Information on EC 3.4.24.22 - stromelysin 2

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY hide
3.4.24.22
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RECOMMENDED NAME
GeneOntology No.
stromelysin 2
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Similar to stromelysin 1, but action on collagen types III, IV and V is weak
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY hide
140610-48-6
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Mus musculus BALB/c
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UniProt
Manually annotated by BRENDA team
Mus musculus C57BL/6
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UniProt
Manually annotated by BRENDA team
K5-IkBa mice
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
despite their similar substrate specificities, the stromelysins show differential patterns of transcriptional regulation and tissue distribution that hint at distinct physiological functions in processes such as skeletal development, wound healing, and vascular remodeling
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(7-Methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Val-Glu-norvaline-Trp-Arg-Lys(2,4-dinitrophenyl)-NH2 + H2O
(7-Methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Val-Glu + norvaline-Trp-Arg-Lys(2,4-dinitrophenyl)-NH2
show the reaction diagram
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Ac-Pro-Leu-Gly-(2-mercapto-4-methyl-pentanoyl)-Leu-Gly-OC2H5 + H2O
?
show the reaction diagram
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-
-
?
ADAMTS-like protein 1 + H2O
?
show the reaction diagram
Aggrecan core protein + H2O
?
show the reaction diagram
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Azocoll + H2O
?
show the reaction diagram
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Cartilage link protein + H2O
?
show the reaction diagram
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cleaved at His16-Ile17 bond
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casein + H2O
?
show the reaction diagram
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Collagen + H2O
?
show the reaction diagram
collagen alpha-1(l) + H2O
?
show the reaction diagram
collagen alpha-2(I) + H2O
?
show the reaction diagram
collagen alpha-2(v) + H2O
?
show the reaction diagram
cleavage site is GPHG487-/-488IQGP
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?
Elastin + H2O
?
show the reaction diagram
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Fibronectin + H2O
?
show the reaction diagram
Gelatin + H2O
?
show the reaction diagram
lysyl oxidase + H2O
?
show the reaction diagram
platelet-derived growth factor receptor alpha + H2O
?
show the reaction diagram
cleavage into two fragments of about 40 and 80 kDa, cleavage site is VPAS416.417ILDL in the extracellular domain
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?
procollagenase + H2O
?
show the reaction diagram
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?
proMMP-1 + H2O
MMP-1 + propeptide
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADAMTS-like protein 1 + H2O
?
show the reaction diagram
Fibronectin + H2O
?
show the reaction diagram
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-
?
procollagenase + H2O
?
show the reaction diagram
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
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zinc metalloenzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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GM6001
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a broad-spectrum MMP inhibitor
N-isobutyl-N-(4-methoxy-phenylsulfonyl)glycyl hydroxamic acid
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i.e. NNGH, study of binding mode. Interaction of inhibitor with Zn1 atom and S1’ subsite
PAI-1
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functions as an upstream regulator of a MMP-10-initiated collagenolytic phenotype, it blocks conversion of MMP-10 to its active form. Neutralization of endogenous PAI-1 with function blocking antibodies accelerates both collagenolysis and activation of MMP-10
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Specific tissue inhibitor of metalloproteinases
TIMP-1
TIMP-2
tissue inhibitor of metalloproteinases 1
TIMP-1, the protein is expressed in HEK 293E cells, enzyme binding structure analysis and mechanism of inhibition, detailed overview and comparison to stromelysin-1, EC 3.4.24.17
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tissue inhibitor of metalloproteinases 2
additional information
the endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs. Identification of a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
purified proMMP-10-catalytic domain is activated overnight in the presence of the organomercurial compound 4-aminophenyl mercuric acetate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.023
(7-Methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Val-Glu-norvaline-Trp-Arg-Lys(2,4-dinitrophenyl)-NH2
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additional information
additional information
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enzyme cleavage site specificity and kinetics, overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.8
(7-Methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Val-Glu-norvaline-Trp-Arg-Lys(2,4-dinitrophenyl)-NH2
Homo sapiens
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000011
tissue inhibitor of metalloproteinases 1
catalytic enzyme domain, pH 7.0, 37°C
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0.0000058
tissue inhibitor of metalloproteinases 2
catalytic enzyme domain, pH 7.0, 37°C
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additional information
additional information
inhibition kinetics using the isolated enzyme's catalytic domain, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
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activity against aggrecan at pH 5.5 is double that at pH 6.0
7.5 - 8
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azocoll
7.5
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
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6.0: 25% of activity maximum, 7.5-8.0: activity maximum, azocoll
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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lymphoma cell, expression of enzyme is induced upon contact of cell with endothelial cells
Manually annotated by BRENDA team
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lymphoma cell, expression of enzyme is induced upon contact of cell with endothelial cells. Enzyme expression is also induced following exposure to interleukins IL-4, IL-6, and IL-13, but not IL-1
Manually annotated by BRENDA team
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subcutaneous and gonadal adipose tissue
Manually annotated by BRENDA team
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MMP-10 is notably increased in neurons of the ischemic brain but not in healthy areas
Manually annotated by BRENDA team
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induction of enzyme expression by TNF-alpha and EGF
Manually annotated by BRENDA team
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SV40-transformed
Manually annotated by BRENDA team
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colon adenocarcinoma cell line
Manually annotated by BRENDA team
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proenzyme expression is markedly induced in endothelial cells undergoing capillary tube morphogenesis. Enzyme-induced activation of matrix metalloproteinase MMP-1 correlates with tube regression and gel contraction
Manually annotated by BRENDA team
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expression of matrix metalloproteinases MMP-1, MMP-7 and MMP-10 by migrating enterocytes bordering intestinal ulcers
Manually annotated by BRENDA team
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transformed embryo cell line, can be induced by a tumor promoter
Manually annotated by BRENDA team
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keratinocyte cell line, induction of enzyme and matrix metalloproteinases MMP-1 and MMP-3 by UVA, induction is suppressed by beta-carotene. beta-Carotene dose-dependently quenches 1O2-mediated induction of enzyme and MMP-1
Manually annotated by BRENDA team
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MMP-10 and MMP-1 are up-regulated in HaCaT II-4 cells
Manually annotated by BRENDA team
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colon adenocarcinoma cell line
Manually annotated by BRENDA team
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MMP-10 protein levels are higher in the tumor tissues than in the adjacent normal tissues
Manually annotated by BRENDA team
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postmortem or following surgery
Manually annotated by BRENDA team
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no differences in MMP-10 in the plasma of hypertensive versus normotensive subjects
Manually annotated by BRENDA team
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at all ages in normal and acanthotic skin
Manually annotated by BRENDA team
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colon adenocarcinoma cell line
Manually annotated by BRENDA team
HUVEC, quantitative RT-PCR of MMPs, overview
Manually annotated by BRENDA team
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induction of enzyme expression by TNF-alpha and EGF
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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synthesized as preproenzyme of 476 amino acids and secreted from cells as the proenzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 56000, pro-MMP-10, SDS-PAGE, x * 42000, mature MMP-10, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
additional information
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potential glycosylation site at Asn100, but is unlikely to be a glycoprotein as it does not bind concanavalin A
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified active human MMP-10 catalytic domain in complex with inhibitor protein TIMP-2, hanging drop vapor diffusion method, mixing of proteins in a 1:1.1 (mol/mol) ratio, 4.5-5.5 mg/ml protein in 20 mM Tris, pH 8.5 and 150 mM NaCl, are mixed with reservoir solution containing 0.1 M HEPES, pH 7.5, and 25% w/v PEG 2000 monomethyl ether, 1-2 weeks, X-ray diffraction structure determination and analysis at 2.1 A resolution, molecular replacement, comparison and analysis of the crystal structure of the human MMP-10/TIMP-1 complex, PDB ID 3V96
purified isolated catalytic enzyme domain in complex with inhibitor TIMP1, 1:1.2 (mol/mol) mixture of enzyme protein and fully deglycosylated TIMP-N30A mutant is concentrated to achieve a final protein concentration of 4-5 mg/ml. Crystals are grown by hanging drop vapor diffusion method at room temperature in 0.1 M sodium dihydrogen phosphate, pH 6.5, 12% w/v PEG 8000, 2 weeks, X-ray diffraction structure determination and analysis at 1.9 A resolution, molecular replacement
recombinant catalytic domain, in complex with inhibitor N-isobutyl-N-(4-methoxy-phenylsulfonyl)glycyl hydroxamic acid, i.e. NNGH. Comparison with structure of matrix metalloproteinase MMP-3
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, prostromelysin 2, 50 mM Tris-HCl, pH 7.5, 0.15 M NaCl, 10 mM CaCl2, 0.02% w/v NaN3, 0.05% Brij 35, stable for 4 weeks
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4°C, prostromelysin 2, 50 mM Tris-HCl, pH 7.5, 0.15 M NaCl, 10 mM CaCl2, 0.02% w/v NaN3, 0.05% Brij 35, stable for 2 weeks
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme MMP-10 catalytic domain from Escherichia coli strain BL21 (DE3), by anion exchange chromatography and gel filtration
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression analysis
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expression analysis of MMP10 in cancerous and healthy oral tissues, overview
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expression of the enzyme catalytic domain in Escherichia coli strain BL21 (DE3)
gene MMP-10, semi-quantitative RT-PCR expression analysis
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MMP-10 DNA and amino acid sequence determination and expression analysis in HUVECs, transcriptional regulation of MMP-10 by Ets transcription factors, overview
transin and transin-2 genes have very similar structures. The most striking difference is the much larger size of the intron separating exons 6 and 7 of the transin gene compared to the size of the corresponding intron in the transin-2 gene
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enhanced collagen degradation, in case of epithelial-to-mesenchymal transition stimulated by transforming growth factor-beta as well as epidermal growth factor receptor, is coupled to a significant increase in matrix metalloproteinase MMP-10 expression and is involved a proteolytic axis composed of plasmin, MMP-10, and MMP-1, ec 3.4.24.7
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high expression of MMP-10 is frequently observed and is significantly correlated with the invasiveness and metastasis in head and neck squamous cell carcinoma cases
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increased MMP-10 levels in severe sepsis
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loss or knockdown of transcription factor CHF1/Hey2 in vascular smooth muscle cells leads to increased expression and activity of MMP10 at baseline. CHF1/Hey2 regulates MMP10 expression through multiple E boxes
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MMP-10 expression is downregulated with age, overview
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Mmp10 is overexpressed in lung tumors induced by either the smoke carcinogen urethane or oncogenic Kras
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neuronal MMP-10 is upregulated after stroke in brain in the infarcted tissue compared to healthy control areas, overview
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PD98059 and SP600125, ERK and JNK inhibitors, respectively, repress VEGF-induced MMP-10 expression to mRNA expression levels lower than the basal expression of MMP-10
stromelysin-2 is slightly downregulated in obese adipose tissue compared to non-obese adipose tissue
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strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types
VEGF165 induces MMP-10 expression about 2fold. LY294002 inhibits VEGF-induced MMP-10 expression, indicating the involvement of PI3K in VEGF-induced MMP-10 expression
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
down
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aldose reductase inhibitor, fidarestat, normalizes high-glucose level-mediated suppression of MMP-10 expression, it downregulates MMP-10 expression
medicine
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cells resistant to protein kinase C potentiated, transcription factor p53 mediated apoptosis express a higher level of matrix metalloproteinases MMP-9 and MMP-10. Matrix metalloproteinases function confers protection from protein kinase C/p53 induced apoptosis and are implicated in tumor cell resistance
up
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a high glucose level decreases MMP-10 expression in corneal epithelial cells
V94G
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constitutively active mutant, mice expressing the mutant in keratinocytes have no alterations in skin architecture, and the healing rate of skin wounds is normal. Histologically, deposition of new matrix is reduced and keratinocytes at the migrating epidermal tip are scattered, the staining pattern of laminin-5 at the wound site is altered
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine