Matrix metalloproteinase-14

Details

Name
Matrix metalloproteinase-14
Synonyms
  • 3.4.24.80
  • Membrane-type matrix metalloproteinase 1
  • Membrane-type-1 matrix metalloproteinase
  • MMP-14
  • MMP-X1
  • MT-MMP 1
  • MT1-MMP
  • MT1MMP
  • MTMMP1
Gene Name
MMP14
Organism
Humans
Amino acid sequence
>lcl|BSEQ0012568|Matrix metalloproteinase-14
MSPAPRPPRCLLLPLLTLGTALASLGSAQSSSFSPEAWLQQYGYLPPGDLRTHTQRSPQS
LSAAIAAMQKFYGLQVTGKADADTMKAMRRPRCGVPDKFGAEIKANVRRKRYAIQGLKWQ
HNEITFCIQNYTPKVGEYATYEAIRKAFRVWESATPLRFREVPYAYIREGHEKQADIMIF
FAEGFHGDSTPFDGEGGFLAHAYFPGPNIGGDTHFDSAEPWTVRNEDLNGNDIFLVAVHE
LGHALGLEHSSDPSAIMAPFYQWMDTENFVLPDDDRRGIQQLYGGESGFPTKMPPQPRTT
SRPSVPDKPKNPTYGPNICDGNFDTVAMLRGEMFVFKERWFWRVRNNQVMDGYPMPIGQF
WRGLPASINTAYERKDGKFVFFKGDKHWVFDEASLEPGYPKHIKELGRGLPTDKIDAALF
WMPNGKTYFFRGNKYYRFNEELRAVDSEYPKNIKVWEGIPESPRGSFMGSDEVFTYFYKG
NKYWKFNNQKLKVEPGYPKSALRDWMGCPSGGRPDEGTEEETEVIIIEVDEEGGGAVSAA
AVVLPVLLLLLVLAVGLAVFFFRRHGTPRRLLYCQRSLLDKV
Number of residues
582
Molecular Weight
65893.445
Theoretical pI
7.87
GO Classification
Functions
calcium ion binding / metalloendopeptidase activity / peptidase activator activity / zinc ion binding
Processes
angiogenesis / astrocyte cell migration / branching morphogenesis of an epithelial tube / chondrocyte proliferation / collagen catabolic process / craniofacial suture morphogenesis / embryonic cranial skeleton morphogenesis / endochondral ossification / endodermal cell differentiation / endothelial cell proliferation / extracellular matrix disassembly / extracellular matrix organization / lung development / male gonad development / negative regulation of focal adhesion assembly / negative regulation of Notch signaling pathway / ovarian follicle development / positive regulation of B cell differentiation / positive regulation of cell growth / positive regulation of cell migration / positive regulation of myotube differentiation / proteolysis / response to estrogen / response to hypoxia / response to mechanical stimulus / response to oxidative stress / tissue remodeling / zymogen activation
Components
cytoplasmic vesicle / extracellular matrix / focal adhesion / Golgi lumen / integral component of plasma membrane / macropinosome / melanosome / plasma membrane
General Function
Zinc ion binding
Specific Function
Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2.
Pfam Domain Function
Transmembrane Regions
542-562
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0012569|Matrix metalloproteinase-14 (MMP14)
ATGTCTCCCGCCCCAAGACCCCCCCGTTGTCTCCTGCTCCCCCTGCTCACGCTCGGCACC
GCGCTCGCCTCCCTCGGCTCGGCCCAAAGCAGCAGCTTCAGCCCCGAAGCCTGGCTACAG
CAATATGGCTACCTGCCTCCCGGGGACCTACGTACCCACACACAGCGCTCACCCCAGTCA
CTCTCAGCGGCCATCGCTGCCATGCAGAAGTTTTACGGCTTGCAAGTAACAGGCAAAGCT
GATGCAGACACCATGAAGGCCATGAGGCGCCCCCGATGTGGTGTTCCAGACAAGTTTGGG
GCTGAGATCAAGGCCAATGTTCGAAGGAAGCGCTACGCCATCCAGGGTCTCAAATGGCAA
CATAATGAAATCACTTTCTGCATCCAGAATTACACCCCCAAGGTGGGCGAGTATGCCACA
TACGAGGCCATTCGCAAGGCGTTCCGCGTGTGGGAGAGTGCCACACCACTGCGCTTCCGC
GAGGTGCCCTATGCCTACATCCGTGAGGGCCATGAGAAGCAGGCCGACATCATGATCTTC
TTTGCCGAGGGCTTCCATGGCGACAGCACGCCCTTCGATGGTGAGGGCGGCTTCCTGGCC
CATGCCTACTTCCCAGGCCCCAACATTGGAGGAGACACCCACTTTGACTCTGCCGAGCCT
TGGACTGTCAGGAATGAGGATCTGAATGGAAATGACATCTTCCTGGTGGCTGTGCACGAG
CTGGGCCATGCCCTGGGGCTCGAGCATTCCAGTGACCCCTCGGCCATCATGGCACCCTTT
TACCAGTGGATGGACACGGAGAATTTTGTGCTGCCCGATGATGACCGCCGGGGCATCCAG
CAACTTTATGGGGGTGAGTCAGGGTTCCCCACCAAGATGCCCCCTCAACCCAGGACTACC
TCCCGGCCTTCTGTTCCTGATAAACCCAAAAACCCCACCTATGGGCCCAACATCTGTGAC
GGGAACTTTGACACCGTGGCCATGCTCCGAGGGGAGATGTTTGTCTTCAAGGAGCGCTGG
TTCTGGCGGGTGAGGAATAACCAAGTGATGGATGGATACCCAATGCCCATTGGCCAGTTC
TGGCGGGGCCTGCCTGCGTCCATCAACACTGCCTACGAGAGGAAGGATGGCAAATTCGTC
TTCTTCAAAGGAGACAAGCATTGGGTGTTTGATGAGGCGTCCCTGGAACCTGGCTACCCC
AAGCACATTAAGGAGCTGGGCCGAGGGCTGCCTACCGACAAGATTGATGCTGCTCTCTTC
TGGATGCCCAATGGAAAGACCTACTTCTTCCGTGGAAACAAGTACTACCGTTTCAACGAA
GAGCTCAGGGCAGTGGATAGCGAGTACCCCAAGAACATCAAAGTCTGGGAAGGGATCCCT
GAGTCTCCCAGAGGGTCATTCATGGGCAGCGATGAAGTCTTCACTTACTTCTACAAGGGG
AACAAATACTGGAAATTCAACAACCAGAAGCTGAAGGTAGAACCGGGCTACCCCAAGTCA
GCCCTGAGGGACTGGATGGGCTGCCCATCGGGAGGCCGGCCGGATGAGGGGACTGAGGAG
GAGACGGAGGTGATCATCATTGAGGTGGACGAGGAGGGCGGCGGGGCGGTGAGCGCGGCT
GCCGTGGTGCTGCCCGTGCTGCTGCTGCTCCTGGTGCTGGCGGTGGGCCTTGCAGTCTTC
TTCTTCAGACGCCATGGGACCCCCAGGCGACTGCTCTACTGCCAGCGTTCCCTGCTGGAC
AAGGTCTGA
Chromosome Location
14
Locus
14q11-q12
External Identifiers
ResourceLink
UniProtKB IDP50281
UniProtKB Entry NameMMP14_HUMAN
GenBank Protein ID793763
GenBank Gene IDD26512
HGNC IDHGNC:7160
General References
  1. Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M: A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994 Jul 7;370(6484):61-5. [PubMed:8015608]
  2. Takino T, Sato H, Yamamoto E, Seiki M: Cloning of a human gene potentially encoding a novel matrix metalloproteinase having a C-terminal transmembrane domain. Gene. 1995 Apr 3;155(2):293-8. [PubMed:7721107]
  3. Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P, Basset P: Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2730-4. [PubMed:7708715]
  4. Will H, Hinzmann B: cDNA sequence and mRNA tissue distribution of a novel human matrix metalloproteinase with a potential transmembrane segment. Eur J Biochem. 1995 Aug 1;231(3):602-8. [PubMed:7649159]
  5. Lohi J, Lehti K, Westermarck J, Kahari VM, Keski-Oja J: Regulation of membrane-type matrix metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate. Eur J Biochem. 1996 Jul 15;239(2):239-47. [PubMed:8706726]
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  9. Sato H, Kinoshita T, Takino T, Nakayama K, Seiki M: Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2. FEBS Lett. 1996 Sep 9;393(1):101-4. [PubMed:8804434]
  10. Noda K, Ishida S, Inoue M, Obata K, Oguchi Y, Okada Y, Ikeda E: Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2003 May;44(5):2163-70. [PubMed:12714657]
  11. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed:17081065]
  12. Bonnomet A, Polette M, Strumane K, Gilles C, Dalstein V, Kileztky C, Berx G, van Roy F, Birembaut P, Nawrocki-Raby B: The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression. Oncogene. 2008 Jun 12;27(26):3692-9. doi: 10.1038/sj.onc.1211035. Epub 2008 Jan 28. [PubMed:18223680]
  13. Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY: The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem. 2010 Nov 12;285(46):35740-9. doi: 10.1074/jbc.M110.165159. Epub 2010 Sep 13. [PubMed:20837484]
  14. Jin G, Zhang F, Chan KM, Xavier Wong HL, Liu B, Cheah KS, Liu X, Mauch C, Liu D, Zhou Z: MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development. EMBO J. 2011 Jun 1;30(11):2281-93. doi: 10.1038/emboj.2011.136. Epub 2011 May 13. [PubMed:21572390]
  15. Gu G, Zhao D, Yin Z, Liu P: BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433. [PubMed:22065321]
  16. Bordoli MR, Yum J, Breitkopf SB, Thon JN, Italiano JE Jr, Xiao J, Worby C, Wong SK, Lin G, Edenius M, Keller TL, Asara JM, Dixon JE, Yeo CY, Whitman M: A secreted tyrosine kinase acts in the extracellular environment. Cell. 2014 Aug 28;158(5):1033-44. doi: 10.1016/j.cell.2014.06.048. [PubMed:25171405]
  17. Fernandez-Catalan C, Bode W, Huber R, Turk D, Calvete JJ, Lichte A, Tschesche H, Maskos K: Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor. EMBO J. 1998 Sep 1;17(17):5238-48. [PubMed:9724659]
  18. Evans BR, Mosig RA, Lobl M, Martignetti CR, Camacho C, Grum-Tokars V, Glucksman MJ, Martignetti JA: Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. Am J Hum Genet. 2012 Sep 7;91(3):572-6. doi: 10.1016/j.ajhg.2012.07.022. Epub 2012 Aug 23. [PubMed:22922033]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00786MarimastatinvestigationalyesinhibitorDetails