Collagenase 3
Details
- Name
- Collagenase 3
- Kind
- protein
- Synonyms
- 3.4.24.-
- Matrix metalloproteinase-13
- MMP-13
- Gene Name
- MMP13
- UniProtKB Entry
- P45452Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0010677|Collagenase 3 MHPGVLAAFLFLSWTHCRALPLPSGGDEDDLSEEDLQFAERYLRSYYHPTNLAGILKENA ASSMTERLREMQSFFGLEVTGKLDDNTLDVMKKPRCGVPDVGEYNVFPRTLKWSKMNLTY RIVNYTPDMTHSEVEKAFKKAFKVWSDVTPLNFTRLHDGIADIMISFGIKEHGDFYPFDG PSGLLAHAFPPGPNYGGDAHFDDDETWTSSSKGYNLFLVAAHEFGHSLGLDHSKDPGALM FPIYTYTGKSHFMLPDDDVQGIQSLYGPGDEDPNPKHPKTPDKCDPSLSLDAITSLRGET MIFKDRFFWRLHPQQVDAELFLTKSFWPELPNRIDAAYEHPSHDLIFIFRGRKFWALNGY DILEGYPKKISELGLPKEVKKISAAVHFEDTGKTLLFSGNQVWRYDDTNHIMDKDYPRLI EEDFPGIGDKVDAVYEKNGYIYFFNGPIQFEYSIWSNRIVRVMPANSILWC
- Number of residues
- 471
- Molecular Weight
- 53819.32
- Theoretical pI
- 5.31
- GO Classification
- Functionscalcium ion binding / collagen binding / metalloendopeptidase activity / zinc ion bindingProcessesbone mineralization / bone morphogenesis / collagen catabolic process / endochondral ossification / extracellular matrix disassembly / extracellular matrix organization / growth plate cartilage development / proteolysisComponentsextracellular region / extracellular space
- General Function
- Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion
- Specific Function
- calcium ion binding
- Pfam Domain Function
- Signal Regions
- 1-19
- Transmembrane Regions
- Not Available
- Cellular Location
- Secreted, extracellular space, extracellular matrix
- Gene sequence
>lcl|BSEQ0010678|Collagenase 3 (MMP13) ATGCATCCAGGGGTCCTGGCTGCCTTCCTCTTCTTGAGCTGGACTCATTGTCGGGCCCTG CCCCTTCCCAGTGGTGGTGATGAAGATGATTTGTCTGAGGAAGACCTCCAGTTTGCAGAG CGCTACCTGAGATCATACTACCATCCTACAAATCTCGCGGGAATCCTGAAGGAGAATGCA GCAAGCTCCATGACTGAGAGGCTCCGAGAAATGCAGTCTTTCTTCGGCTTAGAGGTGACT GGCAAACTTGACGATAACACCTTAGATGTCATGAAAAAGCCAAGATGCGGGGTTCCTGAT GTGGGTGAATACAATGTTTTCCCTCGAACTCTTAAATGGTCCAAAATGAATTTAACCTAC AGAATTGTGAATTACACCCCTGATATGACTCATTCTGAAGTCGAAAAGGCATTCAAAAAA GCCTTCAAAGTTTGGTCCGATGTAACTCCTCTGAATTTTACCAGACTTCACGATGGCATT GCTGACATCATGATCTCTTTTGGAATTAAGGAGCATGGCGACTTCTACCCATTTGATGGG CCCTCTGGCCTGCTGGCTCATGCTTTTCCTCCTGGGCCAAATTATGGAGGAGATGCCCAT TTTGATGATGATGAAACCTGGACAAGTAGTTCCAAAGGCTACAACTTGTTTCTTGTTGCT GCGCATGAGTTCGGCCACTCCTTAGGTCTTGACCACTCCAAGGACCCTGGAGCACTCATG TTTCCTATCTACACCTACACCGGCAAAAGCCACTTTATGCTTCCTGATGACGATGTACAA GGGATCCAGTCTCTCTATGGTCCAGGAGATGAAGACCCCAACCCTAAACATCCAAAAACG CCAGACAAATGTGACCCTTCCTTATCCCTTGATGCCATTACCAGTCTCCGAGGAGAAACA ATGATCTTTAAAGACAGATTCTTCTGGCGCCTGCATCCTCAGCAGGTTGATGCGGAGCTG TTTTTAACGAAATCATTTTGGCCAGAACTTCCCAACCGTATTGATGCTGCATATGAGCAC CCTTCTCATGACCTCATCTTCATCTTCAGAGGTAGAAAATTTTGGGCTCTTAATGGTTAT GACATTCTGGAAGGTTATCCCAAAAAAATATCTGAACTGGGTCTTCCAAAAGAAGTTAAG AAGATAAGTGCAGCTGTTCACTTTGAGGATACAGGCAAGACTCTCCTGTTCTCAGGAAAC CAGGTCTGGAGATATGATGATACTAACCATATTATGGATAAAGACTATCCGAGACTAATA GAAGAAGACTTCCCAGGAATTGGTGATAAAGTAGATGCTGTCTATGAGAAAAATGGTTAT ATCTATTTTTTCAACGGACCCATACAGTTTGAATACAGCATCTGGAGTAACCGTATTGTT CGCGTCATGCCAGCAAATTCCATTTTGTGGTGTTAA
- Chromosome Location
- 11
- Locus
- 11q22.2
- External Identifiers
Resource Link UniProtKB ID P45452 UniProtKB Entry Name MMP13_HUMAN GenBank Protein ID 516386 GenBank Gene ID X75308 GeneCard ID MMP13 GenAtlas ID MMP13 HGNC ID HGNC:7159 PDB ID(s) 1EUB, 1FLS, 1FM1, 1PEX, 1XUC, 1XUD, 1XUR, 1YOU, 1ZTQ, 2D1N, 2E2D, 2OW9, 2OZR, 2PJT, 2YIG, 3ELM, 3I7G, 3I7I, 3KEC, 3KEJ, 3KEK, 3KRY, 3LJZ, 3O2X, 3TVC, 3WV1, 3WV2, 3WV3, 3ZXH, 456C, 4A7B, 4FU4, 4FVL, 4G0D, 4JP4, 4JPA, 4L19, 5B5O, 5B5P, 5BOT, 5BOY, 5BPA, 5UWK, 5UWL, 5UWM, 5UWN, 7JU8, 830C KEGG ID hsa:4322 IUPHAR/Guide To Pharmacology ID 1637 NCBI Gene ID 4322 - General References
- Freije JM, Diez-Itza I, Balbin M, Sanchez LM, Blasco R, Tolivia J, Lopez-Otin C: Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem. 1994 Jun 17;269(24):16766-73. [Article]
- Willmroth F, Peter HH, Conca W: A matrix metalloproteinase gene expressed in human T lymphocytes is identical with collagenase 3 from breast carcinomas. Immunobiology. 1998 Feb;198(4):375-84. [Article]
- 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. [Article]
- 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. [Article]
- Knauper V, Lopez-Otin C, Smith B, Knight G, Murphy G: Biochemical characterization of human collagenase-3. J Biol Chem. 1996 Jan 19;271(3):1544-50. [Article]
- Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G: Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996 Jul 19;271(29):17124-31. [Article]
- Fosang AJ, Last K, Knauper V, Murphy G, Neame PJ: Degradation of cartilage aggrecan by collagenase-3 (MMP-13). FEBS Lett. 1996 Feb 12;380(1-2):17-20. [Article]
- Borden P, Solymar D, Sucharczuk A, Lindman B, Cannon P, Heller RA: Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes. J Biol Chem. 1996 Sep 20;271(38):23577-81. [Article]
- Johansson N, Saarialho-Kere U, Airola K, Herva R, Nissinen L, Westermarck J, Vuorio E, Heino J, Kahari VM: Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development. Dev Dyn. 1997 Mar;208(3):387-97. [Article]
- Knauper V, Cowell S, Smith B, Lopez-Otin C, O'Shea M, Morris H, Zardi L, Murphy G: The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction. J Biol Chem. 1997 Mar 21;272(12):7608-16. [Article]
- Bonafe L, Liang J, Gorna MW, Zhang Q, Ha-Vinh R, Campos-Xavier AB, Unger S, Beckmann JS, Le Bechec A, Stevenson B, Giedion A, Liu X, Superti-Furga G, Wang W, Spahr A, Superti-Furga A: MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type. Am J Med Genet A. 2014 May;164A(5):1175-9. doi: 10.1002/ajmg.a.36431. Epub 2014 Mar 19. [Article]
- 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. [Article]
- Li D, Weber DR, Deardorff MA, Hakonarson H, Levine MA: Exome sequencing reveals a nonsense mutation in MMP13 as a new cause of autosomal recessive metaphyseal anadysplasia. Eur J Hum Genet. 2015 Feb;23(2):264-6. doi: 10.1038/ejhg.2014.76. Epub 2014 Apr 30. [Article]
- Gomis-Ruth FX, Gohlke U, Betz M, Knauper V, Murphy G, Lopez-Otin C, Bode W: The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain. J Mol Biol. 1996 Dec 6;264(3):556-66. [Article]
- Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF: Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat Struct Biol. 1999 Mar;6(3):217-21. [Article]
- Zhang X, Gonnella NC, Koehn J, Pathak N, Ganu V, Melton R, Parker D, Hu SI, Nam KY: Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1. J Mol Biol. 2000 Aug 11;301(2):513-24. [Article]
- Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R: High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor. J Mol Biol. 2000 Sep 22;302(3):671-89. [Article]
- Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA: Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14. Bioorg Med Chem Lett. 2005 Apr 1;15(7):1807-10. [Article]
- Engel CK, Pirard B, Schimanski S, Kirsch R, Habermann J, Klingler O, Schlotte V, Weithmann KU, Wendt KU: Structural basis for the highly selective inhibition of MMP-13. Chem Biol. 2005 Feb;12(2):181-9. [Article]
- Johnson AR, Pavlovsky AG, Ortwine DF, Prior F, Man CF, Bornemeier DA, Banotai CA, Mueller WT, McConnell P, Yan C, Baragi V, Lesch C, Roark WH, Wilson M, Datta K, Guzman R, Han HK, Dyer RD: Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J Biol Chem. 2007 Sep 21;282(38):27781-91. Epub 2007 Jul 10. [Article]
- Maskos K, Lang R, Tschesche H, Bode W: Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2. J Mol Biol. 2007 Mar 2;366(4):1222-31. Epub 2006 Dec 1. [Article]
- Monovich LG, Tommasi RA, Fujimoto RA, Blancuzzi V, Clark K, Cornell WD, Doti R, Doughty J, Fang J, Farley D, Fitt J, Ganu V, Goldberg R, Goldstein R, Lavoie S, Kulathila R, Macchia W, Parker DT, Melton R, O'Byrne E, Pastor G, Pellas T, Quadros E, Reel N, Roland DM, Sakane Y, Singh H, Skiles J, Somers J, Toscano K, Wigg A, Zhou S, Zhu L, Shieh WC, Xue S, McQuire LW: Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13. J Med Chem. 2009 Jun 11;52(11):3523-38. doi: 10.1021/jm801394m. [Article]
- Schnute ME, O'Brien PM, Nahra J, Morris M, Howard Roark W, Hanau CE, Ruminski PG, Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Patt WC, Shieh HS, Collins B, Pavlovsky AG, Palmquist KE, Aston KW, Hitchcock J, Rogers MD, McDonald J, Johnson AR, Munie GE, Wittwer AJ, Man CF, Settle SL, Nemirovskiy O, Vickery LE, Agawal A, Dyer RD, Sunyer T: Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. doi: 10.1016/j.bmcl.2009.11.081. Epub 2009 Nov 22. [Article]
- Becker DP, Barta TE, Bedell LJ, Boehm TL, Bond BR, Carroll J, Carron CP, Decrescenzo GA, Easton AM, Freskos JN, Funckes-Shippy CL, Heron M, Hockerman S, Howard CP, Kiefer JR, Li MH, Mathis KJ, McDonald JJ, Mehta PP, Munie GE, Sunyer T, Swearingen CA, Villamil CI, Welsch D, Williams JM, Yu Y, Yao J: Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease. J Med Chem. 2010 Sep 23;53(18):6653-80. doi: 10.1021/jm100669j. [Article]
- Devel L, Beau F, Amoura M, Vera L, Cassar-Lajeunesse E, Garcia S, Czarny B, Stura EA, Dive V: Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins. J Biol Chem. 2012 Aug 3;287(32):26647-56. doi: 10.1074/jbc.M112.380782. Epub 2012 Jun 11. [Article]
- De Savi C, Waterson D, Pape A, Lamont S, Hadley E, Mills M, Page KM, Bowyer J, Maciewicz RA: Hydantoin based inhibitors of MMP13--discovery of AZD6605. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4705-12. doi: 10.1016/j.bmcl.2013.05.089. Epub 2013 Jun 10. [Article]
- Stura EA, Visse R, Cuniasse P, Dive V, Nagase H: Crystal structure of full-length human collagenase 3 (MMP-13) with peptides in the active site defines exosites in the catalytic domain. FASEB J. 2013 Nov;27(11):4395-405. doi: 10.1096/fj.13-233601. Epub 2013 Aug 2. [Article]
- Kennedy AM, Inada M, Krane SM, Christie PT, Harding B, Lopez-Otin C, Sanchez LM, Pannett AA, Dearlove A, Hartley C, Byrne MH, Reed AA, Nesbit MA, Whyte MP, Thakker RV: MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). J Clin Invest. 2005 Oct;115(10):2832-42. [Article]
- Lausch E, Keppler R, Hilbert K, Cormier-Daire V, Nikkel S, Nishimura G, Unger S, Spranger J, Superti-Furga A, Zabel B: Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am J Hum Genet. 2009 Aug;85(2):168-78. doi: 10.1016/j.ajhg.2009.06.014. Epub 2009 Jul 16. [Article]
Associated Data
- Drug Relations