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Information on EC 3.4.24.80 - membrane-type matrix metalloproteinase-1
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- 3.4.24.80
- metalloproteinases
- mmp-2
- metastasis
- collagen
- endothelial
- angiogenesis
- breast
-
zymography
- gelatin
- prommp-2
- gelatinase
-
pericellular
- bone
- timps
- integrins
-
basement
- mesenchymal
-
invasiveness
-
squamous
-
angiogenic
- matrigel
- fibrosarcoma
-
invadopodia
-
progelatinase
- ectodomain
-
gelatinolytic
- zymogen
- furin
-
anti-invasive
-
membrane-tethered
-
collagen-rich
-
membrane-anchored
-
mt-mmps
- proenzyme
- hemopexin
-
collagenolytic
- proproteins
-
emmprin
-
pro-matrix
-
convertase
- alphavbeta3
-
matrix-degrading
-
hemopexin-like
-
mmp-dependent
- cortactin
-
invasion-promoting
-
cona-induced
- sheddase
- drug development
- medicine
- reck
- diagnostics
- endoglin
The enzyme appears in viruses and cellular organisms
Reaction Schemes
endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at Asn37-/-Leu. Other bonds hydrolysed include Gly35-/-Ile in the propeptide of collagenase 3, and Asn341-/-Phe, Asp441-/-Leu and Gln354-/-Thr in the aggrecan interglobular domain
Synonyms
ectMMP-14, gelatinase A, interstitial MT1-MMP, matrix metalloprotease 14, matrix metalloproteinase 14, matrix metalloproteinase MT 1, matrix metalloproteinase MT-MMP-1, matrix metalloproteinase MT1-MMP, matrix metalloproteinase-14, membrane type 1 matrix metalloproteinase, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
matrix metalloprotease 14
-
-
-
-
matrix metalloproteinase 14
matrix metalloproteinase MT 1
-
-
-
-
matrix metalloproteinase MT-MMP-1
-
-
-
-
matrix metalloproteinase MT1-MMP
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-
-
-
membrane type 1 matrix metalloproteinase
membrane type 1 MMP
membrane type 1-matrix metalloproteinase
membrane type matrix metalloproteinase
membrane type MMP-1
membrane type-1 matrix metalloprotease 1
-
-
-
-
membrane type-1 matrix metalloproteinase
membrane type-I matrix metalloproteinase
membrane type-I MMP
membrane-type 1 matrix metalloproteinase
membrane-type matrix metalloproteinase MT1-MMP
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-
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-
membrane-type matrix metalloproteinase-1
membrane-type metalloproteinase MT1-MMP
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-
-
-
MMP-14
MMP14
MT-MMP-1
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-
-
-
MT-MMP1
MT1-MMP
proteinase, matrix metallo-
-
-
-
-
matrix metalloproteinase 14
-
-
-
-
membrane type 1 matrix metalloproteinase
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-
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membrane type 1 matrix metalloproteinase
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-
membrane type 1 matrix metalloproteinase
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membrane type 1-matrix metalloproteinase
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-
membrane-type 1 matrix metalloproteinase
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-
MMP-14
-
-
-
-
MMP-14
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MT-MMP1
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-
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MT1-MMP
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-
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MT1-MMP
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-
MT1-MMP
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at Asn37-/-Leu. Other bonds hydrolysed include Gly35-/-Ile in the propeptide of collagenase 3, and Asn341-/-Phe, Asp441-/-Leu and Gln354-/-Thr in the aggrecan interglobular domain
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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
-
-
-
-
hydrolysis
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
161384-17-4
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7-methoxycoumarin-4-yl)-acetyl-L-Lys-Pro-Leu-Gly-Leu-Lys(N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)-Ala-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)-acetyl-Pro-Leu-Ala-Cys(p-OmeBz)-Trp-Ala-Arg(Dpa)-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)-acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)-Ala-Arg-NH2 + H2O
(7-methoxycoumarin-4-yl)-acetyl-Pro-Leu-Gly + Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)-Ala-Arg-NH2
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Tyr-Ala-Nva-Trp-Met-Lys-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-GTQGQEARGS-dinitrophenol NH2 + H2O
?
-
substrate covering the aggrecanase cleavage site of aggrecan
-
-
?
(7-methoxycoumarin-4-yl)acetyl-L-Pro-Leu-Gly-Leu-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-Ala-Arg-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-LAQAVRSSK-dinitrophenol NH2 + H2O
?
-
quenched fluorescent substrate mimicking the cleavage site of pro tumor necrosis factor alpha
-
-
?
(7-methoxycoumarin-4-yl)acetyl-P-3-cyclohexylalanyl-norvalyl-HA-dinitrophenol NH2 + H2O
?
-
collagenase substrate
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-(N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)-NH2 + H2O
?
-
degradation of synthetic substrate is pH-independent
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Ala-Cys(p-OMeBz)-Trp-Ala-Arg(N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Ala-Gln-Ala-Val-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Arg-Ser-Ser-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Ala-Nva-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Lys-Pro-Leu-Ala-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
-
-
-
-
?
alpha subunit of low density lipoprotein receptor-related protein + H2O
?
-
-
-
-
?
brain-specific angiogenesis inhibitor 1 + H2O
vasculostatin-120 + vasculostatin-40
-
the N terminus of BAI1 is cleaved extracellularly to generate a truncated receptor (vasculostatin-120) and a 40000 Da fragment (vasculostatin-40)
-
-
?
collagen I alpha-1 chain + H2O
?
-
overall enzymatic activity is higher on the alpha-2 chain for both MMP-1 and MMP-2. In MMP-2 a marked difference for substrate affinity (higher for the alpha-1 chain) is overwhelmed by an even more marked propensity to cleave the alpha-2 chain
-
-
?
collagen I alpha-2 chain + H2O
?
-
overall enzymatic activity is higher on the alpha-2 chain for both MMP-1 and MMP-2. In MMP-2 a marked difference for substrate affinity (higher for the alpha-1 chain) is overwhelmed by an even more marked propensity to cleave the alpha-2 chain
-
-
?
collagen type I alpha-1 chain + H2O
?
-
the MMP-14 ectodomain preferentially cleaves the alpha-1 chain of collagen type I
-
-
?
cross-linked fibrin II + H2O
?
-
des-fibrinopeptides A and B, prepared by clotting fibrinogen with thrombin in the presence of factor XIIIa
-
-
?
endoglin + H2O
soluble endoglin + ?
-
MMP-14 cleaves membrane-bound endoglin at a site in close proximity to the transmembrane domain between Gly586-Leu-587
-
-
?
epidermal growth factor receptor + H2O
?
-
the enzyme plays a role in transactivation
-
-
?
extracellular matrix metalloproteinase inducer + H2O
extracellular matrix metalloproteinase inducer fragment + ?
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-
22000 Da in length
-
?
galectin-3
?
-
cleaved to the 22 kDa degradation product when exposed to cells expressing membrane-anhored wild type MT1-MMP or the recombinant 50 kDa enzyme form
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-
?
heparin-binding epidermal growth factor + H2O
heparin-binding epidermal growth factor mN3-fragment + ?
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-
-
-
?
inactive pro-matrix metalloproteinase-2 + H2O
active matrix metalloproteinase-2 + ?
-
-
-
-
?
kidney injury molecule-1 + H2O
?
-
the enzyme cleaves and sheds the substrate's ectodomain
-
-
?
N-hexanoyl((GP-4-hydroxy-L-proline)5GPK(7-methoxycoumarin-4-yl)acetyl)GPQGLRGQK(2,4-dinitrophenyl)GVR((GP-4-hydroxy-L-proline)5-NH2 + H2O
N-hexanoyl((GP-4-hydroxy-L-proline)5GPK(7-methoxycoumarin-4-yl)acetyl)GPQGL + RGQK(2,4-dinitrophenyl)GVR((GP-4-hydroxy-L-proline)5-NH2
-
-
-
-
?
neuronal glial antigen 2 + H2O
?
three (210, 160, and 51-52 kDa) major cleavage products are formed
-
-
?
PA83
?
-
efficiently cleaved by MT1-MMP at the substrate-enzyme ratio as low as 1: 50
-
-
?
pro-MMP-2
?
-
MT1-MMP accomplishes full pro-MMP-2 activation, cleavage within the prodomain at the Asn37-Leu38 peptide bond
-
-
?
progelatinase A + H2O
gelatinase A + ?
-
activation, gelatinase A is matrix metalloproteinase-2
-
-
?
progelatinase A E375A + H2O
?
-
syn: pro-matrix metalloproteinase 2, cleaves at N37-L38 only
-
-
?
rat-tail tendon type I collagen + H2O
?
-
degraded by deltaTM-MT1-MMP at 37°C
-
-
?
receptor of complement component 1q + H2O
?
-
cleaves at Gly79-Gln80, cleavage with CAT/PEX domain leads to fragments with the following MW: 17 kDa, 12 kDa and 11 kDa
-
-
?
syndecan-1 G245L glutathione transferase protein + H2O
?
-
cleaves at G82-L83 peptide bond
-
-
?
type I collagen + H2O
denatured type I collagen
-
bound by recombinant linker/hemopexin C domain of MT1-MMP
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
-
fluorescent peptide
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
?
-
cdMT1-MMP is catalytically more efficient towards small peptide substrates than deltaTM-MT1-MMP and the haemopexin domain of MT1-MMP facilitates the hydrolysis of triple-helical substrates
-
-
?
aggrecan + H2O
?
-
recombinant fusion protein with G332A mutation, substrate is cleaved at the aggrecanase site in its interglobular domain sequence segment, products are fragments with the following MW: 72 kDa, 66 kDA and 42 kDa
-
-
?
apolipoprotein E + H2O
?
-
the 34 kDa apoE protein is initially processed by MMP-14 into fragments with molecular masses of 28, 23, 21, and 11 kDa. The primary MMP-14 cleavage sites are Ala176-Ile177, Pro183-Leu184, Pro202-Leu203, and Gln249-Ile250. The MMP-14-mediated cleavage of apoE is consistent regardless of whether apoE exists in its lipid-bound or lipid-free form. Upon digestion with MMP-14, apoE loses its ability to suppress the platelet-derived growth factor-induced migration of rat vascular smooth muscle cells
-
-
?
E-cadherin + H2O
?
-
MT1-MMP sheds E-cadherin at cell-cell adherens junctions
-
-
?
Fibronectin + H2O
?
-
cell surface active pMMP-2 cDNAs bound to MT1-MMP enhances substrate digestion, cytoplasmic tail of MT1-MMP not required for digestion
-
-
?
Gelatin + H2O
?
-
-
-
-
?
Gelatin + H2O
?
-
rat-tail tendon type I collagen boiled for 5 min and denatured to gelatin, when degraded by deltaTM-MT1-MMP and cdMT1-MMP
-
-
?
heparin-binding epidermal growth factor + H2O
?
-
the enzyme removes the NH2-terminal 20 amino acids by cleaving between A-83LC
-
-
?
heparin-binding epidermal growth factor + H2O
?
-
the enzyme removes the NH2-terminal 20 amino acids by cleaving between A-83LC
-
-
?
hepatocyte growth factor activator inhibitor-1 + H2O
?
-
the 66 kDa protein is cleaved to 58, 42, and 16 kDa fragments
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
-
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
MMP14 is essential for proMMP-2 activation: pro-MMP-2 activation by MMP14/TIMP complex is realized in an environment of low TIMP concentration
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
pro-MMP-2 is cleaved by an adjacent TIMP-2-free MT1-MMP between Asn37 and Leu38, generating an activated intermediate form that is further processed to the fully activated form by an intermolecular auto-cleavage when an intermediate form is present at a sufficiently high concentration at the cell surface, mechanism, overview. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
pro-MMP-2 is cleaved by an adjacent TIMP-2-free MT1-MMP between Asn37 and Leu38, generating an activated intermediate form that is further processed to the fully activated form by an intermolecular auto-cleavage when an intermediate form is present at a sufficiently high concentration at the cell surface, mechanism, overview. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing
-
-
?
progelatinase A + H2O
?
-
syn: pro-matrix metalloproteinase 2, leads to activation of progelatinase A
-
-
?
syndecan-1 core protein + H2O
?
-
cleaves preferably at G245-L246 peptide bond
-
-
?
Type I collagen + H2O
?
-
-
669263, 678071, 678111, 679404, 680268, 680921, 681831, 681832, 682862, 638810, 669303, 734110, 734267, 734409
-
-
?
Type I collagen + H2O
?
-
cleavage of collagen by MT1-MMP regulates cell growth and invasion in a collagen-rich environment
-
-
?
Type I collagen + H2O
?
-
type I collagen binds MT1-MMP via a hemopexin-like domain and is cleaved
-
-
?
additional information
?
-
-
membrane type 1 matrix metalloproteinase activates progelatinase A, a type IV collagenase, on the cell surface of tumors. Membrane type 1-matrix metalloproteinase may play an important role in the invasive growth and spread of breast cancer cells by specifically activating pro-MMP-2 to cleave the connective-tissue barrier
-
-
-
additional information
?
-
-
role in extracellular matrix remodelling under physiological and pathological conditions
-
-
-
additional information
?
-
-
degrades components of tissue barriers, regulates cell-extracellular matrix interaction by processing cell adhesion molecules such as CD44 and integrin alpha v chain
-
-
-
additional information
?
-
-
the enzyme regulates extracellular matrix remodeling and is capable of cleaving a wide variety of transmembrane proteins. The enzymatic activity of MT1-MMP is regulated by endogenous inhibitors, TIMP, the tissue inhibitor of metalloproteinases
-
-
-
additional information
?
-
-
hydrolysis of triple helical substrates that, via addition of N-terminal alkyl chains, differ in their thermal stabilities, substitution of Cys(4-methoxybenzyl) for Leu in the P1' subsite is greatly favored by MMP-14, increase in substrate triple-helical thermal stability leads to the decreased ability of the enzyme to cleave such substrates
-
-
?
additional information
?
-
-
rat-tail tendon type I collagen not degraded by cdMT1-MMP at 37°C
-
-
?
additional information
?
-
-
MT1-MMP plays an important role in early cancer dissemination by converting epithelial cells to migratory mesenchymal-like cells
-
-
-
additional information
?
-
-
pro-alpha2 integrin subunit is not a substrate
-
-
-
additional information
?
-
-
enzyme regulation, transcription factor EGR1 is involved, overview
-
-
-
additional information
?
-
-
membrane-type MMPs are membrane spanning binding sites that play an important role in the cell surface activation of MMPs such as MMP-2
-
-
-
additional information
?
-
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities
-
-
-
additional information
?
-
-
overview of MT1-MMP-associating proteins by localization and MT1-MMP-associating membrane proteins by function. Some proteins, such as MT1-SP, EGFR, 5T4, DCP, and CD36L1, preferentially precipitate pro-MT1-MMP, other proteins, e.g. GA733-1, HAI-1, HAI-2, TF, THBD, and CD9, precipitate preferentially the active form of MT1-MMP indicating that these proteins may form a complex on the cell surface
-
-
-
additional information
?
-
-
membrane proteins were cleaved by MT1-MMP in a MMI270-sensitive manner
-
-
-
additional information
?
-
-
the enzyme does not degrade fibroblast growth factor-2 or fibroblast growth factor receptor-2
-
-
-
additional information
?
-
-
in vivo growth of FaDu cells co-injected with murine fibroblasts is increased, while their progression is reduced in MT1-MMP-deficient fibroblasts, overview
-
-
-
additional information
?
-
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities
-
-
-
additional information
?
-
-
MT1-MMP is increased in myocardial ischemia and reperfusion, and contributes to myocardial dysfunction, upstream induction mechanism by release of endothelin and protein kinase C activation, microdialysis analysis, overview
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
kidney injury molecule-1 + H2O
?
-
the enzyme cleaves and sheds the substrate's ectodomain
-
-
?
neuronal glial antigen 2 + H2O
?
Q10739
three (210, 160, and 51-52 kDa) major cleavage products are formed
-
-
?
hepatocyte growth factor activator inhibitor-1 + H2O
?
-
the 66 kDa protein is cleaved to 58, 42, and 16 kDa fragments
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
-
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
MMP14 is essential for proMMP-2 activation: pro-MMP-2 activation by MMP14/TIMP complex is realized in an environment of low TIMP concentration
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP
-
-
?
pro-MMP-2 + H2O
MMP-2 + MMP-2 propeptide
-
the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP
-
-
?
Type I collagen + H2O
?
-
cleavage of collagen by MT1-MMP regulates cell growth and invasion in a collagen-rich environment
-
-
?
additional information
?
-
-
membrane type 1 matrix metalloproteinase activates progelatinase A, a type IV collagenase, on the cell surface of tumors. Membrane type 1-matrix metalloproteinase may play an important role in the invasive growth and spread of breast cancer cells by specifically activating pro-MMP-2 to cleave the connective-tissue barrier
-
-
-
additional information
?
-
-
role in extracellular matrix remodelling under physiological and pathological conditions
-
-
-
additional information
?
-
-
degrades components of tissue barriers, regulates cell-extracellular matrix interaction by processing cell adhesion molecules such as CD44 and integrin alpha v chain
-
-
-
additional information
?
-
-
the enzyme regulates extracellular matrix remodeling and is capable of cleaving a wide variety of transmembrane proteins. The enzymatic activity of MT1-MMP is regulated by endogenous inhibitors, TIMP, the tissue inhibitor of metalloproteinases
-
-
-
additional information
?
-
-
enzyme regulation, transcription factor EGR1 is involved, overview
-
-
-
additional information
?
-
-
membrane-type MMPs are membrane spanning binding sites that play an important role in the cell surface activation of MMPs such as MMP-2
-
-
-
additional information
?
-
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities
-
-
-
additional information
?
-
-
overview of MT1-MMP-associating proteins by localization and MT1-MMP-associating membrane proteins by function. Some proteins, such as MT1-SP, EGFR, 5T4, DCP, and CD36L1, preferentially precipitate pro-MT1-MMP, other proteins, e.g. GA733-1, HAI-1, HAI-2, TF, THBD, and CD9, precipitate preferentially the active form of MT1-MMP indicating that these proteins may form a complex on the cell surface
-
-
-
additional information
?
-
-
the enzyme does not degrade fibroblast growth factor-2 or fibroblast growth factor receptor-2
-
-
-
additional information
?
-
-
in vivo growth of FaDu cells co-injected with murine fibroblasts is increased, while their progression is reduced in MT1-MMP-deficient fibroblasts, overview
-
-
-
additional information
?
-
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities
-
-
-
additional information
?
-
-
MT1-MMP is increased in myocardial ischemia and reperfusion, and contributes to myocardial dysfunction, upstream induction mechanism by release of endothelin and protein kinase C activation, microdialysis analysis, overview
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pervanadate
Zn2+
pervanadate
-
a tyrosine phosphatase inhibitor, regulates the activity of MT-MMPs, and accelerates MMP14-mediated shedding of several membrane-anchored proteins
pervanadate
-
a tyrosine phosphatase inhibitor, regulates the activity of MT-MMPs, and accelerates MMP14-mediated shedding of several membrane-anchored proteins
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-cyclopropyl-N-hydroxy-4-[(4-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]phenyl)sulfonyl]piperidine-4-carboxamide
-
-
4-([4-[4-(2-chlorophenyl)piperazin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
-
-
4-([4-[4-(2-fluorophenyl)piperazin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
-
-
4-([4-[4-(4-chlorophenyl)piperidin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
-
-
alpha1-PDX
-
completely abats MT1-MMP-induced gelatin degradation by A375 cells
-
alpha1-PIMT1
-
alpha1-proteinase inhibitor-based inhibitor by incorporating the MT1-MMP propeptide sequence into the alpha1-PI reactive-site loop, inhibits proMT1-MMP activation
-
alpha1-PIPDX
-
alpha1-proteinase inhibitor-based inhibitor with furin consensus cleavage sequence inserted into the reactive-site loop, inhibits proMT1-MMP activation
-
anti-membrane-type 1-MMP antibody
-
antibodies LEM-1 and LEM-2 inhibit endothelial cell invasion in a dose dependent manner
-
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
furin inhibitor repressing activation of MMP-2
genistein
-
markedly suppresses the VEGF mRNA induction in MT clones without affecting the VEGF expression in control clones
hemopexin
-
soluble hemopexin domain inhibits collagenolysis by preventing dimerization
-
MT1-MMP siRNA
-
collagen degrading activity is completely lost when MT1-MMP expressing cells are transfected with 100 nM MT1-MMP siRNA
-
N-hydroxy-4-([4-[4-(2-hydroxyphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(2-methoxyphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(2-methylphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(3-methoxyphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(4-methoxy-2-methylphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-([4-[4-(4-methylphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-[[4-(4-phenylpiperazin-1-yl)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxamide
-
-
N-hydroxy-4-[[4-(4-phenylpiperidin-1-yl)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxamide
-
-
N4-hydroxyamino-2-isobutyl-3-(thienylthiomethyl) succinyl]-L-phenylalamine-methylamide
-
-
Rac1(N17Rac)
-
coexpression wit MT1-MMP cDNAs leads to complete inhibition of migration
-
RO28-2653
-
reduces the VEGF mRNA levels in MT clones but does not affect the basal VEGF mRNA levels in control clones
TIMP-1
-
TIMP-1 from brain is upregulated in in the infarcted tissue compared to healthy control areas, overview
-
TIMP-1 mutant forms
-
TIMP-1(T98L), TIMP-1(V4A), TIMP-1(P6V), TIMP-1(V4S), TIMP-1(P6S), TIMP-1(M66I), TIMP-1(P6A), TIMP-1(M66V), TIMP-1(M66A), TIMP-1(T2S), TIMP-1(M66L), TIMP-1(M66G), TIMP-1(V69L), TIMP-1(M66K), TIMP-1(V4A/P6V/T98L). TIMP-1 is inactive against MT1-MMP. TIMP-1 can be transformed into an active inhibitor against MT1-MMP by the mutation T98L. The resultant mutant displays inhibitory characteristics of a slow, tight binding inhibitor. The potency of the mutant can be further enhanced by the introduction of the mutations V4A and P6V
-
tissue inhibitor of matrix metalloproteinase-1
-
i.e. TIMP-1, recombinant, human
-
BB94
-
reduces the VEGF mRNA levels in MT clones but does not affect the basal VEGF mRNA levels in control clones
DX-2400
-
represents a highly selective fully MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocks proMMP-2 processing on tumor and endothelial cells, inhibits angiogenesis and slows tumor progression and formation of metastatic lesions in xenograft models
-
DX-2400
-
represents a highly selective fully MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocks proMMP-2 processing on tumor and endothelial cells, inhibits angiogenesis and slows tumor progression and formation of metastatic lesions in xenograft models
-
DX-2400
-
represents a highly selective fully MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocks proMMP-2 processing on tumor and endothelial cells, inhibits angiogenesis and slows tumor progression and formation of metastatic lesions in xenograft models
-
DX-2400
enzyme activity is inhibited with 65.8 nM or 658 nM of the enzyme function-blocking antibody DX-2400
-
DX-2400
-
represents a highly selective fully MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocks proMMP-2 processing on tumor and endothelial cells, inhibits angiogenesis and slows tumor progression and formation of metastatic lesions in xenograft models
-
furin
-
concanavalin A-induced pro-matrix metalloproteinase 2 activation is inhibited in human uterine cervical fibroblasts, but not in rabbit dermal fibroblasts
-
furin
-
concanavalin A-induced pro-matrix metalloproteinase 2 activation is inhibited in human uterine cervical fibroblasts, but not in rabbit dermal fibroblasts
-
GM6001
-
hydroxamate inhibitor, 0.001 mM, converts protease into a cell surface receptor for receptor of complement component 1q and promotes co-precipitation of the enzyme with the soluble receptor protein
GM6001
-
fully blocks proteolysis of PA83 by MT1-MMP, inhibits MT1-MMP-dependent activation of proMMP-2
GM6001
-
blocks conversion of active 50 kDa wild type MT1-MMP to a 37 kDa species, inhibits autolysis of both wild type and CHO-4 MT1-MMP in a dose-dependent manner and with a similar inhibitory profile
marimastat
-
inhibits production of 18 kDa fragment during autocatalytic processing
TIMP-2
-
inhibits production of 18 kDa fragment during autocatalytic processing
-
TIMP-2
-
specificity of inhibitor binding of MT1-MMP, shedding of MT1-MMP ectodomain alters the balance of TIMP-2 between the cell surface and the pericellular space
-
TIMP-2
-
inhibitory interaction with the catalytically competent MT1-MMP active site, prevents autolytic processing
-
TIMP-2
-
under in vivo conditions primary inhibitor of MT1-MMP, increases endocytosis of wild type MT1-MMP
-
TIMP-3
-
during ischemia, loss of inhibitory control leading to increased MT1-MMP activity
-
TIMP-4
-
inhibits production of 18 kDa fragment during autocatalytic processing
-
TIMP-4
-
during ischemia, loss of inhibitory control leading to increased MT1-MMP activity
-
tissue inhibitor of MMP-2
-
MMP-2 activation involves tissue inhibitor of MMP-2, i.e. TIMP-2, as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. MT1-MMP auto-degradation is suppressed in the presence of TIMP-2, and MT1-MMP/TIMP-2 complex accumulates on cell surface. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing
-
tissue inhibitor of MMP-2
-
MMP-2 activation involves tissue inhibitor of MMP-2, i.e. TIMP-2, as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. MT1-MMP auto-degradation is suppressed in the presence of TIMP-2, and MT1-MMP/TIMP-2 complex accumulates on cell surface. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing
-
additional information
-
mercaptosulfide inhibitors, interacting exclusively at the enzyme active site, strong stereoselectivity at the P1' and zinc-binding groups, competitive and reverse inhibition
-
additional information
-
migration of HT1080 cells on type I collagen not supressed by TIMP-1
-
additional information
-
TIMP-1 does not block up-regulation of VEGF-A by MT1-MMP, aprotinin, Pefabloc SC, leupeptin and pepstatin A fail to modulate the VEGF expression, wortmannin, PD98059 nor SB203580 affect MT1-MMP-mediated VEGF induction
-
additional information
-
cells cotransfected with TIMP-1 cDNA along with MT1-MMP and pMMP-2 cDNAs result in partial inhibition of substrate degradation, down to the basal digestion level resulting from MT1-MMP alone, wortmannin and PD98059 do not interfer with MT1-MMP-induced cell migration, CDC42 (N17) and RhoA(N19) have no effect on MT1-MMP-dependent cell migration
-
additional information
-
not inhibited by tissue inhibitor of metalloproteinases-1
-
additional information
-
not inhibited by tissue inhibitor of metalloproteinase-1
-
additional information
-
MT1-MMP is inhibited by endogenous inhibitors TIMP-2, -3, and -4, but not by TIMP-1. MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview
-
additional information
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview
-
additional information
-
synthesis of a series of phenyl piperidine a-sulfone hydroxamate derivatives, inhibitory potencies on different MMPs, overview. No inhibition by derivatives 1-cyclopropyl-N-hydroxy-4-[[4-(4-phenylpiperazin-1-yl)phenyl]sulfonyl]piperidine-4-carboxamide, 4-([4-[4-(2,4-dimethylphenyl)piperazin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide, N-hydroxy-4-[(4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]phenyl)sulfonyl]tetrahydro-2H-pyran-4-carboxamide, N-hydroxy-4-([4-[4-(2-methoxyphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide, N-hydroxy-4-([4-[4-(2-methylphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide, 4-([4-[4-(2-chlorophenyl)piperidin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide, N-hydroxy-4-[(4-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]phenyl)sulfonyl]tetrahydro-2H-pyran-4-carboxamide, 4-([4-[4-(2-ethoxyphenyl)piperidin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide, 4-([4-[4-(4'-fluorobiphenyl-4-yl)piperidin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide, and 4-[(4-[4-[2-ethyl-5-(propan-2-yl)phenyl]piperidin-1-yl]phenyl)sulfonyl]-N-hydroxytetrahydro-2H-pyran-4-carboxamide
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cytokine
-
protein levels of the enzyme significantly increase by FGF-2 plus VEGF-A, only slightly by FGF-1, and not at all by VEGF-A
-
TAPI-1
-
leads to higher amounts of the MT1-MMP 32 kDa form in the media, also slightly increases the amount of the 50 kDa species of MT1-MMP
TIMP-2
-
required, MT-MMP1 must form a homophilic ternary complex with TIMP-2 and pro-MMP-2 to activate MMP-2
-
claudin
-
activation of matrix metalloproteinase-2 is enhanced by association with claudin
-
claudin
-
recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2
-
claudin
-
recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2
-
furin
-
activates proMT1-MMP, occurs intracellularly after exit from the Golgi apparatus and prior to its arrival at the plasma membrane
-
additional information
-
sphingosine-1-phosphate is necessary for the transactivation of the epidermal growth factor receptor by MTI-MMP
-
additional information
-
beta1 integrin clustering enhances MT1-MMP expression
-
additional information
-
membrane proteins are cleaved by MT1-MMP in a MMI270-sensitive manner
-
additional information
-
the PEX domain is required for activating cleavage activity on substrate proMMP-2 on the cell surface
-
additional information
-
MT1-MMP expression at the cell surface is increased by leptin
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00344
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2
-
pH 7.5, 37°C, mature and mutant enzyme
additional information
additional information
-
increase in substrate triple-helical thermal stability is not detrimental to enzyme binding of substrate
-
0.0000000003
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
0.00000000077
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
0.0000000027
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
0.00000032
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
0.00000000065
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
0.0000000031
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
0.0000000079
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
0.00000012
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
0.00086
collagen type I alpha-1 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.045
collagen type I alpha-1 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.12
collagen type I alpha-1 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.17
collagen type I alpha-1 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.00025
collagen type I alpha-2 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.004
collagen type I alpha-2 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.14
collagen type I alpha-2 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.53
collagen type I alpha-2 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
increase in substrate triple-helical thermal stability is detrimental to enzyme turnover of substrate
-
0.019
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
0.47
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
0.68
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
1.1
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
1.52
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
5.79
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
9.89
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
255.6
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
0.3
collagen type I alpha-1 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.43
collagen type I alpha-1 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
4.56
collagen type I alpha-1 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
10.41
collagen type I alpha-1 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.0089
collagen type I alpha-2 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
0.014
collagen type I alpha-2 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
4.09
collagen type I alpha-2 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
58.61
collagen type I alpha-2 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3400000
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
63000000
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
170000000
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
880000000
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
-1995000000
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
-1095000000
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
730000000
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
2100000000
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
2.5
collagen type I alpha-1 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
88
collagen type I alpha-1 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
100
collagen type I alpha-1 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
360
collagen type I alpha-1 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
3.5
collagen type I alpha-2 chain
-
2-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
30
collagen type I alpha-2 chain
-
4-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
110
collagen type I alpha-2 chain
-
0-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
350
collagen type I alpha-2 chain
-
1-protonated enzyme, 50 mM Tris-HCl, 0.1 M NaCl, 10 mM CaCl2 plus 0.05% Brij 35,at pH 7.3 and 37°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001 - 0.01
GM6001
-
partial blockade of autolysis of both wild type and CHO-4 mutant MT1-MMP
0.1
GM6001
-
complete blockade of autolysis of both wild type and CHO-4 mutant MT1-MMP
additional information
additional information
-
values generally lower for cdMT1-MMP when compared with those for deltaTM-MT1-MMP
-
additional information
additional information
-
between 0.000049 mM and 0.012 mM, significant decrease in inhibition potency with a homophenylalanine side chain compared with leucine, P1' substituent is interacting at the S1' pocket
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
1-cyclopropyl-N-hydroxy-4-[(4-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]phenyl)sulfonyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
4-([4-[4-(2-chlorophenyl)piperazin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
4-([4-[4-(2-fluorophenyl)piperazin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
4-([4-[4-(4-chlorophenyl)piperidin-1-yl]phenyl]sulfonyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-([4-[4-(2-hydroxyphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-([4-[4-(2-methoxyphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-([4-[4-(2-methylphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.00286
N-hydroxy-4-([4-[4-(3-methoxyphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-([4-[4-(4-methoxy-2-methylphenyl)piperidin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-([4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.00822
N-hydroxy-4-([4-[4-(4-methylphenyl)piperazin-1-yl]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-[[4-(4-phenylpiperazin-1-yl)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
0.01
N-hydroxy-4-[[4-(4-phenylpiperidin-1-yl)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxamide
Rattus norvegicus
-
pH not specified in the publication, temperature not speficied in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
MT1-MMP activity in bone tumor tissue is either no different or lower than MT1-MMP activity in control bone tissues
additional information
-
quantitative MT1-MMP expression analysis by RT-PCR, cellular invasion assay, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9.2
-
degradation of collagen I: over the whole pH range investigated the enzymatic activity toward the alpha-2 chain is significantly higher than that toward the alpha-1 chain. Difference is maximal at alkaline pH (being about 20fold at pH 9.2) and it decreases at neutral pH, such that at pH 7.3 the enzymatic processing of the alpha-2 chain is only about 5fold higher than for the alpha-1 chain
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
638795, 638796, 638797, 638799, 638800, 638801, 638802, 638803, 638804, 638805, 638806, 638807, 638808, 638809, 638810, 638811, 638812, 638813, 638814, 669303, 733033, 733570, 733605, 734110, 734243, 734267, 734297, 734362, 734409, 735036, 95831
SwissProt
brenda
-
656167, 667137, 667467, 667498, 667519, 667581, 668141, 668966, 669211, 669212, 669263, 669272, 669582, 669968, 670867, 678071, 678111, 679042, 679404, 680268, 680721, 680802, 680891, 680921, 681426, 681831, 681832, 681866, 681878, 682862, 683666, 696978, 697105, 701140, 707998, 708193, 708307, 708543, 709058, 709366, 709415, 709668, 709700, 710375, 717536, 717876, 719209, 719211, 719212, 719913, 720007, 720437, 720606, 95831, 95836, 95837
-
-
brenda
cDNA fragment coding for peptide Ala21-Ser538 of the full-length MT1-MMP
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
MMP-8 is upregulated in the infarcted tissue compared to healthy control areas
brenda
-
MMP-14 expression at fetomaternal interface of tubal pregnancy during gestational weeks 3-9, MMP-14 increases from distal column cytotrophoblast cells to invasive extravillous cytotrophoblast cells, also detected in villous cytotrophoblast cells, syncytiotrophoblast cells and some villous mesenchyma cells in varying abundance, distribution patterns of MMP-14 in villous cytotrophoblast cells and distal column cytotrophoblast cells in normal pregnancy is almost the same as that in tubal pregnancy
brenda
-
quantitative determination of content of membrane type-I MMP, TIMP-2 and MMP-2 mRNA and proteins
brenda
-
quantitative determination of content of membrane type-I MMP, TIMP-2 and MMP-2 mRNA and proteins
brenda
-
MT1-MMP is increased in myocardial ischemia and reperfusion, myocardial, interstitial enzyme, microdialysis analysis, overview
brenda
MT1-MMP is upregulated during metamorphosis and coexpressed with MMP gelatinase A in connective tissue during both natural and thyroid-hormone-induced metamorphosis, MT1-MMP is also expressed in the longitudinal muscle cells of the metamorphosing intestine
brenda
-
furin-negative cells stably expressing wild type MT1-MMP and reconstituted furin-positive cells
brenda
-
expression analysis of MMP-14 in pleural mesotheliomas compared to healthy pleural specimens, overview
brenda
-
expression in in both the epithelial and stromal elements, low enzyme activity
brenda
-
from the oral cavity, SCC9, SCC25 and SCC68 cells
brenda
-
the expression level of MTI-MMP and the catalytic activitiy of the expressed protein significantly incrases 18 h after parturition, but at postpartum day 5, the mRNA expression level and catalytic activity decrease markedly
brenda
additional information
-
isolated from the dermis of late gestation embryos in mice deficient in MT1-MMP
brenda
-
-
brenda
-
HIV1- smokers with early emphysema have significantly higher relative expression of MMP-14 in comparison with HIV1- healthy smokers and HIV1- healthy nonsmokers. HIV1+ smokers with early emphysema also have significantly higher relative expression of alveolar mucosa MMP-14 in comparison with HIV1- normal smokers and HIV1- normal nonsmokers. There is no difference between the relative expression of alveolar mucosa MMP-14 between the HIV1- smokers with early emphysema and the HIV1+ smokers with early emphysema, overview
brenda
-
cells from different carcinoma types, expression analysis, overview
brenda
-
injected into the marrow of human male fetal femurs previously implanted in SCID mice
brenda
additional information
-
not measured when PC-3 cell and bone tissue is cultured together because it is membrane-bound and not secreted into the medium
brenda
additional information
-
ovarian cancer cell lines DOV13, OVCA429, OVCA433
brenda
additional information
-
MMP-14 expression in placental villi of normal pregnancy during the first trimester
brenda
additional information
-
ductal breast cancer patients show 2fold increased serum MMP-14 levels compared to controls
brenda
additional information
-
high levels of cell surface-associated MT1-MMP and CD44 in IS-CD8+ cells
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
of immature dendritic cells. Podosomes are spot-like actin-rich structures formed at the ventral surface of monocytic and haematopoietic cells
brenda
additional information
-
expression analysis of MT1-MMP in cell culture
-
brenda
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview
brenda
-
MT1-MMP forms a homophilic complex required for activity
brenda
-
-
brenda
-
MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview
brenda
-
80% of MT1-MMP is sorted to detergent-resistant membrane fractions, only 20% of MT1-MMP from detergent-soluble fraction undergoes intracellular processing to the mature form, which is the sole form responsible for extracellular matrix degredation
brenda
-
MMP-1 localizes at membrane structures called lamellipodia and invadopodia
brenda
-
-
638795, 638797, 638802, 638804, 638812, 667498, 679404, 681426, 681831, 681832, 682862, 717536, 717876, 719209
brenda
-
shedding of membrane-tethered MT1-MMP/MMP-14 from the cell surface
brenda
-
membrane type-I MMP, like the other five membrane type MMPs, differs from other MMPs in that it has a transmembrane domain that localizes the enzyme to the plasma membrane in addition to the three basic domains that characterize all other MMPs
brenda
-
membrane type-I MMP, like the other five membrane type MMPs, differs from other MMPs in that it has a transmembrane domain that localizes the enzyme to the plasma membrane in addition to the three basic domains that characterize all other MMPs
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
loss of MMP14 activity increases steady-state vascular leakage, MMP14 activity impacts vascular leakage, mechanism, overview
malfunction
-
loss of MMP14 activity increases steady-state vascular leakage, MMP14 activity impacts vascular leakage, mechanism, overview
malfunction
-
increased levels of soluble MT1-1/MMP-14 in the serum of breast cancer patients may have implications in the pathogenesis of the disease
malfunction
-
MMP14 mediates tumor cell surface MHC class I chain-related molecule A shedding, suppression of MMP14 expression blocks MICA shedding, while overexpression of MMP14 enhances it. The regulation is independent of the activity of a disintegrin and metalloproteinases, overview
malfunction
-
MMP14 mediates tumor cell surface MHC class I chain-related molecule A shedding, suppression of MMP14 expression blocks MICA shedding, while overexpression of MMP14 enhances it. The regulation is independent of the activity of a disintegrin and metalloproteinases, overview
malfunction
-
membrane-type 1 matrix metalloproteinase knockdown in DU-145 cells decreases activity of reactive oxygen species 8-hydroxydeoxyguanosine
malfunction
MT1-MMP inhibition restores sensory axon regeneration and attenuates hypersensitivity caused by peripheral nerve injury
metabolism
-
type I collagen fibrils posttranslationally regulate perivascular MMP activity and TGFbeta bioavailability, which in turn regulate vascular homeostasis by altering vessel stability and leakage. Matrix metalloproteinase 14 and transforming growth factor beta 1 are involved in a pathway regulating vessel stability in tissues, the pathway mediates vessel stability and vascular response to tissue injury
metabolism
-
type I collagen fibrils posttranslationally regulate perivascular MMP activity and TGFbeta bioavailability, which in turn regulate vascular homeostasis by altering vessel stability and leakage. Matrix metalloproteinase 14 and transforming growth factor beta 1 are involved in a pathway regulating vessel stability in tissues, the pathway mediates vessel stability and vascular response to tissue injury
metabolism
-
MMP-14 is involved in gene network of deregulated genes associated to cell cycle, overview
metabolism
-
cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase
physiological function
-
tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities. MT1-MMP plays an essential role in angiogenesis, CD151 may contribute to endothelial homeostasis through the regulation of MT1-MMP. CD9, CD81, and TSPAN12 also associate with cell surface molecules including integrins. Tetraspanin-regulated cell surface localization of MT1-MMP increases the local concentration for focal proteolysis within the pericellular environment and leads to efficient extracellular matrix degradation and MMP-2 activation
physiological function
-
an essential role for MT1-MMP in the process of angiogenesis and bone growth. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities. MT1-MMP plays an essential role in angiogenesis, CD151 may contribute to endothelial homeostasis through the regulation of MT1-MMP. CD9, CD81, and TSPAN12 also associate with cell surface molecules including integrins. Tetraspanin-regulated cell surface localization of MT1-MMP increases the local concentration for focal proteolysis within the pericellular environment and leads to efficient extracellular matrix degradation and MMP-2 activation
physiological function
-
MMP14 regulates TGFbeta bioactivity and vascular stability, MMP14 also regulates the bioavailability of several chemokines and growth factors. MMP14-mediated resistance to vascular and VEGF leakage is accompanied by decreased appearance of leakage sites in vessels with perivascular cell coverage
physiological function
-
membrane-type 1 matrix metalloproteinase 1 is a potent modulator of the pericellular microenvironment and regulates cellular functions in physiological and pathological settings in mammals. MT1-MMP mediates its biological effects through cleavage of specific substrate proteins. Cleavage of collagen by MT1-MMP regulates cell growth and invasion in a collagen-rich environment
physiological function
-
podosomes mediate migration of dendritic cells through tissues by means of myosin-II-dependent protrusion coupled to MMP-14-dependent degradation and endocytosis. Degradation, protrusion and endocytosis in this system are dependent on the matrix metalloproteinase MMP-14
physiological function
-
MT-MMP1 must form a homophilic ternary complex with TIMP-2 and pro-MMP-2 to activate MMP-2
physiological function
-
in endothelial cells, MMP-14 is the main endoglin shedding protease
physiological function
-
the processing of heparin-binding epidermal growth factor by MT1-MMP converts the substrate into a heparin-independent growth factor with enhanced mitogenic activity, and thereby, expression of both proteins costimulates tumor cell growth in vitro and in vivo
physiological function
-
the processing of heparin-binding epidermal growth factor by MT1-MMP converts the substrate into a heparin-independent growth factor with enhanced mitogenic activity, and thereby, expression of both proteins costimulates tumor cell growth in vitro and in vivo
physiological function
-
MT1-MMP coexpressed with heparin-binding epidermal growth factor in ovarian carcinoma cells potentiates the activity of heparin-binding epidermal growth factor to promote invasive tumor growth and spreading in vivo. MT1-MMP promotes heparin-binding epidermal growth factor-dependent proliferation of ovarian carcinoma cells
physiological function
-
oxidative stress and prostate cancer progression are elicited by membrane-type 1 matrix metalloproteinase
physiological function
-
overexpression of MT1-MMP induces epithelial-to-mesenchymal transition and results in the acquisition of cancer stem cell-like properties in SCC-9 cells. Upon up-regulation of the enzyme, the cells undergo EMT, in which they presented a fibroblast-like phenotype and have a decreased expression of epithelial markers (E-cadherin, cytokeratin18 and beta-catenin) and an increased expression of mesenchymal markers (vimentin and fibronectin)
physiological function
-
the enzyme promotes cancer cell invasion. The MT-LOOP-dependent enzyme localization to the cell adhesion complex promotes cellular invasion (the MT-LOOP is a region in the catalytic domain of MT1-MMP (163PYAYIREG170))
physiological function
-
activated hepatic stellate cells require membrane type 1 matrix metalloproteinase-cleaved collagen for their survival
physiological function
-
the enzyme promotes Notch1 activation in melanoma cells
physiological function
both neuronal glial antigen 2 shedding and axonal growth depend on the pericellular remodeling executed by MT1-MMP/MMP-14
physiological function
-
in tumor cells the enzyme downregulates fibroblast growth factor-2 signaling by reducing the amount of fibroblast growth factor-2 signaling bound to the cell surface with high and low affinity
physiological function
membrane type 1 matrix metalloproteinase-dependent activation of MMP-2 is required for optimal neurite outgrowth
physiological function
-
the enzyme promotes tumor progression by circumventing the collagen-induced up-regulation of the pro-apoptotic tumor suppressor BIK. The enzyme contributes to the inactivation of the DDR1-BIK signalling axis through the cleavage of collagen fibres and/or the alteration of DDR1 receptor signalling unit, without triggering a drastic remodelling of the transcriptome of MCF-7 cells
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
G0R1A0_ICHMG
Ichthyophthirius multifiliis (strain G5)
555
0
65974
TrEMBL
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
18000
-
immunoblot analysis of untreated cells, soluble MT1-MMP species, product of autocatalytic processing
27000
-
immunoblot analysis of cells regardless of TAPI-1 treatment, contains haemopexin-like domain, formed by autocatalytic processing of the 57 kDa active form
50000
53000
55000
57000
60000
62000
63000
65000
-
immunoprecipitation, post-translationally modified unprocessed form, glycopeptidase F-resistant and also present if treated with inhibitors of N- and O-glycosylation
66000
70000
53000
-
immunoblot analysis, species of MT1-MMP isolated from a non-detergent extract of human breast carcinoma tissue, lack of the cytosolic tail
57000
-
immunoblot analysis of cells treated with TAPI-1, membrane anchored fragment shed in membrane vesicles
63000
-
full length pro-form, SDS-PAGE; inactive form after treatment with concanavalin A or cytochalasin D, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
-
homodimerization of MT1-MMP through its hemopexin domain is essential for cleaving type I collagen fibers at the cell surface
multimer
additional information
additional information
-
membrane type-I MMP, like the other five membrane type MMPs, differs from other MMPs in that it has a transmembrane domain that localizes the enzyme to the plasma membrane in addition to the three basic domains that characterize all other MMPs
additional information
-
dimer formation is specific to the PEX domain of MT1-MMP, the PEX domain of MT4-MMP does not substitute for it
additional information
-
membrane type-I MMP, like the other five membrane type MMPs, differs from other MMPs in that it has a transmembrane domain that localizes the enzyme to the plasma membrane in addition to the three basic domains that characterize all other MMPs
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
glycosylation and palmitoylation of Cys 564 in the cytosolic tail
proteolytic modification
ubiquitination
-
MT1-MMP is mono-ubiquitinated intracellularly at K581 within the short intracellular domain by NEDD-4. This post-translational modification is involved in MT1-MMP trafficking as well as in modulating cellular invasion through type-I collagen matrices. Ubiquitination is regulated by Src-mediated phosphorylation of MT1-MMP
proteolytic modification
-
pro-Mt-MMP-1 mutants are efficiently processed to active proteinases following post-translational endoproteolysis immediately downstream of an Arg108-Arg-Lys-Arg basic motif by a proprotein convertase-dependent pathway
proteolytic modification
trace amounts of active enzyme induce activation of the zymogen and its self-proteolysis. This autocatalytic processing generates six main forms of MT1-MMP. The enzyme functions as a self-convertase and is capable of cleaving its own prodomain at the furin cleavage motif RRKR-/-Y112, thus autocatalytically generating the mature MT1-MMP enzyme with an N-terminus starting at Tyr112. The mature enzyme undergoes further autocatalysis to the two distinct intermediates, N-terminus at Trp119 and at Asn130, and next to the three inactive ectodomain forms (N-terminus at Thr222, at Gly284, and at Thr299)
proteolytic modification
-
proMMP-14 detected at 63000 Da, processed form at 57000 Da using SDS-PAGE
proteolytic modification
-
MT-MMPs have a unique regulatory mechanism in which an active enzyme undergoes a series of processing steps, either autocatalytic or mediated by other proteases, that regulate the activity and nature of the enzyme species at the cell surface and at the pericellular space
proteolytic modification
-
MMPs zymogen activation is strictly controlled by a membrane-associated event strictly connecting MT-MMP and MMP functions
proteolytic modification
-
furin processes MT1-MMP to its active form, inhibited by synthetic peptidyl chloromethyl ketones
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
2.75 A crystal structure of the complex between the catalytic domain of human membrane type 1-matrix metalloproteinase and bovine tissue inhibitor of metalloproteinase
-
sitting drop vapor diffusion method, using 0.1 M sodium malonate pH 4.0, 20% (w/v) PEG 3350, or 4% (v/v) tacsimate pH 6.0, 12% (w/v) PEG 3350, or 0.2 M ammonium nitrate, 20% (w/v) PEG 3350 pH 6.2
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C574A
-
inefficient in stimulating cell adhesion, migration and invasion, mutation negatively affects cell adhesion
C574S
-
substitution in the cytoplasmic domain, reduction of pro-MMP2 activation, no up-regulation of VEGF expression
E240A
K44A
-
dominant negative dynamin mutation controlled by a separate cytomegalovirus promoter MT1/K44A, leading to increased substrate digestion that is contributed by enhanced cell migration resulting from the accumulation of MT1-MMP ant the plasma membrane
L571A/L572A/Y573A
-
mutation leads to reduced internalization of enzyme, no effect on cell motility
S577A
T567A
-
substitution in the cytoplasmic domain, pro-MMP2-activating capacity not affected, similar VEGF upregulation
Y573A