Matrix metalloproteinase-14

NameMatrix 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 NameMMP14
OrganismHuman
Amino acid sequence
>lcl|BSEQ0012568|Matrix metalloproteinase-14
MSPAPRPPRCLLLPLLTLGTALASLGSAQSSSFSPEAWLQQYGYLPPGDLRTHTQRSPQS
LSAAIAAMQKFYGLQVTGKADADTMKAMRRPRCGVPDKFGAEIKANVRRKRYAIQGLKWQ
HNEITFCIQNYTPKVGEYATYEAIRKAFRVWESATPLRFREVPYAYIREGHEKQADIMIF
FAEGFHGDSTPFDGEGGFLAHAYFPGPNIGGDTHFDSAEPWTVRNEDLNGNDIFLVAVHE
LGHALGLEHSSDPSAIMAPFYQWMDTENFVLPDDDRRGIQQLYGGESGFPTKMPPQPRTT
SRPSVPDKPKNPTYGPNICDGNFDTVAMLRGEMFVFKERWFWRVRNNQVMDGYPMPIGQF
WRGLPASINTAYERKDGKFVFFKGDKHWVFDEASLEPGYPKHIKELGRGLPTDKIDAALF
WMPNGKTYFFRGNKYYRFNEELRAVDSEYPKNIKVWEGIPESPRGSFMGSDEVFTYFYKG
NKYWKFNNQKLKVEPGYPKSALRDWMGCPSGGRPDEGTEEETEVIIIEVDEEGGGAVSAA
AVVLPVLLLLLVLAVGLAVFFFRRHGTPRRLLYCQRSLLDKV
Number of residues582
Molecular Weight65893.445
Theoretical pI7.87
GO Classification
Functions
  • zinc ion binding
  • calcium ion binding
  • peptidase activator activity
  • metalloendopeptidase activity
Processes
  • response to oxidative stress
  • negative regulation of Notch signaling pathway
  • male gonad development
  • tissue remodeling
  • endodermal cell differentiation
  • branching morphogenesis of an epithelial tube
  • collagen catabolic process
  • zymogen activation
  • endochondral ossification
  • negative regulation of focal adhesion assembly
  • extracellular matrix disassembly
  • ovarian follicle development
  • extracellular matrix organization
  • embryonic cranial skeleton morphogenesis
  • positive regulation of cell migration
  • astrocyte cell migration
  • lung development
  • endothelial cell proliferation
  • response to hypoxia
  • positive regulation of B cell differentiation
  • positive regulation of cell growth
  • positive regulation of myotube differentiation
  • response to estrogen
  • proteolysis
  • angiogenesis
  • chondrocyte proliferation
  • craniofacial suture morphogenesis
  • response to mechanical stimulus
Components
  • melanosome
  • cytoplasmic vesicle
  • integral component of plasma membrane
  • macropinosome
  • Golgi lumen
  • extracellular matrix
  • focal adhesion
  • plasma membrane
General FunctionZinc ion binding
Specific FunctionSeems 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 Regions542-562
GenBank Protein ID793763
UniProtKB IDP50281
UniProtKB Entry NameMMP14_HUMAN
Cellular LocationMembrane
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
GenBank Gene IDD26512
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:7160
Chromosome Location14
Locus14q11-q12
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. 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. 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. 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. 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. 8706726
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. 12508121
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22922033