Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16S5S3)

DOT Name Matrix metalloproteinase-20 (MMP20)
Synonyms MMP-20; EC 3.4.24.-; Enamel metalloproteinase; Enamelysin
Gene Name MMP20
Related Disease
Chronic kidney disease ( )
Chronic renal failure ( )
Advanced cancer ( )
Amelogenesis imperfecta hypomaturation type 2A2 ( )
Anal intraepithelial neoplasia ( )
Dental caries ( )
Dentin dysplasia ( )
Dentinogenesis imperfecta ( )
Graves disease ( )
Lung neoplasm ( )
Neoplasm ( )
Oral cancer ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Uterine cervix neoplasm ( )
Age-related macular degeneration ( )
Laryngeal squamous cell carcinoma ( )
Neuroblastoma ( )
Amelogenesis imperfecta type 2 ( )
Amelogenesis imperfecta ( )
Rheumatoid arthritis ( )
UniProt ID
MMP20_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2JSD
EC Number
3.4.24.-
Pfam ID
PF00045 ; PF00413 ; PF01471
Sequence
MKVLPASGLAVFLIMALKFSTAAPSLVAASPRTWRNNYRLAQAYLDKYYTNKEGHQIGEM
VARGSNSMIRKIKELQAFFGLQVTGKLDQTTMNVIKKPRCGVPDVANYRLFPGEPKWKKN
TLTYRISKYTPSMSSVEVDKAVEMALQAWSSAVPLSFVRINSGEADIMISFENGDHGDSY
PFDGPRGTLAHAFAPGEGLGGDTHFDNAEKWTMGTNGFNLFTVAAHEFGHALGLAHSTDP
SALMYPTYKYKNPYGFHLPKDDVKGIQALYGPRKVFLGKPTLPHAPHHKPSIPDLCDSSS
SFDAVTMLGKELLLFKDRIFWRRQVHLRTGIRPSTITSSFPQLMSNVDAAYEVAERGTAY
FFKGPHYWITRGFQMQGPPRTIYDFGFPRHVQQIDAAVYLREPQKTLFFVGDEYYSYDER
KRKMEKDYPKNTEEEFSGVNGQIDAAVELNGYIYFFSGPKTYKYDTEKEDVVSVVKSSSW
IGC
Function
Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation. Cleaves aggrecan at the '360-Asn-|-Phe-361' site.
Tissue Specificity Expressed specifically in the enamel organ.
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )
Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090 )
Collagen degradation (R-HSA-1442490 )

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic kidney disease DISW82R7 Definitive Genetic Variation [1]
Chronic renal failure DISGG7K6 Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Amelogenesis imperfecta hypomaturation type 2A2 DIS951IF Strong Autosomal recessive [3]
Anal intraepithelial neoplasia DISJ0JW3 Strong Biomarker [4]
Dental caries DISRBCMD Strong Biomarker [5]
Dentin dysplasia DISCGIX8 Strong Biomarker [3]
Dentinogenesis imperfecta DISJLZU4 Strong Biomarker [6]
Graves disease DISU4KOQ Strong Genetic Variation [7]
Lung neoplasm DISVARNB Strong Altered Expression [8]
Neoplasm DISZKGEW Strong Biomarker [8]
Oral cancer DISLD42D Strong Biomarker [2]
Thyroid cancer DIS3VLDH Strong Altered Expression [9]
Thyroid gland carcinoma DISMNGZ0 Strong Altered Expression [9]
Uterine cervix neoplasm DIS0BYVV Strong Altered Expression [9]
Age-related macular degeneration DIS0XS2C moderate Biomarker [10]
Laryngeal squamous cell carcinoma DIS9UUVF moderate Biomarker [11]
Neuroblastoma DISVZBI4 moderate Genetic Variation [12]
Amelogenesis imperfecta type 2 DISX8NN4 Supportive Autosomal recessive [13]
Amelogenesis imperfecta DISGYR9E Limited Genetic Variation [14]
Rheumatoid arthritis DISTSB4J Limited Biomarker [15]
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⏷ Show the Full List of 21 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Matrix metalloproteinase-20 (MMP20). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Matrix metalloproteinase-20 (MMP20). [17]
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References

1 Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms.J Am Soc Nephrol. 2018 May;29(5):1513-1524. doi: 10.1681/ASN.2017101099. Epub 2018 Mar 15.
2 DSPP-MMP20 gene silencing downregulates cancer stem cell markers in human oral cancer cells.Cell Mol Biol Lett. 2018 Jul 11;23:30. doi: 10.1186/s11658-018-0096-y. eCollection 2018.
3 Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem. 2002 Dec 20;277(51):49598-604. doi: 10.1074/jbc.M209100200. Epub 2002 Oct 21.
4 Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer.J Dent Res. 2015 Apr;94(4):584-93. doi: 10.1177/0022034515570156. Epub 2015 Feb 9.
5 MMP13 Contributes to Dental Caries Associated with Developmental Defects of Enamel.Caries Res. 2019;53(4):441-446. doi: 10.1159/000496372. Epub 2019 Feb 13.
6 Developmental biology and genetics of dental malformations.Orthod Craniofac Res. 2007 May;10(2):45-52. doi: 10.1111/j.1601-6343.2007.00384.x.
7 Thyrotropin receptor antibodies and a genetic hint in antithyroid drug-induced adverse drug reactions.Expert Opin Drug Saf. 2018 Aug;17(8):775-784. doi: 10.1080/14740338.2018.1502747. Epub 2018 Aug 1.
8 Expression Pattern of Matrix Metalloproteinase 20 (MMP20) in Human Tumors.Anticancer Res. 2016 Jun;36(6):2713-8.
9 Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.Cancer Med. 2019 May;8(5):2167-2178. doi: 10.1002/cam4.2117. Epub 2019 Apr 1.
10 MMP20 and ARMS2/HTRA1 Are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration.Ophthalmology. 2015 Nov;122(11):2295-2302.e2. doi: 10.1016/j.ophtha.2015.07.032. Epub 2015 Sep 1.
11 Prognostic significance of matrix metalloproteinase-20 overexpression in laryngeal squamous cell carcinoma.Acta Otolaryngol. 2011 Jul;131(7):769-73. doi: 10.3109/00016489.2011.560186. Epub 2011 Apr 5.
12 Common variants in MMP20 at 11q22.2 predispose to 11q deletion and neuroblastoma risk.Nat Commun. 2017 Sep 18;8(1):569. doi: 10.1038/s41467-017-00408-8.
13 MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet. 2005 Mar;42(3):271-5. doi: 10.1136/jmg.2004.024505.
14 Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.Front Physiol. 2017 Jun 14;8:398. doi: 10.3389/fphys.2017.00398. eCollection 2017.
15 Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis.Ann Rheum Dis. 1999 Nov;58(11):691-7. doi: 10.1136/ard.58.11.691.
16 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
17 Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.