Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TMIQ6)

• DOT Name: Matrix metalloproteinase-17 (MMP17)
• Synonyms: MMP-17; EC 3.4.24.-; Membrane-type matrix metalloproteinase 4; MT-MMP 4; MTMMP4; Membrane-type-4 matrix metalloproteinase; MT4-MMP; MT4MMP
• Gene Name: MMP17
• UniProt ID: MMP17_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF00045 ; PF00413 ; PF01471
• Sequence:
  MRRRAARGPGPPPPGPGLSRLPLPLLLLLALGTRGGCAAPAPAPRAEDLSLGVEWLSRFG
  YLPPADPTTGQLQTQEELSKAITAMQQFGGLEATGILDEATLALMKTPRCSLPDLPVLTQ
  ARRRRQAPAPTKWNKRNLSWRVRTFPRDSPLGHDTVRALMYYALKVWSDIAPLNFHEVAG
  SAADIQIDFSKADHNDGYPFDGPGGTVAHAFFPGHHHTAGDTHFDDDEAWTFRSSDAHGM
  DLFAVAVHEFGHAIGLSHVAAAHSIMRPYYQGPVGDPLRYGLPYEDKVRVWQLYGVRESV
  SPTAQPEEPPLLPEPPDNRSSAPPRKDVPHRCSTHFDAVAQIRGEAFFFKGKYFWRLTRD
  RHLVSLQPAQMHRFWRGLPLHLDSVDAVYERTSDHKIVFFKGDRYWVFKDNNVEEGYPRP
  VSDFSLPPGGIDAAFSWAHNDRTYFFKDQLYWRYDDHTRHMDPGYPAQSPLWRGVPSTLD
  DAMRWSDGASYFFRGQEYWKVLDGELEVAPGYPQSTARDWLVCGDSQADGSVAAGVDAAE
  GPRAPPGQHDQSRSEDGYEVCSCTSGASSPPGAPGPLVAATMLLLLPPLSPGALWTAAQA
  LTL
• Function: Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Cleaves pro-TNF-alpha at the '74-Ala-|-Gln-75' site. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin.
• Tissue Specificity: Expressed in brain, leukocytes, colon, ovary testis and breast cancer. Expressed also in many transformed and non-transformed cell types.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway: Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Matrix metalloproteinase-17 (MMP17).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Matrix metalloproteinase-17 (MMP17).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Matrix metalloproteinase-17 (MMP17).	[6]

6 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-17 (MMP17).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Matrix metalloproteinase-17 (MMP17).	[3]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Matrix metalloproteinase-17 (MMP17).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Matrix metalloproteinase-17 (MMP17).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Matrix metalloproteinase-17 (MMP17).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Matrix metalloproteinase-17 (MMP17).	[3]

References

• [1] 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.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] 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.
• [5] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [6] 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.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.