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Information on EC 3.4.24.80 - membrane-type matrix metalloproteinase-1 and Organism(s) Homo sapiens
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Word Map
- 3.4.24.80
- metalloproteinases
- mmp-2
- metastasis
- endothelial
-
zymography
- angiogenesis
- gelatin
- gelatinase
- timps
- prommp-2
- mesenchymal
-
invasiveness
- vessel
-
basement
- integrins
-
angiogenic
- fibrosarcoma
- matrigel
-
transwell
- furin
- fibronectin
- zymogen
-
gelatinolytic
- progelatinase
- ectodomain
-
invadopodia
- hemopexin
- alphavbeta3
- proproteins
-
mt-mmps
-
collagen-rich
-
anti-invasive
-
matrix-degrading
-
collagenolytic
-
pro-matrix
-
emmprin
-
hemopexin-like
-
membrane-tethered
- proenzyme
-
convertase
-
invasion-promoting
- analysis
- diagnostics
-
cona-induced
- medicine
- drug development
- endoglin
- reck
- podosomes
-
mmp-dependent
- cortactin
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected 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
mmp14, membrane-type 1 matrix metalloproteinase, membrane type 1 matrix metalloproteinase, membrane type-1 matrix metalloproteinase, membrane type 1-matrix metalloproteinase, matrix metalloproteinase 14, membrane type 1-mmp, mt-mmp-1, matrix metalloproteinase-14, membrane type 1 mmp, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
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
membrane type 1-matrix metalloproteinase
membrane type-1 matrix metalloprotease 1
-
-
-
-
membrane type-1 matrix metalloproteinase
membrane-type 1 matrix metalloproteinase
membrane-type matrix metalloproteinase MT1-MMP
-
-
-
-
membrane-type metalloproteinase MT1-MMP
-
-
-
-
MMP-14
MMP14
MT-MMP-1
-
-
-
-
MT-MMP1
MT1-MMP
proteinase, matrix metallo-
-
-
-
-
matrix metalloproteinase 14
-
-
-
-
membrane type 1 matrix metalloproteinase
-
-
-
-
membrane type 1 matrix metalloproteinase
-
-
membrane type 1 matrix metalloproteinase
-
membrane type 1-matrix metalloproteinase
-
-
membrane-type 1 matrix metalloproteinase
-
-
MMP-14
-
-
-
-
MMP-14
-
-
MT-MMP1
-
-
-
-
MT1-MMP
-
-
-
-
MT1-MMP
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
-
-
-
-
hydrolysis
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
161384-17-4
-
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
((Gly-Pro-4-hydroxyproline)5-Gly-Pro-Lys(7-methoxycoumarin-4-yl) acetyl)-Gly-Pro-Gln-Gly-Cys(4-methoxybenzyl)-Arg-Gly-Gln-Lys(2,4-dinitrophenyl)-Gly-Val-Arg-(Gly-Pro-4-hydroxyproline)5-NH2 + H2O
?
triple-helical substrate fTHP-9
-
-
?
(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-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-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
?
-
-
-
-
?
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 + H2O
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly + Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
triple-helical substrate fTHP-9
-
-
?
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)
-
-
?
CCN3 + H2O
CPPQCPGR + DGQIGCVPR + KVEVPGECCEK + KPVMVIGTCTCHTNCPK + ?
-
-
-
?
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
-
-
?
dabcyl-Gly-Gly-Pro-Gln-Gly-Ile-Trp-Gly-Gln-Lys(fluorescein)-Ahx-Cys + H2O
?
-
-
-
?
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 + ?
-
-
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
-
-
?
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
heparin-binding epidermal growth factor mN3-fragment + ?
-
-
-
-
?
inactive pro-matrix metalloproteinase-2 + H2O
active matrix metalloproteinase-2 + ?
-
-
-
-
?
kidney injury molecule-1 + H2O
?
the enzyme cleaves and sheds the substrate's ectodomain
-
-
?
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2 + H2O
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly + Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
-
-
-
?
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
-
-
-
-
?
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
?
-
-
-
?
(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
?
-
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
?
-
rat-tail tendon type I collagen boiled for 5 min and denatured to gelatin, when degraded by deltaTM-MT1-MMP and cdMT1-MMP
-
-
?
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
-
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
-
-
?
progelatinase A + H2O
?
syn: pro-matrix metalloproteinase 2, leads to activation of progelatinase A
-
-
?
progelatinase A + H2O
?
-
syn: pro-matrix metalloproteinase 2, leads to activation of progelatinase A
-
-
?
progelatinase A + H2O
?
syn: pro-matrix metalloproteinase 2, leads to activation of progelatinase A
-
-
?
progelatinase A + H2O
?
-
syn: pro-matrix metalloproteinase 2, leads to activation of progelatinase A
-
-
?
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
-
-
?
transglutaminase + H2O
?
tissue transglutaminase that binds fibronectin
-
-
?
Type I collagen + H2O
?
-
-
-
-
?
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
?
-
-
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
?
-
interaction analysis of MMP14 with proteins in HeLa cells identified by inactive catalytic domain capture yeast 2-hybrid analysis, overview. Detection of CCN5 as a MMP14 substrate by yeast 2-hybrid screening
-
-
?
additional information
?
-
CCN = cysteine rich protein 61/connective tissue growth factor/nephroblastoma overexpressed
-
-
?
additional information
?
-
modeling of enzyme-substrate interaction
-
-
?
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
-
-
?
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
-
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
-
-
?
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
?
-
-
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
?
-
interaction analysis of MMP14 with proteins in HeLa cells identified by inactive catalytic domain capture yeast 2-hybrid analysis, overview. Detection of CCN5 as a MMP14 substrate by yeast 2-hybrid screening
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
pervanadate
-
a tyrosine phosphatase inhibitor, regulates the activity of MT-MMPs, and accelerates MMP14-mediated shedding of several membrane-anchored proteins
Zn2+
additional information
preparation of apo-MT1-MMP (metal-free material) and preparation of Co2+-MT1-MMP. Co2+-MMP-1 is obtained by removal of the native metal dialyzing against o-phenanthroline and successively addition of cobalt salt, method overview
Zn2+
zinc-dependent endopeptidase, enzyme inactivation by removal of the active site Zn2+ by dialysis
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-2-[[(4'-methoxybiphenyl-4-yl)sulfonyl](propan-2-yloxy)amino]butanamide
-
(2R)-4-(acetylamino)-2-[(biphenyl-4-ylsulfonyl)amino]-N-hydroxybutanamide
-
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
-
bone marrow stromal cell antigen 2
best-2, interaction with MT1-MMP via the cytoplasmic tails of both. Bst-2 inhibits the release of virus from infectious cells and this inhibition can be reversed by MT1-MMP. Bst-2 tetherin activity is blocked by MT1-MMP
-
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,N'-bis(4-[[(3R)-3-[(biphenyl-4-ylsulfonyl)amino]-4-(hydroxyamino)-4-oxobutyl]amino]-4-oxobutyl)benzene-1,3-dicarboxamide
-
N,N'-bis[(3R)-3-[(biphenyl-4-ylsulfonyl)amino]-4-(hydroxyamino)-4-oxobutyl]benzene-1,3-dicarboxamide
-
N,N'-bis[4-[(2-[[(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]amino]ethyl)amino]-4-oxobutyl]benzene-1,3-dicarboxamide
-
N-(2-[[(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]amino]ethyl)-N'-(2-[[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]
modelling ofcompound 6 binding to dimeric MT1-MMP (catalytic domains)
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 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
-
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
-
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-4
inhibits production of 18 kDa fragment during autocatalytic 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
design, synthesis, and biological evaluation of bifunctional inhibitors of membrane type 1 matrix metalloproteinase (MT1-MMP), overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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
collagen I up-regulates both MT1-MMP gene and functions in various cell types
-
additional information
-
collagen I up-regulates both MT1-MMP gene and functions in various cell types
-
additional information
MMP14 requires removal of an N-terminal pro-domain sequence for its activation
-
additional information
-
MMP14 requires removal of an N-terminal pro-domain sequence for its activation
-
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
0.0151 - 0.0368
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
-
0.0006 - 0.0028
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
0.0151
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme
-
0.0186
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant soluble enzyme
-
0.0234
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain
-
0.0368
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain
-
0.0003
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
0.00077
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
0.0027
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
0.32
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
0.00065
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
0.0031
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
0.0079
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
0.12
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
-
3-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
-
3-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
-
0.0006
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 10°C, recombinant enzyme
0.0018
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 25°C, recombinant enzyme
0.0021
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 30°C, recombinant enzyme
0.0028
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 37°C, recombinant enzyme
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
increase in substrate triple-helical thermal stability is not detrimental to enzyme binding of substrate
-
additional information
additional information
steady-state kinetics and thermodynamics over a wide range of temperatures and pressures, stopped-flow fluorescence technique
-
additional information
additional information
-
steady-state kinetics and thermodynamics over a wide range of temperatures and pressures, stopped-flow fluorescence technique
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.14 - 0.84
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
-
0.33 - 6.8
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
additional information
additional information
-
increase in substrate triple-helical thermal stability is detrimental to enzyme turnover of substrate
-
0.14
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme
-
0.2
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain
-
0.21
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain
-
0.84
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant soluble enzyme
-
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
-
0.33
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 10°C, recombinant enzyme
2.1
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 25°C, recombinant enzyme
3.4
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 30°C, recombinant enzyme
6.8
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 37°C, recombinant enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.44 - 45.2
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
-
550 - 2429
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
5.44
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain
-
8.97
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain
-
9.27
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme
-
45.2
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
pH not specified in the publication, 37°C, recombinant soluble enzyme
-
3.4
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
63
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
170
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-protonated
-
880
collagen I alpha-1 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
730
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 1-protonated
-
2100
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 2-protonated
-
2300
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 3-protonated
-
3200
collagen I alpha-2 chain
-
pH not specified in the publication, 37°C, MMP-1: 0-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
-
O-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
-
O-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
-
550
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 10°C, recombinant enzyme
1167
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 25°C, recombinant enzyme
1619
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 30°C, recombinant enzyme
2429
methoxycoumarin-4-acetyl-Lys-Pro-Leu-Gly-Leu-Lys(2,4-dinitrophenyl)-Ala-Arg-NH2
pH 7.0, 37°C, recombinant enzyme
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
-
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
-
additional information
additional information
-
values generally lower for cdMT1-MMP when compared with those for deltaTM-MT1-MMP
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000039
(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-2-[[(4'-methoxybiphenyl-4-yl)sulfonyl](propan-2-yloxy)amino]butanamide
Homo sapiens
pH 7.5, 37°C
0.000034
(2R)-4-(acetylamino)-2-[(biphenyl-4-ylsulfonyl)amino]-N-hydroxybutanamide
Homo sapiens
pH 7.5, 37°C
0.000041
N,N'-bis(4-[[(3R)-3-[(biphenyl-4-ylsulfonyl)amino]-4-(hydroxyamino)-4-oxobutyl]amino]-4-oxobutyl)benzene-1,3-dicarboxamide
Homo sapiens
pH 7.5, 37°C
0.00008
N,N'-bis[(3R)-3-[(biphenyl-4-ylsulfonyl)amino]-4-(hydroxyamino)-4-oxobutyl]benzene-1,3-dicarboxamide
Homo sapiens
pH 7.5, 37°C
0.000007
N,N'-bis[4-[(2-[[(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]amino]ethyl)amino]-4-oxobutyl]benzene-1,3-dicarboxamide
Homo sapiens
pH 7.5, 37°C
0.000014
N-(2-[[(2R)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]amino]ethyl)-N'-(2-[[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl][(4'-methoxybiphenyl-4-yl)sulfonyl]
Homo sapiens
pH 7.5, 37°C
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
SwissProt
-
-
-
-
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
-
-
-
733033, 733570, 733605, 734110, 734243, 734267, 734297, 734362, 734409, 735036, 752872, 752971, 753019, 753242, 753773, 753776, 753906, 754158, 754591, 755009, 755435, 761331
SwissProt
cDNA fragment coding for peptide Ala21-Ser538 of the full-length MT1-MMP
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
MMP-8 is upregulated in the infarcted tissue compared to healthy control areas
-
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
-
quantitative determination of content of membrane type-I MMP, TIMP-2 and MMP-2 mRNA and proteins
-
furin-negative cells stably expressing wild type MT1-MMP and reconstituted furin-positive cells
-
expression analysis of MMP-14 in pleural mesotheliomas compared to healthy pleural specimens, overview
-
from the oral cavity, SCC9, SCC25 and SCC68 cells
primary human trophoblasts from 50 first trimester placentas (gestational week 7-12), high MMP115 expression
additional information
mRNA and protein levels of MMP14 are increased in gastric cancer cell. Upregulation of matrix metalloproteinase-14 expression contributes to metastatic properties of gastric cancer. MMP14 expression is related to advanced TNM stage, tumor grade, and lymph node metastasis. High expression of MMP14 and CDK7 are independent prognostic factors for overall survival in patients with gastric cancer
-
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
-
cells from different carcinoma types, expression analysis, overview
-
injected into the marrow of human male fetal femurs previously implanted in SCID mice
additional information
-
MMP-14 expression in placental villi of normal pregnancy during the first trimester
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
additional information
-
ductal breast cancer patients show 2fold increased serum MMP-14 levels compared to controls
additional information
MT1-MMP is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells
additional information
-
MT1-MMP is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
-
-
-
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
-
MMP-1 localizes at membrane structures called lamellipodia and invadopodia
membrane-type matrix metalloproteinase 1 is a type I membrane protein
-
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
-
shedding of membrane-tethered MT1-MMP/MMP-14 from the cell surface
additional information
MMP14 encodes a membrane-bound metalloprotease that requires removal of an N-terminal pro-domain sequence for its activation and presentation at the cell surface. In vitro modelling for assessing MMP14 processing and subcellular localization
-
additional information
-
MMP14 encodes a membrane-bound metalloprotease that requires removal of an N-terminal pro-domain sequence for its activation and presentation at the cell surface. In vitro modelling for assessing MMP14 processing and subcellular localization
-
additional information
quantitative assessment of MT1-MMP cell surface-associated proteolytic activity compared to soluble activity. MT1-MMP activity (kcat/KM) on the cell surface is 4.8fold lower compared with soluble MT1-MMP, with the effect largely manifested in kcat. Deletion of the MT1-MMP cytoplasmic tail enhances cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin-like domain negatively impacts KM and increases kcat. Cell surface localization of MT1-MMP restricts substrate binding and protein-coupled motions (based on changes in both kcat and KM) for catalysis
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
membrane-type matrix metalloproteinase 1 (MT1-MMP, also MMP14) is a type I membrane protein belonging to the MT-MMP family
malfunction
metabolism
physiological function
additional information
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
-
loss of MMP14 activity increases steady-state vascular leakage, MMP14 activity impacts vascular leakage, mechanism, 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
a single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) results in lower enzyme activation by bicelles
malfunction
deletion of the MT1-MMP cytoplasmic tail enhances cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin-like domain negatively impacts KM and increases kcat
malfunction
functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome (WS) phenotype. The WS phenotype includes craniofacial malformations, kyphosis, short-stature, and reduced bone density owing to defective collagen remodeling
metabolism
-
MMP-14 is involved in gene network of deregulated genes associated to cell cycle, overview
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
an MT1-MMP/Notch1 signaling pathway supports melanoma cell growth
metabolism
cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase
metabolism
CCN5 (WISP2) is processed in the variable region by MMP14 and MMP2, as well as by MMP1, 3, 7, 8, 9 and 15. CCN5 cleavage by proangiogenic MMPs results in removal of an angiogenic brake held by CCN5. CCN3 is processed most efficiently by MMP14, 2 and 1 from about 30 kDa to fragments of 20-25 kDa, and less efficiently by MMP8 and 9
metabolism
matrix metalloproteinases (MMP) are an important family of proteases which catalyze the degradation of extracellular matrix components
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
-
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
-
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
-
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
-
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
activated hepatic stellate cells require membrane type 1 matrix metalloproteinase-cleaved collagen for their survival
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
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
the enzyme promotes Notch1 activation in melanoma cells
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
physiological function
cell surface localization of MT1-MMP restricts substrate binding and protein-coupled motions (based on changes in both kcat and KM) for catalysis
physiological function
collagen degradation and proMMP-2 activation are major functions of MT1-MMP to promote cancer cell invasion. Both processes require MT1-MMP homodimerization on the cell surface
physiological function
enzyme MT1-MMP plays a crucial role in many physiological and pathological processes, especially in tumor invasion and metastasis
physiological function
membrane type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane cell-surface protease that has been implicated in numerous pathologies. The pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple helices occurs within blades I and II of this domain. MT1-MMP collagenolytic activity appears critical for transmigration of tumor cells, endothelial cells, and fibroblasts through collagen matrices, while post-myocardial infarction survival has been correlated to the collagenolytic potential of cardiac fibroblasts, where MT1-MMP is the dominant collagenase within myocardial tissues
physiological function
membrane type 1-matrix metalloproteinase (MT1-MMP or MMP-14) is involved in the degradation of extracellular matrix and tumor invasion. MT1-MMP is involved in the mediation of pericellular proteolysis of extracellular matrix components, essential for the physiological remodeling processes such as tissue repair, development, and morphogenesis. MT1-MMP is overexpressed in many cancer types and increases tumor cell growth, invasion, and metastasis by degrading extracellular matrix components and making paths through surrounding tissues
physiological function
membrane type-1 matrix metalloproteinase (MT1-MMP) plays a pivotal role in cellular growth and migration by activating proMMP-2 into active MMP2. MT1-MMP inhibits the tetherin activity of Bst-2 (bone marrow stromal cell antigen 2), a type II membrane protein, by interacting with Bst-2, not via downregulation of Bst-2. The cytoplasmic domains of both Bst-2 and MT1-MMP play critical roles within this interaction. Bst-2 inhibits MT1-MMP activity through their interaction resulting in a decrease of proMMP2 activation
physiological function
MMP14 is a regulator of angiogenesis, it cleaves CCN5 and abrogates the angiostatic activity. CCN5 is an angiogenesis inhibitor that is inactivated by MMP14 cleavage. Proteolytic processing of CCN3 by MMP14
physiological function
the cell-surface collagen degradation by MT1-MMP involves DDR2-mediated collagen signaling
additional information
a small conformational change is detected at 37°C, which is responsible for the change in activity observed at the same temperature. Pressure decreases the enzymatic activity until complete inactivation occurs at 2 kbar. The inactivation is associated with changes in the rate-limiting step of the reaction caused by additional hydration of the active site upon compression and/or minor conformational changes in the active site region
additional information
-
a small conformational change is detected at 37°C, which is responsible for the change in activity observed at the same temperature. Pressure decreases the enzymatic activity until complete inactivation occurs at 2 kbar. The inactivation is associated with changes in the rate-limiting step of the reaction caused by additional hydration of the active site upon compression and/or minor conformational changes in the active site region
additional information
an initial structural framework defines the role(s) of cell membranes in modulating proteolysis. Examination of simultaneous membrane interaction and triple-helix binding reveals a possible regulation of proteolysis due to steric effects of the membrane. Activity analysis of MT1-MMP in membrane-like environments, Interaction of the isolated 15N MT1-MMP HPX domain with bilayers, with a collagen-like triple helical peptide (THP) alone or in the presence of bicelles, or with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), interaction of 15N sMT1-MMP with bicelles, NMR spectroscopic analysis, modelling, overview
additional information
DDRs are receptor tyrosine kinases (RTKs) in which phosphorylation of their cytoplasmic domain is induced by binding to collagen at their ectodomain. Discoidin domain receptor 2 (DDR2) mediates type I collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts. Knocking down DDR2, but not the beta1 integrin subunit, a common subunit for all collagen-binding integrins, inhibits the collagen-induced MT1-MMP-dependent activation of pro-MMP-2 and upregulation of MT1-MMP at the gene and protein levels. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells, as collagen-induced MT1-MMP activation in HT-1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells are not affected by DDR kinase inhibition
additional information
-
DDRs are receptor tyrosine kinases (RTKs) in which phosphorylation of their cytoplasmic domain is induced by binding to collagen at their ectodomain. Discoidin domain receptor 2 (DDR2) mediates type I collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts. Knocking down DDR2, but not the beta1 integrin subunit, a common subunit for all collagen-binding integrins, inhibits the collagen-induced MT1-MMP-dependent activation of pro-MMP-2 and upregulation of MT1-MMP at the gene and protein levels. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells, as collagen-induced MT1-MMP activation in HT-1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells are not affected by DDR kinase inhibition
additional information
solvent water interactions within the active site of the membrane type I matrix metalloproteinase, crystal structure analysis, quantum mechanics/molecular mechanics geometries and modelling, structure modelling, overview
additional information
the catalytic domain comprises residues Tyr112-Gly284
additional information
visualization of membrane-bound, active MT1-MMP is achieved by fluorescence resonance energy transfer (FRET) imaging of surface-anchored sensors. An initial MT1-MMP sensor was created using the Cys-Pro-Lys-Glu-Ser-Cys-Asn-Leu-Phe-Val-Leu-Lys-Asp sequence, derived from the MT1-MMP cleavage site in proMMP-2. The C-terminus plays a required role in regulating proteolytic activity at the cell surface
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MMP14_HUMAN
582
1
65894
Swiss-Prot
Secretory Pathway (Reliability: 1)
K4RH61_HUMAN
582
1
65949
TrEMBL
Secretory Pathway (Reliability: 2)
B2R6P3_HUMAN
582
1
65849
TrEMBL
Secretory Pathway (Reliability: 1)
A0A7P0TAG0_HUMAN
503
0
56929
TrEMBL
Secretory Pathway (Reliability: 1)
B7Z747_HUMAN
594
0
66180
TrEMBL
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
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
54000
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
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
inactive form after treatment with concanavalin A or cytochalasin D, SDS-PAGE
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
multimer
non-denaturating conditions, enzyme exists as a dimer or mulitmer
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
enzyme MT1-MMP possesses a multidomain structure, encompassing a signal peptide, propeptide, catalytic (CAT) domain, hinge region (linker 1), hemopexin-like (HPX) domain, stalk region (linker 2), transmembrane domain (TM), and cytoplasmic tail (CT)
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
-
MMPs zymogen activation is strictly controlled by a membrane-associated event strictly connecting MT-MMP and MMP functions
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
discoidin domain receptor 2 (DDR2) mediates collagen I-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts
proteolytic modification
MMP14 requires removal of an N-terminal pro-domain sequence for its activation and presentation at the cell surface. The pro-domain has two furin cleavage motifs, R89-R-P-R-C93 and R108-R-K-R-Y112
proteolytic modification
MT1-MMP is activated by incubation of pro-sMT1-MMP with rhtrypsin-3 and cleavage of the propeptide
proteolytic modification
MT1-MMP is activated by incubation of the proMT-MMP with rhTrypsin-3 for 1 hr at 37°C
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
-
purified recombinant His-tagged apoenzyme and Zn2+-MT1-MMP, X-ray diffraction structure determination and analysis at 2.24-2.88 A resolution, modelling with bound substrate peptide IAG
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C127S
site-directed mutagenesis, no significant difference in activity is observed for the mutant C127S and the wild-type MT1-MMP
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/L578A/L579A
mutation leads to reduced internalization of enzyme
L571A/L572A/Y573A
mutation leads to reduced internalization of enzyme, no effect on cell motility
R111H
site-directed mutagenesis, MMP14 R111H enzyme is processed normally in human MRC-5V1 cells and is trafficked to the cell surface, the mutation partially impairs the catalytic activity of MMP14, thus MMP14 R111H retains partial gelatinolytic and pro-MMP2 hydrolyzing activity. The mutant demonstrates significantly reduced migratory behavior when compared with wild-type MMP14
R92C
site-directed mutagenesis, the mutation impairs cell surface localization. The mutant demonstrates significantly reduced migratory behavior when compared with wild-type MMP14
S466P
S577A
T17R
site-directed mutagenesis, the mutation impairs cell surface localization, MMP14 T17R distributed throughout the cytoplasm. The mutant demonstrates significantly reduced migratory behavior when compared with wild-type MMP14
T567A
-
substitution in the cytoplasmic domain, pro-MMP2-activating capacity not affected, similar VEGF upregulation
Y573A
Y573A/L571A/L572A/L578A/L579A
mutation leads to reduced internalization of enzyme
additional information
E240A
catalytically inactive, inefficient in stimulating cell migration and invasion
E240A
-
substitution in the active site, unable to activate exogenous pro-MMP2, fails to induce VEGF mRNA expression
S466P
site-directed mutagenesis, the mutation impairs cell surface localization
S577A
-
substitution in the cytoplasmic domain, pro-MMP2-activating capacity not affected, similar VEGF upregulation
additional information
catalytic domain: TM1 MMPcat, DELTA269-550 and deletion of transmembrane and cytoplasmic domain: DELTA TM MT1 MMP, DELTA501-559
additional information
mutant defective in catalytic domain, deletion of transmembrane/cytoplasmic domain, deletion of hemopexin domain abolishes enzyme activity, whereas substitution of transmembrane/cytoplasmic membrane with Il-2 receptor does not affect it
additional information
truncation mutant MT1DELTAC with more robust pro-MMP-2 activation and cell surface expression than wild type enzyme, mutant is resistant to increased cell surface expression after concanavalin A treatment
additional information
deletions delta Cat or point mutations CHO-1 and CHO-4, which preserve a relative electrophoretic mobility shift following desialylation similar to the wild type protein, moreover mutant CHO-4 is insensitive to sialidase A treatment, CHO-3 and CHO-4 mtuants are unable to effectively catalyze pro-MMP-2 activation
additional information
-
deletions delta Cat or point mutations CHO-1 and CHO-4, which preserve a relative electrophoretic mobility shift following desialylation similar to the wild type protein, moreover mutant CHO-4 is insensitive to sialidase A treatment, CHO-3 and CHO-4 mtuants are unable to effectively catalyze pro-MMP-2 activation
additional information
-
MMP-14delta279-523, linker and C-terminal hemopexin-like domain deleted, does not undergo rapid autoproteolysis, relatively small differences to wild type
additional information
-
mutant Sol.MT, fails to activate pMMP-2, mutant MTdeltaC, pMMP-2 activation as compared with wild type, neither cell type-dependent nor extracellular matrix component-dependent
additional information
-
partial deletion of the catalytic domain deltacd or the cytoplasmic tail delta577 of MT1-MMP, unable to activate exogenous pro-MMP2, no up-regulation of VEGF expression
additional information
-
specific amino acid substitutions at the Val524-Ile525 site have no effect on shedding of the 50 kDa species, whereas deletion of the entire stem region deltastem-MT1, which lacks Pro509-Gly535, completely abrogates shedding of the 50 kDa species
additional information
-
transcription factor EGR1 gene silencing by siRNA blocks collagen-induced MT1-MMP expression and collagen invasion, integrin signaling through a SRC kinase-dependent pathway is necessary for EGR1 induction, overview
additional information
-
suppression of MMP14 expression in human MCF-7 breast cells blocks MHC class I chain-related molecule A, MICA, shedding, while overexpression of MMP14 enhances it, overview
additional information
-
construction of truncation mutant MT1EADELTATM lacking the pro-peptide and the transmembrane and cytoplasmic domains. Mutant MT1EADELTATM shows different mobility in reducing and non-reducing PAGE compared to the wild-type enzyme, the disulfide bond in the PEX domain is correctly folded, there is no intermolecular disulfide bond formation, and the complex with TIMP-2 is also correctly formed. A PEX-domain-deleted MT1-MMP mutant is no longer able to activate proMMP-2, but retains some proteolytic activity and forms the ternery complex with proMMP-2 and TIMP-2. A MT1-MMP mutant lacking the catalytic domain is catalytically inactive and inhibits the dimerization and complex formation of the enzyme, overview
additional information
deletion of the MT1-MMP cytoplasmic tail or deletion of the hemopexin-like domain
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His-tagged wild-type and mutant Co2+-MT1-MMPs and apoenzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultrafiltration
solubilized recombinant wild-type and mutant enzymes from Escherichia coli strain Rosetta(DE3)pLysS
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
18 kDa inactive fragment ranging from Tyr 112 to Ala 255, 21 kDa fragment ranging from Tyr 122 to Gly 284 and truncated form lacking the cytosolic domain
catalytic and hinge domains of MMP-14 (Tyr112-Ile318), containing an N-terminal methionine and C-terminal hexa-histidines (chMMP-14) expressed as inclusion body in Escherichia coli
-
catalytic domain of MT1-MMP expressed in Escherichia coli, MT1-MMP cDNAs cloned into vector pcDNA3-zeo
-
expressed in COS-7 cells
expression in non-malignant monkey kidney epithelial BS-C-1 and CV-1 cells by co-infecting the cells with the vTF7-3 and vTF-MT1 vaccinia viruses
-
gene MMP14, recombinant coexpression of MMP14 with CCN5 in MCF-7 and CHO-K1 cells
gene MMP14, recombinant expression of C-terminally His-tagged wild-type and mutant Co2+-MT1-MMPs and apoenzymes in Escherichia coli strain BL21(DE3), the plasmid contains the catalytic domain of human MT1-MMP together with the hinge linker to the hemopexin-like domain (residues 112-292). Interaction of the His-tag with the protein cleft, modelling, overview
gene MMP14, recombinant expression of N-terminally HA3-tagged and C-terminally EGFP-tagged wild-type and mutant R111H enzymes in in MRC-5V1 immortalized human fetal lung fibroblasts, in which mutant protein localization is unlikely to be affected by dimerization with endogenous MMP14
gene MMP14, recombinant expression of wild-type enzyme, a soluble enzyme form, and different enzyme MT1-MMP domain constructs in MCF-7 cells, overview
gene MMP14, transient recombinant overexpression of MT1-MMP in HT-1080 cells, quantitative expression analysis
MT1-MMP cDNA subcloned between the HindIII and EcoRI sites of pCDNA3.1 Zeo+ mammalian expression vector, annealed olignucleotides coding for huMT1-MMP signal sequence cloned upstream of ECFP in the NheI-AgeI sites of the pEGFP-C1 vector, amplified residues 283-582 of huMT1-MMP cloned into the BgIII-EcoRI sites of huMT1SSc1 in-frame with EGFP
-
MT1-MMP, lacking the C-terminal transmembrane and cytoplasmic domains, expression in Pichia pastoris
recombinant cdMT1-MMP expressed in Escherichia coli, recombinant deltaTM-MT1-MMP expressed in Pichia pastoris
-
recombinant expression of the truncation mutant MT1EADELTATM in Escherichia coli, expression of the PEX-domain-deleted MT1-MMP mutant
-
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain Rosetta(DE3)pLysS in inclusion bodies
stable expression of FLAG-tagged MT1-MMP in A-431 cells, co-expression with Myc-tagged MT1-MMP
-
the catalytic domain (Tyr112-Val335) is expressed in Escherichia coli BL21 cells
wild-type and various mutants: deletion of catalytic domain, deletion of POX domain, deletion of cytoplasmic tail, deletion of 8, 8 or 12 amino acids at C-terminus, all deletions except catalytic and PEX domain reduced internalization of the protein
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
collagen upregulates both MT1-MMP gene and functions in various cell types
endothelin-1 (ET-1) downregulates matrix metalloproteinase 14 expression in human first trimester trophoblasts via endothelin receptor type B (ETRB). ET-1 downregulates MMP14 mRNA and protein levels. TNF-alpha enhances ET-1-mediated MMP14 downregulation in primary trophoblasts
in patients with tuberculosis, induced sputum enzyme mRNA levels are increased 5.1fold compared with matched controls. Mycobacterium tuberculosis infection of primary human monocytes increases enzyme surface expression 31.7fold and gene expression 24.5fold
interleukin-6 enhances matrix metalloproteinase-14 expression through activator protein-1, AP-1, and via the induced RAF-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2-activator protein-1 pathway, overview
-
MCF-7 cells are transfected with human CCN5 using a polyclonal anti-VTSP antibody detected only full length CCN5. CCN5 cleavage occurs upon coexpression of MMP14 with CCN5 in the MCF-7 cells resulting in the loss of the VTSP epitope in the medium. Cleavage of full-length CCN5 in the CHO-K1-conditioned medium upon addition of recombinant MMP14 or MMP2
MMP-8 is upregulated after stroke in brain in the infarcted tissue compared to healthy control areas, overview
-
Snail increases the expression of membrane type 1-matrix metalloproteinase through activation of ERK-MAPK signaling
-
the enzyme is induced by collagen-gel culture or con-canavalin A treatment
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
dialysis against a 10fold volume of 50 mM Tris-HCl pH 8.5, 100 mM NaCl, 10 mM CaCl2, 10 mM zinc acetate, and 2 M urea
recombinant enzymes from Escherichia coli inclusion bodies by three steps of dialysis in buffer 1 containing 1.5 M urea, 50 mM Tris, pH 8, 150 mM NaCl, 5 mM CaCl2, 0.1 mM ZnCl2, 5 mM 2-mercaptoethanol, 1 mM 2-hydroxyethyl disulphide, 0.1% Brij 35 v/v, and 1 mM PMSF, or in buffer 2 containing 50 mM Tris, pH 8, 150 mM NaCl, 5 mM CaCl2, 0.05 mM ZnCl2, 5 mM 2-mercaptoethanol, 1 mM 2-hydroxyethyl disulphide, 0.1% Brij 35 v/v, and 1 mM PMSF, or in buffer 3 containing 50 mM Tris, pH 8.0, 150 mM NaCl, 5 mM CaCl2, 0.05 mM ZnCl2, 0.1% Brij 35 v/v, and 1 mM PMSF
refolding of the purified polypeptide to active enzyme by gradient dialysis with urea gradient from 6 M decreasing to 0 M and 2-mercaptoethanol gradient from 150 mM decreasing to 0 mM in the presence of CaCl2 and ZnCl2
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
screening, identification, and characterization of affinity peptides, AF7p and Cy5.5-HS7, specific to MT1-MMP and application in tumor imaging, overview. Feasibility of using the subtraction biopanning strategy to screen the affinity peptide targeting MT-loop regions and HS7 is a superior probe for noninvasively imaging MT1-MMP expression in MT1-MMP-positive tumor models. Usage of HS7 in early diagnosis of tumors and in peptide-mediated drugs
diagnostics
-
MMP-14 can be a biomarker in early development of mesothelioma tumours, overview
drug development
medicine
additional information
drug development
-
MMP-14 is an effective therapeutic target in therapy of mesothelioma tumours
drug development
dimeric MT1-MMP inhibitors might be further developed and exploited as an alternative tool to reduce cancer cell invasion
medicine
the understanding of the regulatory mechanisms that control the activity of the key proteinase in tumor cell invasion, is essential for the design of potent and safe anti-cancer therapies
medicine
-
complex reciprocal effects of ERK1/2 and p38 MAPK in the regulation of MT1-MMP activity, which may complicate the use of MAPK-specific inhibitors as therapeutic agents to down-regulate the biologic effects of TGF-beta1 on pericellular collagen degradation and tumor invasion
medicine
-
full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways
medicine
-
MT1-MMP initiates substrate degradation and enhances cell migration, hemopexin-like domain and a nonenzymatic component of the catalytic domain of MT1-MMP are essential for MT1-MMP-mediated cell migration, Rac1 participates in the MT1-MMP signal transduction pathway
medicine
-
MT1-MMP is involved in cell migration and collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation, collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation inhances MT1-MMP activity, hemopexin-like domain of MT1-MMP inhibits collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation and migration
medicine
-
MT1-MMP proteolysis of protective antigen markers makes the MT1-MMP-expressing aggressive invasive cells resistant to the cytotoxic effect of bipartite PA/FP59 toxin, synthetic inhibitors of MMPs are likely to increase the therapeutic anti-cancer effect of anthrax toxin, unique role of furin in the activation of protective antigen markers
medicine
-
some mercaptosulfide inhibitors effectively inhibit activation of proMMP-2 by endogenous MT1-MMP produced by HT1080 human fibrosarcoma cells, block fibronectin degradation by prostate cancer LNCaP cells stably transfected with MT1-MPP
medicine
-
considering the important role of apolipoproteinE for lipid metabolism and atherosclerosis protection, MMP-14 might play an essential role for the development of hyperlipidemia and atherosclerosis as a result of degradation of apolipoprotein E
medicine
-
the relationship between serum MT1-MMP and bone mineral density as well as bone metabolic markers in 206 Chinese postmenopausal women aged 43-80 years is investigated by Western analysis and ELISA. Multiple linear stepwise regression analysis shows that MT1-MMP is not a determinant factor for bone mineral density. Significant positive correlations between MT1-MMP and serum alkaline phosphatase, N-telopeptides of type I collagen are found, and remain significant after adjustment for age and body-mass index. Moreover, serum MT1-MMP, BAP, and NTX decreased in response to alendronate therapy MT1-MMP and bone turnover markers are correlated, and serum MT1-MMP levels may rise with increase in bone turnover
additional information
-
association of MT1-MMP with different membrane subdomains may be crucial in the control of its different activities like cell migration, invasion or MT1-MMP-dependent signaling pathways
additional information
-
degradomics method that efficiently identifies substrates of MMP-14
additional information
glycolysation of MT1-MMP may protect against autolysis and thus stabilize ative MT1-MMP
additional information
-
glycolysation of MT1-MMP may protect against autolysis and thus stabilize ative MT1-MMP
additional information
-
MMP-2 and MT1-MMP are cooperative dynamic components of a cell surface proteolytic axis involved in regulating the cellular signaling environment and pericellular collagen homeostasis
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TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Buttner, F.H.; Hughes, C.E.; Margerie, D.; Lichte, A.; Tschesche, H.; Caterson, B.; Bartnik, E.
Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant aggrecan susbtrate rAgg1murt at the aggrecanase' and the MMP sites. Characterization of MT1-MMP catabolic activities on the interglobular domain of aggrecan
Biochem. J.
333
159-165
1998
Homo sapiens, Homo sapiens (P50281)
Fernandez-Catalan, C.; Bode, W.; Huber, R.; Turk, D.; Calvete, J.J.; Lichte, A.; Tchesche, H.; Maskos, K.
Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor
EMBO J.
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5238-5248
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Homo sapiens
Li, H.; Bauzon, D.E.; Xu, X.; Tschesche, H.; Cao, J.; Sang, Q.A.
Immunological characterization of cell-surface and soluble forms of membrane type 1 matrix metalloproteinase in human breast cancer cells and in fibroblasts
Mol. Carcinog.
22
84-94
1998
Homo sapiens
Annabi, B.; Lachambre, M.P.; Bousquet-Gagnon, N.; Page, M.; Gingras, D.; Beliveau, R.
Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains
Biochem. J.
353
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2001
Homo sapiens (P50281)
Bini, A.; Wu, D.; Schnuer, J.; Kudryk, B.J.
Characterization of stromelysin 1 (MMP-3), matrilysin (MMP-7), and membrane type 1 matrix metalloproteinase (MT1-MMP) derived fibrin(ogen) fragments D-dimer and D-like monomer: NH2-terminal sequences of late-stage digest fragments
Biochemistry
38
13928-13936
1999
Homo sapiens (P50281)
Butler, G.; Butler, M.J.; Atkinson, S.J.; Will, H.; Tamura, T.; van Westrum Steven, S.; Crabbe, T.; Clements, J.; d'Ortho, M.P.; Murphy, G.
The TIMP2 membrane type 1 metalloproteinase "receptor" regulates the concentration and efficient activation of progelatinase A. A kinetic study
J. Biol. Chem.
273
871-880
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Homo sapiens (P50281)
Endo, K.; Takino, T.; Miyamori, H.; Kinsen, H.; Yoshizaki, T.; Furukawa, M.; Sato, H.
Cleavage of syndecan-1 by membrane-type matrix metalloproteinase-1 stimulates cell migration
J. Biol. Chem.
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40764-40770
2003
Homo sapiens (P50281)
Galvez, B.G.; Matias-Roman, S.; Albar, J.P.; Sanchez-Madrid, F.; Arroyo, A.G.
Membrane type 1-matrix metalloproteinase is activated during migration of human endothelial cells and modulates endothelial motility and matrix remodeling
J. Biol. Chem.
276
37491-37500
2001
Homo sapiens (P50281), Homo sapiens
Jiang, A.; Lehti, K.; Wang, X.; Weiss, S.J.; Keski-Oja, J.; Pei, D.
Regulation of membrane-type matrix metalloproteinase 1 activity by dynamin-mediated endocytosis
Proc. Natl. Acad. Sci. USA
98
13693-13698
2001
Homo sapiens (P50281)
Koo, H.M.; Kim, J.H.; Hwang, I.K.; Lee, S.J.; Kim, T.H.; Rhee, K.H.; Lee, S.T.
Refolding of the catalytic and hinge domains of human MT1-MMP expressed in Escherichia coli and its characterization
Mol. Cell
13
118-124
2002
Homo sapiens (P50281), Homo sapiens
Lohi, J.; Lehti, K.; Westermarck, J.; Kahari, V.M.; Keski-Oja, J.
Regulation of membrane-type matrix metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate
Eur. J. Biochem.
239
239-247
1996
Homo sapiens (P50281), Homo sapiens
Luo, X.H.; Liao, E.Y.
Progesterone differentially regulates the membrane-type matrix metalloproteinase-1 (MT1 -MMP) compartment of proMMP-2 activation in MG-63 cells
Horm. Metab. Res.
33
383-388
2001
Homo sapiens (P50281)
Pei, D.; Weiss, S.J.
Transmembrane-deletion mutants of the membrane-type matrix metalloproteinase-1 process progelatinase A and express intrinsic matrix-degrading activity
J. Biol. Chem.
271
9135-9140
1996
Homo sapiens (P50281)
Roderfeld, M.; Buttner, F.H.; Bartnik, E.; Tschesche, H.
Expression of human membrane type 1 matrix metalloproteinase in Pichia pastoris
Protein Expr. Purif.
19
369-374
2000
Homo sapiens (P50281), Homo sapiens
Rozanov, D.V.; Deryugina, E.I.; Ratnikov, B.I.; Monosov, E.Z.; Marchenko, G.N.; Quigley, J.P.; Strongin, A.Y.
Mutation analysis of membrane type-1 matrix metalloproteinase (MT1-MMP). The role of the cytoplasmic tail Cys574, the active site Glu240, and furin cleavage motifs in oligomerization, processing, and self-proteolysis of MT1-MMP expressed in breast carcinoma cells
J. Biol. Chem.
276
25705-25714
2001
Homo sapiens (P50281)
Rozanov, D.V.; Ghebrehiwet, B.; Postnova, T.I.; Eichinger, A.; Deryugina, E.I.; Strongin, A.Y.
The hemopexin-like C-terminal domain of membrane type 1 matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR
J. Biol. Chem.
277
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2002
Homo sapiens (P50281)
Sato, T.; Kondo, T.; Seiki, M.; Ito, A.
Cell type-specific involvement of furin in membrane type 1 matrix metalloproteinase-mediated progelatinase A activation
Ann. N. Y. Acad. Sci.
878
713-715
1999
Oryctolagus cuniculus, Homo sapiens (P50281)
Seiki, M.
Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion
Cancer Lett.
194
1-11
2003
Mus musculus, Homo sapiens (P50281), Homo sapiens
Shofuda, K.I.; Hasenstab, D.; Kenagy, R.D.; Shofuda, T.; Li, Z.Y.; Lieber, A.; Clowes, A.W.
Membrane-type matrix metalloproteinase-1 and -3 activity in primate smooth muscle cells
FASEB J.
15
2010-2012
2001
Rattus norvegicus, Homo sapiens (P50281)
Toth, M.; Hernandez-Barrantes, S.; Osenkowski, P.; Bernardo, M.M.; Gervasi, D.C.; Shimura, Y.; Meroueh, O.; Kotra, L.P.; Galvez, B.G.; Arroyo, A.G.; Mobashery, S.; Fridman, R.
Complex pattern of membrane type 1 matrix metalloproteinase shedding: regulation by autocatalytic cell surface inactivation of active enzyme
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277
26340-26350
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Homo sapiens (P50281)
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Cytoplasmic tail-dependent internalization of membrane-type 1 matrix metalloproteinase is important for its invasion-promoting activity
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155
1345-1356
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Homo sapiens (P50281)
Will, H.; Atkinson, S.J.; Butler, G.S.; Smith, B.; Murphy, G.
The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation. Regulation by TIMP-2 and TIMP-3
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271
17119-17123
1996
Homo sapiens (P50281)
Lee, M.H.; Rapti, M.; Murphy, G.
Unveiling the surface epitopes that render tissue inhibitor of metalloproteinase-1 inactive against membrane type 1-matrix metalloproteinase
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Homo sapiens
Rozanov, D.V.; Strongin, A.Y.
Membrane Type-1 Matrix metalloproteinase functions as a proprotein self-convertase
J. Biol. Chem.
278
8257-8260
2003
Homo sapiens (P50281)
Dong, Z.; Bonfil, R.D.; Chinni, S.; Deng, X.; Trindade Filho, J.C.; Bernardo, M.; Vaishampayan, U.; Che, M.; Sloane, B.F.; Sheng, S.; Fridman, R.; Cher, M.L.
Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue
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166
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Homo sapiens
Hurst, D.R.; Schwartz, M.A.; Ghaffari, M.A.; Jin, Y.; Tschesche, H.; Fields, G.B.; Sang, Q.A.
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377
775-779
2004
Homo sapiens
Toth, M.; Osenkowski, P.; Hesek, D.; Brown, S.; Meroueh, S.; Sakr, W.; Mobashery, S.; Fridman, R.
Cleavage at the stem region releases an active ectodomain of the membrane type 1 matrix metalloproteinase
Biochem. J.
387
497-506
2005
Homo sapiens
Hurst, D.R.; Schwartz, M.A.; Jin, Y.; Ghaffari, M.A.; Kozarekar, P.; Cao, J.; Sang, Q.X.
Inhibition of enzyme activity of and cell-mediated substrate cleavage by membrane type 1 matrix metalloproteinase by newly developed mercaptosulphide inhibitors
Biochem. J.
392
527-536
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Homo sapiens
Minond, D.; Lauer-Fields, J.L.; Nagase, H.; Fields, G.B.
Matrix metalloproteinase triple-helical peptidase activities are differentially regulated by substrate stability
Biochemistry
43
11474-11481
2004
Homo sapiens
Takino, T.; Miyamori, H.; Watanabe, Y.; Yoshioka, K.; Seiki, M.; Sato, H.
Membrane type 1 matrix metalloproteinase regulates collagen-dependent mitogen-activated protein/extracellular signal-related kinase activation and cell migration
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64
1044-1049
2004
Homo sapiens
Rozanov, D.V.; Golubkov, V.S.; Strongin, A.Y.
Membrane type-1 matrix metalloproteinase (MT1-MMP) protects malignant cells from tumoricidal activity of re-engineered anthrax lethal toxin
Int. J. Biochem. Cell Biol.
37
142-154
2005
Homo sapiens
Sounni, N.E.; Roghi, C.; Chabottaux, V.; Janssen, M.; Munaut, C.; Maquoi, E.; Galvez, B.G.; Gilles, C.; Frankenne, F.; Murphy, G.; Foidart, J.M.; Noel, A.
Up-regulation of vascular endothelial growth factor-A by active membrane-type 1 matrix metalloproteinase through activation of Src-tyrosine kinases
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279
13564-13574
2004
Homo sapiens
Cao, J.; Kozarekar, P.; Pavlaki, M.; Chiarelli, C.; Bahou, W.F.; Zucker, S.
Distinct roles for the catalytic and hemopexin domains of membrane type 1-matrix metalloproteinase in substrate degradation and cell migration
J. Biol. Chem.
279
14129-14139
2004
Homo sapiens
Munshi, H.G.; Wu, Y.I.; Mukhopadhyay, S.; Ottaviano, A.J.; Sassano, A.; Koblinski, J.E.; Platanias, L.C.; Stack, M.S.
Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis
J. Biol. Chem.
279
39042-39050
2004
Homo sapiens
Tam, E.M.; Moore, T.R.; Butler, G.S.; Overall, C.M.
Characterization of the distinct collagen binding, helicase and cleavage mechanisms of matrix metalloproteinase 2 and 14 (gelatinase A and MT1-MMP): the differential roles of the MMP hemopexin c domains and the MMP-2 fibronectin type II modules in collage
J. Biol. Chem.
279
43336-43344
2004
Homo sapiens
Wu, Y.I.; Munshi, H.G.; Sen, R.; Snipas, S.J.; Salvesen, G.S.; Fridman, R.; Stack, M.S.
Glycosylation broadens the substrate profile of membrane type 1 matrix metalloproteinase
J. Biol. Chem.
279
8278-8289
2004
Homo sapiens (P50281), Homo sapiens
Mazzone, M.; Baldassarre, M.; Beznoussenko, G.; Giacchetti, G.; Cao, J.; Zucker, S.; Luini, A.; Buccione, R.
Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains
J. Cell Sci.
117
6275-6287
2004
Homo sapiens
Hwang, H.J.; Park, H.J.; Chung, H.J.; Min, H.Y.; Park, E.J.; Hong, J.Y.; Lee, S.K.
Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells
J. Nutr. Biochem.
17
356-362
2006
Homo sapiens
Bai, S.X.; Wang, Y.L.; Qin, L.; Xiao, Z.J.; Herva, R.; Piao, Y.S.
Dynamic expression of matrix metalloproteinases (MMP-2, -9 and -14) and the tissue inhibitors of MMPs (TIMP-1, -2 and -3) at the implantation site during tubal pregnancy
Reproduction
129
103-113
2005
Homo sapiens
Wu, Y.I.; Munshi, H.G.; Snipas, S.J.; Salvesen, G.S.; Fridman, R.; Stack, M.S.
Activation-coupled membrane-type 1 matrix metalloproteinase membrane trafficking
Biochem. J.
407
171-177
2007
Homo sapiens
Lee, H.; Sodek, K.L.; Hwang, Q.; Brown, T.J.; Ringuette, M.; Sodek, J.
Phagocytosis of collagen by fibroblasts and invasive cancer cells is mediated by MT1-MMP
Biochem. Soc. Trans.
35
704-706
2007
Homo sapiens
Kudo, T.; Takino, T.; Miyamori, H.; Thompson, E.W.; Sato, H.
Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels
Cancer Sci.
98
563-568
2007
Homo sapiens
Arroyo, A.G.; Genis, L.; Gonzalo, P.; Matias-Roman, S.; Pollan, A.; Galvez, B.G.
Matrix metalloproteinases: new routes to the use of MT1-MMP as a therapeutic target in angiogenesis-related disease
Curr. Pharm. Des.
13
1787-1802
2007
Homo sapiens
Itoh, Y.
MT1-MMP: a key regulator of cell migration in tissue
IUBMB Life
58
589-596
2006
Homo sapiens
Egawa, N.; Koshikawa, N.; Tomari, T.; Nabeshima, K.; Isobe, T.; Seiki, M.
Membrane type 1 matrix metalloproteinase (MT1-MMP/MMP-14) cleaves and releases a 22-kDa extracellular matrix metalloproteinase inducer (EMMPRIN) fragment from tumor cells
J. Biol. Chem.
281
37576-37585
2006
Homo sapiens
Sithu, S.D.; English, W.R.; Olson, P.; Krubasik, D.; Baker, A.H.; Murphy, G.; D'Souza, S.E.
Membrane-type 1-matrix metalloproteinase regulates intracellular adhesion molecule-1 (ICAM-1)-mediated monocyte transmigration
J. Biol. Chem.
282
25010-25019
2007
Homo sapiens
Currie, J.C.; Fortier, S.; Sina, A.; Galipeau, J.; Cao, J.; Annabi, B.
MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and cell survival
J. Biol. Chem.
282
8142-8149
2007
Homo sapiens
Cao, J.; Chiarelli, C.; Richman, O.; Zarrabi, K.; Kozarekar, P.; Zucker, S.
Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer
J. Biol. Chem.
283
6232-6240
2008
Homo sapiens
Gioia, M.; Monaco, S.; Fasciglione, G.F.; Coletti, A.; Modesti, A.; Marini, S.; Coletta, M.
Characterization of the mechanisms by which gelatinase A, neutrophil collagenase, and membrane-type metalloproteinase MMP-14 recognize collagen I and enzymatically process the two alpha-chains
J. Mol. Biol.
368
1101-1113
2007
Homo sapiens
Lee, H.; Overall, C.M.; McCulloch, C.A.; Sodek, J.
A critical role for the membrane-type 1 matrix metalloproteinase in collagen phagocytosis
Mol. Biol. Cell
17
4812-4826
2006
Homo sapiens
Itoh, Y.; Ito, N.; Nagase, H.; Evans, R.D.; Bird, S.A.; Seiki, M.
Cell surface collagenolysis requires homodimerization of the membrane-bound collagenase MT1-MMP
Mol. Biol. Cell
17
5390-5399
2006
Homo sapiens
Langlois, S.; Nyalendo, C.; Di Tomasso, G.; Labrecque, L.; Roghi, C.; Murphy, G.; Gingras, D.; Beliveau, R.
Membrane-type 1 matrix metalloproteinase stimulates cell migration through epidermal growth factor receptor transactivation
Mol. Cancer Res.
5
569-583
2007
Homo sapiens
Ip, Y.C.; Cheung, S.T.; Fan, S.T.
Atypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma
Mol. Carcinog.
46
225-230
2007
Homo sapiens
Barbolina, M.V.; Stack, M.S.
Membrane type 1-matrix metalloproteinase: substrate diversity in pericellular proteolysis
Semin. Cell Dev. Biol.
19
24-33
2008
Homo sapiens
Barbolina, M.V.; Adley, B.P.; Ariztia, E.V.; Liu, Y.; Stack, M.S.
Microenvironmental regulation of membrane type 1 matrix metalloproteinase activity in ovarian carcinoma cells via collagen-induced EGR1 expression
J. Biol. Chem.
282
4924-4931
2007
Homo sapiens
Prinzen, C.; Truembach, D.; Wurst, W.; Endres, K.; Postina, R.; Fahrenholz, F.
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice
BMC Genomics
10
66
2009
Homo sapiens
Devy, L.; Huang, L.; Naa, L.; Yanamandra, N.; Pieters, H.; Frans, N.; Chang, E.; Tao, Q.; Vanhove, M.; Lejeune, A.; van Gool, R.; Sexton, D.J.; Kuang, G.; Rank, D.; Hogan, S.; Pazmany, C.; Ma, Y.L.; Schoonbroodt, S.; Nixon, A.E.; Ladner, R.C.; Hoet, R.; Henderikx, P.; Tenhoor, C.; Rabbani, S.A.; Valentino, M.
Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis
Cancer Res.
69
1517-1526
2009
Macaca fascicularis, Homo sapiens, Mus musculus, Rattus norvegicus
Park, J.H.; Park, S.M.; Park, S.H.; Cho, K.H.; Lee, S.T.
Cleavage and functional loss of human apolipoprotein E by digestion of matrix metalloproteinase-14
Proteomics
8
2926-2935
2008
Homo sapiens
Sato, H.; Takino, T.
Coordinate action of membrane-type matrix metalloproteinase -1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion
Cancer Sci.
101
843-847
2010
Homo sapiens, Mus musculus
Feng, M.; Cai, X.J.; Zhang, W.; Liu, X.L.; Chen, L.; Zhang, Y.; Zhang, M.X.; Zhang, M.
Interleukin-6 enhances matrix metalloproteinase-14 expression via the RAF-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2-activator protein-1 pathway
Clin. Exp. Pharmacol. Physiol.
37
162-166
2010
Homo sapiens
Sounni, N.E.; Dehne, K.; van Kempen, L.; Egeblad, M.; Affara, N.I.; Cuevas, I.; Wiesen, J.; Junankar, S.; Korets, L.; Lee, J.; Shen, J.; Morrison, C.J.; Overall, C.M.; Krane, S.M.; Werb, Z.; Boudreau, N.; Coussens, L.M.
Stromal regulation of vessel stability by MMP14 and TGFbeta
Dis. Model. Mech.
3
317-332
2010
Homo sapiens, Mus musculus
Laudanski, P.; Swiatecka, J.; Kozlowski, L.; Lesniewska, M.; Wojtukiewicz, M.; Wolczynski, S.
Increased serum level of membrane type 1-matrix metalloproteinase (MT1-MMP/MMP-14) in patients with breast cancer
Folia Histochem. Cytobiol.
48
101-103
2010
Homo sapiens
Niiya, D.; Egawa, N.; Sakamoto, T.; Kikkawa, Y.; Shinkawa, T.; Isobe, T.; Koshikawa, N.; Seiki, M.
Identification and characterization of Lutheran blood group glycoprotein as a new substrate of membrane-type 1 matrix metalloproteinase 1 (MT1-MMP): a systemic whole cell analysis of MT1-MMP-associating proteins in A431 cells
J. Biol. Chem.
284
27360-27369
2009
Homo sapiens
Liu, G.; Atteridge, C.L.; Wang, X.; Lundgren, A.D.; Wu, J.D.
The membrane type matrix metalloproteinase MMP14 mediates constitutive shedding of MHC class I chain-related molecule A independent of A disintegrin and metalloproteinases
J. Immunol.
184
3346-3350
2010
Homo sapiens, Mus musculus
Kaner, R.J.; Santiago, F.; Crystal, R.G.
Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1(+) smokers with early emphysema
J. Leukoc. Biol.
86
913-922
2009
Homo sapiens
Chiu, H.C.; Lu, Y.T.; Chin, Y.T.; Tu, H.P.; Chiang, C.Y.; Gau, C.H.; Nieh, S.; Fu, E.
Cyclosporine A inhibits the expression of membrane type-I matrix metalloproteinase in gingiva
J. Periodontal Res.
44
338-347
2009
Homo sapiens, Rattus norvegicus
Cuadrado, E.; Rosell, A.; Penalba, A.; Slevin, M.; Alvarez-Sabin, J.; Ortega-Aznar, A.; Montaner, J.
Vascular MMP-9/TIMP-2 and neuronal MMP-10 up-regulation in human brain after stroke: a combined laser microdissection and protein array study
J. Proteome Res.
8
3191-3197
2009
Homo sapiens
Crispi, S.; Calogero, R.A.; Santini, M.; Mellone, P.; Vincenzi, B.; Citro, G.; Vicidomini, G.; Fasano, S.; Meccariello, R.; Cobellis, G.; Menegozzo, S.; Pierantoni, R.; Facciolo, F.; Baldi, A.; Menegozzo, M.
Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target
PLoS ONE
4
e7016
2009
Homo sapiens
Itoh, Y.; Takamura, A.; Ito, N.; Maru, Y.; Sato, H.; Suenaga, N.; Aoki, T.; Seiki, M.
Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion
EMBO J.
20
4782-4793
2001
Homo sapiens
Gioia, M.; Fasciglione, G.F.; Monaco, S.; Iundusi, R.; Sbardella, D.; Marini, S.; Tarantino, U.; Coletta, M.
pH dependence of the enzymatic processing of collagen I by MMP-1 (fibroblast collagenase), MMP-2 (gelatinase A), and MMP-14 ectodomain
J. Biol. Inorg. Chem.
15
1219-1232
2010
Homo sapiens
Hawinkels, L.J.; Kuiper, P.; Wiercinska, E.; Verspaget, H.W.; Liu, Z.; Pardali, E.; Sier, C.F.; ten Dijke, P.
Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis
Cancer Res.
70
4141-4150
2010
Homo sapiens
Koshikawa, N.; Mizushima, H.; Minegishi, T.; Iwamoto, R.; Mekada, E.; Seiki, M.
Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor
Cancer Res.
70
6093-6103
2010
Homo sapiens, Mus musculus
Koshikawa, N.; Mizushima, H.; Minegishi, T.; Eguchi, F.; Yotsumoto, F.; Nabeshima, K.; Miyamoto, S.; Mekada, E.; Seiki, M.
Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells
Cancer Sci.
102
111-116
2011
Homo sapiens
Shields, M.A.; Dangi-Garimella, S.; Krantz, S.B.; Bentrem, D.J.; Munshi, H.G.
Pancreatic cancer cells respond to type I collagen by inducing Snail expression to promote membrane type 1 matrix metalloproteinase-dependent collagen invasion
J. Biol. Chem.
286
10495-10504
2011
Homo sapiens
Eisenach, P.A.; Correa de Sampaio, P.; Murphy, G.; Roghi, C.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) ubiquitination at K581 increases cellular invasion through type-I collagen
J. Biol. Chem.
287
11533-11545
2012
Homo sapiens
Nguyen, H.L.; Zucker, S.; Zarrabi, K.; Kadam, P.; Schmidt, C.; Cao, J.
Oxidative stress and prostate cancer progression are elicited by membrane-type 1 matrix metalloproteinase
Mol. Cancer Res.
9
1305-1318
2011
Homo sapiens
Cork, S.M.; Kaur, B.; Devi, N.S.; Cooper, L.; Saltz, J.H.; Sandberg, E.M.; Kaluz, S.; Van Meir, E.G.
A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1
Oncogene
31
5144-5152
2012
Homo sapiens
Ogata, H.; Decaneto, E.; Grossman, M.; Havenith, M.; Sagi, I.; Lubitz, W.; Knipp, M.
Crystallization and preliminary X-ray crystallographic analysis of the catalytic domain of membrane type 1 matrix metalloproteinase
Acta Crystallogr. Sect. F
70
232-235
2014
Homo sapiens (P50281)
Yang, C.; Zhu, L.; Xu, X.; Ning, T.; Ye, J.; Liu, L.
Membrane type 1 matrix metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells
BMC Cancer
13
171
2013
Homo sapiens (P50281), Homo sapiens
Domoto, T.; Takino, T.; Guo, L.; Sato, H.
Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase
Cancer Sci.
103
448-454
2012
Homo sapiens (P50281)
Guo, L.; Takino, T.; Endo, Y.; Domoto, T.; Sato, H.
Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase
J. Biochem.
152
425-432
2012
Homo sapiens (P50281)
Woskowicz, A.M.; Weaver, S.A.; Shitomi, Y.; Ito, N.; Itoh, Y.
MT-LOOP-dependent localization of membrane type I matrix metalloproteinase (MT1-MMP) to the cell adhesion complexes promotes cancer cell invasion
J. Biol. Chem.
288
35126-35137
2013
Homo sapiens (P50281)
Birukawa, N.; Murase, K.; Sato, Y.; Kosaka, A.; Yoneda, A.; Nishita, H.; Fujita, R.; Nishimura, M.; Ninomiya, T.; Kajiwara, K.; Miyazaki, M.; Nakashima, Y.; Ota, S.; Murakami, Y.; Tanaka, Y.; Minomi, K.; Tamura, Y.; Niitsu, Y.
Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth
J. Biol. Chem.
289
20209-20221
2014
Homo sapiens (P50281)
Ma, J.; Tang, X.; Wong, P.; Jacobs, B.; Borden, E.C.; Bedogni, B.
Noncanonical activation of Notch1 protein by membrane type 1 matrix metalloproteinase (MT1-MMP) controls melanoma cell proliferation
J. Biol. Chem.
289
8442-8449
2014
Homo sapiens (P50281)
Tassone, E.; Valacca, C.; Mignatti, P.
Membrane-type 1 matrix metalloproteinase downregulates fibroblast growth factor-2 binding to the cell surface and intracellular signaling
J. Cell. Physiol.
230
366-377
2015
Homo sapiens (P50281)
Sathyamoorthy, T.; Tezera, L.B.; Walker, N.F.; Brilha, S.; Saraiva, L.; Mauri, F.A.; Wilkinson, R.J.; Friedland, J.S.; Elkington, P.T.
Membrane type 1 matrix metalloproteinase regulates monocyte migration and collagen destruction in tuberculosis
J. Immunol.
195
882-889
2015
Homo sapiens (P50281), Homo sapiens
Assent, D.; Bourgot, I.; Hennuy, B.; Geurts, P.; Nol, A.; Foidart, J.; Maquoi, E.
A Membrane-type-1 matrix metalloproteinase (MT1-MMP) - discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells
PLoS ONE
10
e116006
2015
Homo sapiens (P50281), Homo sapiens
Li, X.; Ma, Z.; Wang, H.; Ren, L.; Zhang, D.; Liang, W.; Zhang, G.; Zhang, J.; Yu, D.; Fang, X.
Screening, identification, and characterization of an affinity peptide specific to MT1-MMP and its application in tumor imaging
Bioconjug. Chem.
30
1507-1517
2019
Homo sapiens (P50281)
Cuffaro, D.; Nuti, E.; Gifford, V.; Ito, N.; Camodeca, C.; Tuccinardi, T.; Nencetti, S.; Orlandini, E.; Itoh, Y.; Rossello, A.
Design, synthesis and biological evaluation of bifunctional inhibitors of membrane type 1 matrix metalloproteinase (MT1-MMP)
Bioorg. Med. Chem.
27
196-207
2019
Homo sapiens (P50281)
Decaneto, E.; Suladze, S.; Rosin, C.; Havenith, M.; Lubitz, W.; Winter, R.
Pressure and temperature effects on the activity and structure of the catalytic domain of human MT1-MMP
Biophys. J.
109
2371-2381
2015
Homo sapiens (P50281), Homo sapiens
Pahwa, S.; Bhowmick, M.; Amar, S.; Cao, J.; Strongin, A.Y.; Fridman, R.; Weiss, S.J.; Fields, G.B.
Characterization and regulation of MT1-MMP cell surface-associated activity
Chem. Biol. Drug Des.
93
1251-1264
2019
Homo sapiens (P50281)
de Vos, I.J.; Tao, E.Y.; Ming Ong, S.L.; Goggi, J.L.; Scerri, T.; Wilson, G.R.; Low, C.G.M.; Wong, A.S.W.; Grussu, D.; Stegmann, A.P.A.; van Geel, M.; Janssen, R.; Amor, D.J.; Bahlo, M.; Dunn, N.R.; Carney, T.J.; Lockhart, P.J.; Coull, B.J.; van Steensel, M.A.M.
Functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome phenotype
Hum. Mol. Genet.
27
2775-2788
2018
Homo sapiens (P50281), Homo sapiens, Danio rerio (Q7T2J1), Danio rerio (Q7T2J2), Danio rerio
Majali-Martinez, A.; Velicky, P.; Pollheimer, J.; Knoefler, M.; Yung, H.W.; Burton, G.J.; Tabrizi-Wizsy, N.G.; Lang, U.; Hiden, U.; Desoye, G.; Dieber-Rotheneder, M.
Endothelin-1 down-regulates matrix metalloproteinase 14 and 15 expression in human first trimester trophoblasts via endothelin receptor type B
Hum. Reprod.
32
46-54
2017
Homo sapiens (P50281), Homo sapiens
Fan, L.; Liu, L.; Zhu, C.; Zhu, Q.; Lu, S.; Liu, P.
MT1-MMP inhibits the activity of Bst-2 via their cytoplasmic domains dependent interaction
Int. J. Mol. Sci.
17
818
2016
no activity in Canis familiaris, Homo sapiens (P50281)
Majkowska, I.; Shitomi, Y.; Ito, N.; Gray, N.S.; Itoh, Y.
Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts
J. Biol. Chem.
292
6633-6643
2017
Homo sapiens (P50281), Homo sapiens
Butler, G.S.; Connor, A.R.; Sounni, N. E.; Eckhard, U.; Morrison, C.J.; Noel, A.; Overall, C.M.
Degradomic and yeast 2-hybrid inactive catalytic domain substrate trapping identifies new membrane-type 1 matrix metalloproteinase (MMP14) substrates CCN3 (Nov) and CCN5 (WISP2)
Matrix Biol.
59
23-38
2017
Homo sapiens (P50281)
Decaneto, E.; Vasilevskaya, T.; Kutin, Y.; Ogata, H.; Grossman, M.; Sagi, I.; Havenith, M.; Lubitz, W.; Thiel, W.; Cox, N.
Solvent water interactions within the active site of the membrane type I matrix metalloproteinase
Phys. Chem. Chem. Phys.
19
30316-30331
2017
Homo sapiens (P50281)
Cerofolini, L.; Amar, S.; Lauer, J.L.; Martelli, T.; Fragai, M.; Luchinat, C.; Fields, G.B.
Bilayer membrane modulation of membrane type 1 matrix metalloproteinase (MT1-MMP) structure and proteolytic activity
Sci. Rep.
6
29511
2016
Homo sapiens (P50281)
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