Mammalian MMPs and Substrates

Mammalian MMPs and Substrates

Protease	MMP Number	EC Number	Chromosome location (human)	Matrix substrates	Bioactive substrates	Bioactivity	Reference
Collagenases
Collagenase (-1) (tissue collagenase interstitial collagenase)	MMP-1	3.4.24.7	11q22-q23	Native collagen types: III>I>II, VII, X Gelatin Aggrecan Link protein Entactin Tenascin Perlecan	MCP-1 MCP-3 MCP-4 Stromal cell-derived factor (SDF) Pro-1L-1b 1L-1-b IGF-BP-2 IGF-BP-3 Perlecan Pro-TNF-a Pro-MMP-1 Pro-MMP-2 a1-proteinase inhibitor a1-antichymotrypsin a2-macroglobulin	Partial loss of agonist Agonist to antagonist Agonist to antagonist Inactivation Activation Degradation Active IGF release Active IGF release Active FGF release Soluble active TNF-a MMP-1 activation MMP-2 activation Inactivation Inactivation	McQuibban et al 2002 McQuibban et al 2000 McQuibban et al 2002 McQuibban et al 2001 Hazuda et al 1990 Itoh et al 1996 Rajah et al 1996 Fowlkes et al 1994 Whitelock et al 1996 Gearing et al 1994
Collagenase-2 (neutrophil collagenase)	MMP-8	3.4.24.34	11q21-q22	Native collagen types: I>II>III, VII, X Gelatin Entactin Aggrecan Tenascin	MCP-1 Pro-TNF-a L-selection IGF-BP Pro-MMP-8 a1-proteinase inhibitor a2-macroglobulin	Partial loss of agonist Soluble active TNF-a Release Active IGF release MMP-8 Inactivation	McQuibban et al 2002
Collagenase-3	MMP-13		11q22.3	Native collagen types: II>III>I, VII, X Gelatin Entactin Tenascin Aggrecan	MCP-3 SDF Pro-TNF-a Pro-MMP-9 Pro-MMP-13 a1-antichymotrypsin a2-macroglobulin	Agonist to antagonist Inactivation Soluble active TNF-a MMP-9 activation MMP-13 activation Inactivation	McQuibban et al 2002 McQuibban et al 2001 Overall et al 2002
Collagenase-4, xCol4 (Xenopus) (no known human homologue)	MMP-18			Native collagen type I, II, III Gelatin			Stolow et al 1996
Gelatinases
Gelatinase A (72-kDa gelatinase, 72-kDa type IV collagenase)	MMP-2	3.4.24.24	16q13	Denatured collagens (gelatin) Native collagen types: I, IV, V, VII, X, XI Elastin Fibronectin Laminin-5 Aggrecan Brevican Neurocan BM-40 Decorin Vitronectin	SDF MCP-3 Pro-TGF-b1 Pro-TNF-a Pro-IL-1b IGFBP-3 IGFBP-5 FGFR-1 Big endothelin-1 Pregnancy zone protein Substance P Decorin IGFBP Galectin-3 Pro-MMP-1 Pro-MMP-2 Pro-MMP-13 a1-proteinase inhibitor a2-macroglobulin	Inactive SDF Agonist to antagonist Active TGF-b1 Soluble active TNF-a Active IL-1b Bioavailable IGF Bioavailable IGF FGFR-1 ectodomain -> vasoconstrictor Active TGF-b release Active IGF release Degraded (loss of macrophage chemoattraction?) MMP-1 MMP-2 MMP-13 Inactivation	McQuibban et al 2001 McQuibban et al 2000 Yu & Stamenkovic 2000 Gearing et al 1994 Schonbeck et al 1998 Fowlkes et al 1996 Thrailkill et al 1995 Levi et al 1996 Fernandez-Patro etal 1999 Imai et al 1997 Ochieng et al 1994
Gelatinase B (92-kDa gelatinase)	MMP-9	3.4.24.35	20q11.2-q13.1	Denatured collagens (gelatin) Native collagen types: I, IV, V, VII, X, XI Elastin Fibronectin Laminin Aggrecan Link protein Vitronectin	SDF Pro-IL-8 CTAP-III/NAP-2 GROa PF-4 Pro-TNF-a Pro-TGF-b1 Pro-IL-1b Cell-surface IL-2Ra FGF-R1 Plasminogen Galectin-3 ? Pro-MMP-2 Pro-MMP-9 Pro-MMP-13 a1-proteinase inhibitor a2-macroglobulin	Inactivation Active IL-8 Degraded Degraded Degraded Soluble active TNF-a Active TGF-b1 Active IL-1b Release of IL-2Ra Shedding Angiostatin Degraded Bioavailable VEGF MMP-2 MMP-9 MMP-13 Inactivation	McQuibban et al 2001 Van den Steen 2000 Van den Steen 2000 Van den Steen 2000 Van den Steen 2000 Liu et al 2000 Yu & Stamenkovic 2000 Schonbeck et al 1998 Sheu et al 2001 Patterson & Sang 1997,Bergers et al 2000 Ochieng et al 1994 Pozzi et al 2000
Membrane-anchored MMPs
MT1-MMP	MMP-14		14q11-q12	Native collagen types: I, II, III Gelatin Fibronectin Vitronectin Aggrecan	MCP-3 SDF Cell-surface CD44 Cell-surface tissue transglutaminase (tTG) Pro-TNF-a Pro-MMP-2 Pro-MMP-13 a1-proteinase inhibitor a2-macroglobulin	Agonist to antagonist Inactivation CD44 release tTG release Soluble active TNF-a MMP-2 MMP-13 Inactivation	McQuibban et al 2002 McQuibban et al 2001 Kajita et al 2001 Belkin et al 2001 d’Ortho et al 1997
MT2-MMP	MMP-15		16q13-q21	Proteoglycan	Pro-MMP-2 Cell-surface bound tTG Pro-TNF-a	MMP-2 tTG release Soluble active TNF-a	Morrison et al 2001 Belkin et al 2001 d’Ortho et al 1997
MT3-MMP	MMP-16		8q21	Native type III collagen Fibronectin	Pro-MMP-2 Cell-surface bound tTG Pro-TNF-a	MMP-2 Release of tTG Soluble active TNF-a	Belkin et al 2001 d’Ortho et al 1997
MT4-MMP	MMP-17		12q24.3	Gelatin Fibrin/fibrinogen	Pro-MMP-2 Pro-TNF-a	MMP-2 Soluble active TNF-a	Wang et al 1999 English et al 2000, Wang et al 1999
MT5-MMP	MMP-24		20q11.2	Fibronectin Proteoglycans Gelatin	Pro-MMP-2	MMP-2	Llano et al 1999, Pei 1999a, Wang et al 1999
MT6-MMP, Leukolysin	MMP-25		16p13.3	Native type IV collagen Gelatin Fibronectin Proteoglycans (DSPG, CSPG) Laminin-1 Fibrin/fibrinogen	Pro-MMP-2 Pro-MMP-9 a1-proteinase inhibitor	MMP-2 MMP-9 Inactivation	Velasco et al 2000, English et al 2001
Stromelysins
Stromelysin-1 (Proteoglycanase)	MMP-3	3.4.24.17	11q23	Aggrecan Laminin Fibronectin Non triple helical regions of native collagen types: II, III, IV, V, IX, X, XI Gelatin Entactin Perlecan Decorin Tenascin Vitronectin Fibrin/fibrinogen Link protein Elastin	MCP-1 MCP-2 MCP-3 MCP-4 SDF Pro-TNF-a L-selection Pro-HB-EGF Pro-IL-1b Perlecan Decorin Plasminogen E-cadherin IGFBP-3 Pro-MMP-1 Pro-MMP-3 Pro-MMP-7 Pro-MMP-8 Pro-MMP-9 Pro-MMP-13 a1-proteinase inhibitor a1-antichymotrypsin a2-macroglobulin	Partial inactivation Agonist to antagonist Agonist to antagonist Agonist to antagonist Inactivation Soluble active TNF-a Shedding HB-EGF 1L-1b FGF release TGF-b release Angiostatin E-cadherin ectodomain Active IGF MMP-1 MMP-3 MMP-7 MMP-8 MMP-9 MMP-13 Inactivation Inactivation	McQuibban et al 2002 McQuibban et al 2002 McQuibban et al 2002 McQuibban et al 2002 McQuibban et al 2001 Suzuki et al 1997 Lijnen et al 1998 Whitelock et al 1996 Imai et al 1997 Noe et al 2001, St Croix et al 1998
Stromelysin-2	MMP-10	3.4.24.22	11q22.3-q23	Gelatin type I, III IV, V Fibronectin Proteoglycan	Pro-MMP-1 Pro-MMP-8 Pro-MMP-10	MMP-1 MMP-8 MMP-10
Stromelysin-3	MMP-11		22q11.2	Fibronectin Laminin Aggrecan	IGFBP-1 a1-proteinase inhibitor a2-macroglobulin	Active IGF release Inactivation	Manes et al 1997
Matrilysins
Matrilysin (PUMP-1)	MMP-7	3.4.24.23	11q21-q22	Fibronectin Laminin Non helical segments of native collagen types: IV, V, IX, X, XI Gelatin Aggrecan Entactin Tenascin Vitronectin Fibrin/fibrinogen	Pro-a-definsin Cell surface bound Fas-L Pro-TNF-a E-cadherin b4 integrin Plasminogen Decorin Pro-MMP-1 Pro-MMP-2 Pro-MMP-7 Pro-MMP-9 a1-proteinase inhibitor a2-macroglobulin	a-Defensin Soluble Fas-L Soluble active TNF-a Bioactive E-cadherin ectodomain b4 integrin shedding Angiostatin Active TGF-b release MMP-1 activation MMP-2 activation MMP-7 activation MMP-9 activation Inactivation	Wilson et al 1999 Fingleton et al 2001, Powell et al 1999 Haro et al 20001 Lochter et al 1997, Noe et al 2001 Von Bredow et al 1997 Patterson & Sang 1997, Pozzi et al 2000 Imai et al 1997
Matrilysin-2, Endometase	MMP-26		11p15	Native type IV collagen Gelatin Fibronectin Fibrin/fibrinogen	IGFBP-1 Pro-MMP-9 a1-proteinase inhibitor	Active IGF release MMP-9 activation Inactivation	Park et al 2000 Uria & Lopez-Otin 2000, de Coignac et al 2000 Park et al 2000
Other MMPs
Metalloelastase (Macrophage elastase)	MMP-12	3.4.24.65	11q22.2-q22.3	Elastin Fibronectin Laminin Proteoglycan Fibrin/fibrinogen (myelin basic protein)	Plasminogen Pro-TNF-a a1-proteinase inhibitor	Angiostatin Soluble active TNF-a Inactivation	Cornelius et al 1998, Dong et al 1997 Chandler et al 1996
RASI, Stromelysin-4	MMP-19		12q14	Native type IV collagen Gelatin Laminin Fibronectin Tenascin Entactin Aggrecan COMP Fibrin/fibrinogen			Stracke et al 2000a,b
Enamelysin	MMP-20		11q22.3	Amelogenin COMP Aggrecan
XMMP (Xenopus)	MMP-21			no substrates defined
CMMP (chicken) (human homologue)	MMP-22a,b/ MMP-27		11q24	no substrates defined			Gururajan et al 1998a,b
CA-MMP	MMP-23		1p36.3	Gelatin			Pei 1999b
Epilysin	MMP-28		17q11.2	no substrates defined			Lohi et al 2001, Illman et al 2001

MMP, TIMP, MATRIX, METALLO, PROTEINASE, PROTEASE, KINETICS, ASSAYS, TISSUE INHIBITOR, PROTEOMICS, DEGRADOMICS, GELATINASE, MT-MMP, HEMOPEXIN C DOMAIN
EXOSITE, SUBSTRATE, MUTAGENESIS, PROTEIN ENGINEERING, CHEMOKINE, MASS SPECTROMETRY, ICAT, MOLECULAR BIOLOGY, CANCER, CLIP, MMP-1... MMP-2... MMP-3... MMP-7...
MMP-8... MMP-9... MMP-10... MMP-11... MMP-12Chris Overall Lab, UBC. Copyright © 2003 Canada MMP-13... MMP-14... MMP-15...MMP-16... MMP-17... MMP-18...
MMP-19... MMP-20... MMP-21... MMP-22... MMP-23... MMP-23a... MMP-23b... MMP-24... MMP-25... MMP-26... MMP-27... MMP-28... C-MMP... X-MMP... TIMP-1... TIMP-2... TIMP-3 TIMP-4

Collagenases