRWRKKHLTFRILNLPSTL
PPHTARAALRQAFQDWSNVAPLTFQEVQAGAADIRLSFHGRQSSYCSNTFDGPGRVLAHA
DIPELGSVHFDEDEFWTEGTYRGVNLRIIAAHEVGHALGLGHSRYSQALMAPVYEGYRPH
FKLHPDDVAGIQALYGKKSPVIRDEEEEETELPTVPPVPTEPSPMPDPCSSELDAMMLGP
RGKTYAFKGDYVWTVSDSGPGPLFRVSALWEGLPGNLDAAVYSPRTQWIHFFKGDKVWRY
INFKMSPGFPKKLNRVEPNLDAALYWPLNQKVFLFKGSGYWQWDELARTDFSSYPKPIKG
LFTGVPNQPSAAMSWQDGRVYFFKGKVYWRLNQQLRVEKGYPRNISHNWMHCRPRTIDTT
PSGGNTTPSGTGITLDTTLSATETTFEY
Function
Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin.
Tissue Specificity
Expressed in mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart and blood vessel walls. Not detected in brain and peripheral blood leukocytes. Also expressed in the synovial fluid of normal and rheumatoid patients .
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )
Collagen degradation (R-HSA-1442490 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthropathy DISVEERK Definitive Altered Expression [1]
Respiratory syncytial virus infection DIS7FWHY Definitive Altered Expression [2]
Adenocarcinoma DIS3IHTY Strong Biomarker [3]
Adult glioblastoma DISVP4LU Strong Biomarker [4]
Astrocytoma DISL3V18 Strong Altered Expression [4]
Chronic kidney disease DISW82R7 Strong Biomarker [5]
Colitis DISAF7DD Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [7]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [8]
Glioblastoma multiforme DISK8246 Strong Biomarker [4]
Inflammatory bowel disease DISGN23E Strong Biomarker [6]
Keloid DISV09JY Strong Biomarker [9]
Lung cancer DISCM4YA Strong Altered Expression [10]
Lung carcinoma DISTR26C Strong Altered Expression [10]
Lung neoplasm DISVARNB Strong Altered Expression [10]
Malignant glioma DISFXKOV Strong Biomarker [11]
Neoplasm DISZKGEW Strong Altered Expression [10]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [10]
Obesity DIS47Y1K Strong Biomarker [12]
Osteoarthritis DIS05URM Strong Altered Expression [13]
Ovarian cancer DISZJHAP Strong Altered Expression [8]
Ovarian neoplasm DISEAFTY Strong Altered Expression [8]
Psoriasis DIS59VMN Strong Altered Expression [14]
Pulmonary fibrosis DISQKVLA Strong Biomarker [15]
Skin cancer DISTM18U Strong Biomarker [12]
Skin neoplasm DIS16DDV Strong Biomarker [12]
Familial cavitary optic disk anomaly DIS1W9WJ Supportive Autosomal dominant [16]
Advanced cancer DISAT1Z9 Limited Altered Expression [17]
Asthma DISW9QNS Limited Biomarker [18]
Gallbladder carcinoma DISD6ACL Limited Altered Expression [19]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [20]
Rheumatoid arthritis DISTSB4J Limited Biomarker [12]
Squamous cell carcinoma DISQVIFL Limited Biomarker [21]
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⏷ Show the Full List of 33 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
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Matrix metalloproteinase-19 (MMP19). [22]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Matrix metalloproteinase-19 (MMP19). [23]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Matrix metalloproteinase-19 (MMP19). [25]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Matrix metalloproteinase-19 (MMP19). [26]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Matrix metalloproteinase-19 (MMP19). [27]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Matrix metalloproteinase-19 (MMP19). [28]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Matrix metalloproteinase-19 (MMP19). [29]
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⏷ Show the Full List of 7 Drug(s)
1 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 Matrix metalloproteinase-19 (MMP19). [24]
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References

1 The matrix metalloproteinase RASI-1 is expressed in synovial blood vessels of a rheumatoid arthritis patient.Immunol Lett. 1997 Jun 1;57(1-3):83-8. doi: 10.1016/s0165-2478(97)00057-6.
2 Downregulation of matrix metalloproteinase?9 induced by respiratory syncytial viral infection affects the interaction between epithelial cells and fibroblasts.Mol Med Rep. 2016 Jan;13(1):167-73. doi: 10.3892/mmr.2015.4518. Epub 2015 Nov 6.
3 Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease.J Cutan Pathol. 2004 Aug;31(7):483-91. doi: 10.1111/j.0303-6987.2004.00211.x.
4 Matrix metalloproteinase-19 is highly expressed in astroglial tumors and promotes invasion of glioma cells.J Neuropathol Exp Neurol. 2010 Mar;69(3):215-23. doi: 10.1097/NEN.0b013e3181ce9f67.
5 Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?.Nefrologia (Engl Ed). 2020 Jan-Feb;40(1):38-45. doi: 10.1016/j.nefro.2019.02.013. Epub 2019 Jun 10.
6 MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function.Mucosal Immunol. 2016 Jul;9(4):974-85. doi: 10.1038/mi.2015.117. Epub 2015 Nov 11.
7 High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer.BMC Cancer. 2019 May 14;19(1):448. doi: 10.1186/s12885-019-5673-6.
8 Matrix Metalloproteinase Expressions Play Important role in Prediction of Ovarian Cancer Outcome.Sci Rep. 2019 Aug 12;9(1):11677. doi: 10.1038/s41598-019-47871-5.
9 Identification of biomarkers involved in differential profiling of hypertrophic and keloid scars versus normal skin.Arch Dermatol Res. 2015 Mar;307(2):115-33. doi: 10.1007/s00403-014-1512-4. Epub 2014 Oct 17.
10 Matrix metalloproteinase-19 promotes metastatic behavior in vitro and is associated with increased mortality in non-small cell lung cancer.Am J Respir Crit Care Med. 2014 Oct 1;190(7):780-90. doi: 10.1164/rccm.201310-1903OC.
11 Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas.Neurosci Res. 2008 Jan;60(1):40-9. doi: 10.1016/j.neures.2007.09.009. Epub 2007 Sep 29.
12 Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice.Mol Cell Biol. 2004 Jun;24(12):5304-13. doi: 10.1128/MCB.24.12.5304-5313.2004.
13 MicroRNA-193b-3p regulates matrix metalloproteinase 19 expression in interleukin-1-induced human chondrocytes.J Cell Biochem. 2018 Jun;119(6):4775-4782. doi: 10.1002/jcb.26669. Epub 2018 Mar 1.
14 Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation.J Invest Dermatol. 2003 Nov;121(5):989-96. doi: 10.1046/j.1523-1747.2003.12526.x.
15 Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and humans.Am J Respir Crit Care Med. 2012 Oct 15;186(8):752-62. doi: 10.1164/rccm.201202-0302OC. Epub 2012 Aug 2.
16 Heterozygous triplication of upstream regulatory sequences leads to dysregulation of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly. Hum Mutat. 2015 Mar;36(3):369-78. doi: 10.1002/humu.22754.
17 Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages.Int J Oncol. 2012 Jul;41(1):260-6. doi: 10.3892/ijo.2012.1441. Epub 2012 Apr 19.
18 Matrix metalloproteinase-19 deficiency promotes tenascin-C accumulation and allergen-induced airway inflammation.Am J Respir Cell Mol Biol. 2010 Sep;43(3):286-95. doi: 10.1165/rcmb.2008-0426OC. Epub 2009 Oct 20.
19 Loss of NDRG2 promotes epithelial-mesenchymal transition of gallbladder carcinoma cells through MMP-19-mediated Slug expression.J Hepatol. 2015 Dec;63(6):1429-39. doi: 10.1016/j.jhep.2015.08.007. Epub 2015 Aug 17.
20 Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.Mol Cancer Ther. 2013 Oct;12(10):2157-66. doi: 10.1158/1535-7163.MCT-12-1190. Epub 2013 Aug 16.
21 Matrix metalloproteinase-19 is a predictive marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.Int J Biol Markers. 2007 Oct-Dec;22(4):265-73.
22 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
23 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
24 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.
25 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
26 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
27 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
28 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
29 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.