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Information on EC 3.4.24.B4 - matrix metalloproteinase-13 and Organism(s) Rattus norvegicus and UniProt Accession P23097
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3.4.24.B4 matrix metalloproteinase-13Specify your search results
Word Map
- 3.4.24.B4
- cartilage
- chondrocytes
- osteoarthritis
- metalloproteinases
- joint
-
articular
- aggrecan
- degeneration
- mmp-2
- tnf
- knee
- timp-1
- arthritis
- synovial
- interleukin-1
- proteoglycans
-
degener
- cox-2
- osteoblast
- adamts-5
- ligament
-
intra-articular
- collagenases
-
col2a1
- thrombospondin
- pulposus
- runx2
-
cruciate
-
zymography
-
chondrogenic
- gelatinase
- meniscus
-
intervertebral
-
subchondral
-
disintegrin
-
endochondral
-
safranin
- synoviocytes
-
collagenolytic
-
matrix-degrading
-
chondroprotective
-
ossification
-
temporomandibular
- mt1-mmp
-
chondrogenesis
- medicine
- stromelysin-1
- diagnostics
-
cartilage-specific
-
condylar
- analysis
- osteophyte
- drug development
- aggrecanase
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
mmp-13, mmp13, collagenase-3, matrix metalloproteinase-13, matrix metalloproteinase 13, collagenase 3, mmp13a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
MMP-13
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
175449-82-8
-
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
Ac-PLG-[2-mercapto-4-methyl-pentanoyl]-LG-OC2H5 + H2O
?
-
colorimetric substrate
-
-
?
additional information
?
-
-
osteoblastic osteosarcoma cell line UMR 106-01, Ca2+-dependent binding in a two-step mechanism via the required specific 170 kDa enzyme receptor and the required 600 kDa LDL-receptor, internalization and degradation of the enzyme, modeling, the enzyme also binds to mouse fibroblastic cells
-
?
additional information
?
-
-
decrease in types I and III collagen with a concurrent increase in MMP-13 after elastase perfusion in males compared with females, overview
-
-
?
additional information
?
-
-
rat MMP13 is a better gelatinase than a collagenase. Injection of catalytically active recombinant MMP13 enzyme into a rat knee joint to induce cartilage damage
-
-
?
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
additional information
?
-
-
osteoblastic osteosarcoma cell line UMR 106-01, Ca2+-dependent binding in a two-step mechanism via the required specific 170 kDa enzyme receptor and the required 600 kDa LDL-receptor, internalization and degradation of the enzyme, modeling, the enzyme also binds to mouse fibroblastic cells
-
?
additional information
?
-
-
decrease in types I and III collagen with a concurrent increase in MMP-13 after elastase perfusion in males compared with females, overview
-
-
?
additional information
?
-
-
rat MMP13 is a better gelatinase than a collagenase. Injection of catalytically active recombinant MMP13 enzyme into a rat knee joint to induce cartilage damage
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Zn2+
additional information
-
Ca2+-dependent binding to the specific receptor of osteoblastic and fibroblastic cell lines via residue I125
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(4-[[5-(2-ethoxyethyl)-2,4,6-trioxohexahydropyrimidin-5-yl]oxy]phenoxy)-N-(2-fluorobenzyl)benzamide
-
50% inhibition at 01.1 nM, comparison with inhibition of matrix metalloproteinases MMP-2, MMP-8, MMP-12
4-(4-[[5-(2-ethoxyethyl)-2,4,6-trioxohexahydropyrimidin-5-yl]oxy]phenoxy)-N-(3-fluorobenzyl)benzamide
-
50% inhibition at 0.85 nM, comparison with inhibition of matrix metalloproteinases MMP-2, MMP-8, MMP-12
4-(4-[[5-(2-ethoxyethyl)-2,4,6-trioxohexahydropyrimidin-5-yl]oxy]phenoxy)-N-phenylbenzamide
-
50% inhibition at 0.84 nM, comparison with inhibition of matrix metalloproteinases MMP-2, MMP-8, MMP-12
4-(4-[[5-(2-ethoxyethyl)-2,4,6-trioxohexahydropyrimidin-5-yl]oxy]phenoxy)-N-pyridin-3-ylbenzamide
-
50% inhibition at 0.40 nM, comparison with inhibition of matrix metalloproteinases MMP-2, MMP-8, MMP-12
4-[(R)-carboxy-[5-(4'-ethoxyphenyl)-thiophene-2-sulfonylamino]-methyl]-piperidine-1-carboxylic acid iso-propyl ester
-
orally active carboxylic acid-derived MMP-13 inhibitor with subnanomolar potency is identified and tested in a rat intraarticular injection model. Greater than 20000fold in vitro selectivity for MMP-13 over MMP-1 is achieved
N,N'-bis(3-methylbenzyl)pyrimidine-4,6-dicarboxamide
-
a MMP13-specific inhibitor
N2-[(4'-bromobiphenyl-4-yl)sulfonyl]-N-hydroxy-D-valinamide
-
a nonselective inhibitor
additional information
-
orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Two series, quinazolinones and pyrido[3,4-d]pyrimidin-4-ones, that are potent and specific MMP-13 inhibitors, some of which are orally bioavailable. These specific MMP-13 inhibitors, occupying the unique S1'-specificity pocket, do not bind to the Zn2+ ion, effectively preventing cartilage damage in animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats
-
additional information
-
development of MMP-13 inhibitors mechanistically distinct from previously reported broad-spectrum MMP inhibitors with improved selectivity and pharmacokinetics. Chondroprotective effect of MMP-13-selective inhibitors. Effect of MMP-13 inhibition on cartilage degradation in the rat medial meniscal tear model of osteoarthritis, overview
-
additional information
-
MMP-13 activity is not directly inhibited by the imidazo[5,1-c][1,4]thiazine derivative ITZ-1
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state kinetics analysis, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000078
ALS 1-0635
-
pH not specified in the publication, temperature not specified in the publication
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
healthy and elastase-perfused aortas. Increased MMP-13 in experimental abdominal aortic aneurysms in males compared with females, while there are no differences in aortic diameter, collagen, and MMP-13 levels in baseline males versus females, MMP-13 expression analysis, overview
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surfaces under the ruffled borders and some clear zones of osteoclasts. MMP-13 may play an important role in the degradation of type I collagen in bone matrix, acting in concert with cathepsin K and MMP-9 produced by osteoclasts
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upregulation of active MMP-13 in rat brains after 90 min of cerebral ischemia
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from maxillary and mandibular jaws, semi-quantitative RT-PCR analysis, overview
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MMP-13 is mainly produced by neurons, but also by oligodendrocytes
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MMP-13 is mainly produced by neurons, but also by oligodendrocytes
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MMP-13 in perivascular cells may be involved in removal of cartilage matrix proteins such as type II collagen and aggrecan
additional information
-
during experimental gastric ulcer healing induced by acetic acid injection MMP-3 and MMP-3 expression is increased in stromal cells of the gastric mucosa bordering the ulcer. MMP-13 RNAs are confined to the upper layers of the granulation tissue
additional information
-
osteoblastic osteosarcoma cell line UMR 106-01, Ca2+-dependent binding in a two-step mechanism via the required specific enzyme receptor and LDL-receptor-related protein, internalization and degradation of the enzyme, also binding to fibroblastic cells
additional information
-
ibuprofen upregulates expressions of MMP-13 both at mRNA and protein levels
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
gold-labeled MMP-13 is closely associated with collagen fibrils
-
-
MMP-13 activation and its nuclear translocation is an early consequence of an ischemic stimulus
-
hypoxia increases MMP-13 protein secretion from astrocytes
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
additional information
-
lack of transcription-translation coupling on MMP-13 expression in experimental periodontal disease
physiological function
-
MMP-13 is involved in the degradation of extracellular matrix in many kinds of tissues. MMP-13 is an important factor leading to the disorganization of ZO-1, destruction of ZO-1 tight junction protein, and hyperpermeablility of blood-brain barrier in response to hypoxia. Hypoxia-induced MMP-13 expression in astrocytes enhances paracellular permeability of brain endothelial cells
physiological function
-
MMP-13 plays a critical role in parathyroid hormone-induced bone resorption
physiological function
-
tMMP-13 is responsible for cartilage proteoglycan degradation in rat synovial joints
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). MMP13_RAT
466
0
53375
Swiss-Prot
Chloroplast (Reliability: 2)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
generation of a -148 rat MMP-13 promoter construct and a mutation construct of pGL2-MMP-13 promoter by site-directed mutagenesis. MMP-13 knockout by siRNA in UMR106-01 cells
additional information
-
hypoxia-induced MMP-13 overexpression is antagonized by transfection with antisense oligodeoxynucleotides of c-Fos or c-Jun. Transfection of MMP-13-shRNA markedly antagonizes the proteolysis of ZO-1 induced by hypoxic-conditioned medium
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
semi-quantitative RT-PCR expression analysis of MMP-13 in gingiva, lack of transcription-translation coupling on MMP-13 expression in experimental periodontal disease
-
transient expression of a -148 rat MMP-13 promoter construct, subcloned upstream of a CAT reporter gene in pSV0, and of the mutant pGL2-MMP-13 promoter construct in UMR106-01 cells, real time quantitative RT-PCR expression analysis, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HDAC4 represses MMP-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression. HDAC4 interacts with Runx2 on the RD site of the MMP-13 promoter. Binding of HDAC4 to Runx2 is decreased after PTH stimulation
-
hypoxia increases MMP-13 protein and mRNA levels in primary rat astrocyte cultures. c-Fos and c-Jun are involved in hypoxia-induced up-regulation of MMP-13 expression in primary cultured astrocytes
-
ibuprofen upregulates expressions of MMP-13 both at mRNA and protein levels
-
interleukin-1beta induces MMP-13 expression, mediated by extracellular signal-regulated protein kinase, p38 kinase, and c-Jun N-terminal kinase of the MAPK family signal transduction molecules. The interleukin-1beta-induced expression of MMP-13 is selectively inhibited by ERK MAPK pathway inhibitor U0126 and by the imidazo[5,1-c][1,4]thiazine derivative ITZ-1 in vivo, overview
-
MMP-13-shRNA for 24 h significantly inhibits hypoxia-stimulated MMP-13 mRNA expression in cell lysate and enzyme activity in supernatant
-
parathyroid hormone acts via protein kinase A to phosphorylate and stimulate the transactivation of Runx2 for MMP-13 promoter. Runx2 is phosphorylated on Ser28 and Thr340 after 8-bromo cyclic adenosine monophosphate treatment. Runx2 construct having mutations at three phosphorylation sites, S28, S347 and T340, is unable to stimulate MMP-13 promoter activity
-
parathyroid hormone, PTH, stimulation of the MMP-13 promoter in the osteosarcoma cell line UMR-106-01, as well as in primary osteoblastic cells. Trichostatin A, an HDAC inhibitor, markedly stimulated basal transcription from the MMP-13 promoter in UMR 106-01 cells
-
significantly elevated levels of MMP-13 mRNA and protein in case of lipopolysaccharide-induced inflammation throughout 30 days
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
during gastric ulcer healing, enzyme expression as well as matrix metalloproteinase MMP-2 and MMP-3 are induced in stromal cells of the gastric mucosa bordering the ulcer. Enzyme mRNA is confined to the upper layers of the granulation tissue
medicine
-
orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Two series, quinazolinones and pyrido[3,4-d]pyrimidin-4-ones, that are potent and specific MMP-13 inhibitors, some of which are orally bioavailable. These specific MMP-13 inhibitors, occupying the unique S1'-specificity pocket, do not bind to the Zn2+ ion, effectively preventing cartilage damage in animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Bos taurus (O77656), Equus caballus (O18927), Rattus norvegicus (P23097), Xenopus laevis (Q10835)
Barmina, O.Y.; Walling, H.W.; Fiacco, G.J.; Freije, J.M.; Lopez-Otin, C.; Jeffrey, J.J.; Partridge, N.C.
Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization
J. Biol. Chem.
274
30087-30093
1999
Rattus norvegicus
Reiter, L.A.; Freeman-Cook, K.D.; Jones, C.S.; Martinelli, G.J.; Antipas, A.S.; Berliner, M.A.; Datta, K.; Downs, J.T.; Eskra, J.D.; Forman, M.D.; Greer, E.M.; Guzman, R.; Hardink, J.R.; Janat, F.; Keene, N.F.; Laird, E.R.; Liras, J.L.; Lopresti-Morrow, L.L.; Mitchell, P.G.; Pandit, J.; Robertson, D.; Sperger, D.
Potent, selective pyrimidinetrione-based inhibitors of MMP-13
Bioorg. Med. Chem. Lett.
16
5822-5826
2006
Rattus norvegicus
Nakamura, H.; Sato, G.; Hirata, A.; Yamamoto, T.
Immunolocalization of matrix metalloproteinase-13 on bone surface under osteoclasts in rat tibia
Bone
34
48-56
2004
Rattus norvegicus
Calabro, A.; Grappone, C.; Pellegrini, G.; Evangelista, S.; Tramontana, M.; Schuppan, D.; Herbst, H.; Milani, S.
Spatial and temporal pattern of expression of interstitial collagenase, stromelysin/transin, gelatinase A, and TIMP-1 during experimental gastric ulcer healing
Digestion
70
127-138
2004
Rattus norvegicus
Leonardi, R.; Talic, N.F.; Loreto, C.
MMP-13 (collagenase 3) immunolocalisation during initial orthodontic tooth movement in rats
Acta Histochem.
109
215-220
2007
Rattus norvegicus
Cuadrado, E.; Rosell, A.; Borrell-Pages, M.; Garcia-Bonilla, L.; Hernandez-Guillamon, M.; Ortega-Aznar, A.; Montaner, J.
Matrix metalloproteinase-13 is activated and is found in the nucleus of neural cells after cerebral ischemia
J. Cereb. Blood Flow Metab.
29
398-410
2009
Homo sapiens, Rattus norvegicus
Li, J.J.; Nahra, J.; Johnson, A.R.; Bunker, A.; OBrien, P.; Yue, W.S.; Ortwine, D.F.; Man, C.F.; Baragi, V.; Kilgore, K.; Dyer, R.D.; Han, H.K.
Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis
J. Med. Chem.
51
835-841
2008
Rattus norvegicus
Monovich, L.G.; Tommasi, R.A.; Fujimoto, R.A.; Blancuzzi, V.; Clark, K.; Cornell, W.D.; Doti, R.; Doughty, J.; Fang, J.; Farley, D.; Fitt, J.; Ganu, V.; Goldberg, R.; Goldstein, R.; Lavoie, S.; Kulathila, R.; Macchia, W.; Parker, D.T.; Melton, R.; OByrne, E.; Pastor, G.; Pellas, T.; Quadros, E.; Reel, N.
Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13
J. Med. Chem.
52
3523-3538
2009
Homo sapiens, Rattus norvegicus
Tsai, W.C.; Hsu, C.C.; Chang, H.N.; Lin, Y.C.; Lin, M.S.; Pang, J.H.
Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells
J. Orthop. Res.
28
487-491
2010
Rattus norvegicus
Emingil, G.; Afacan, B.; Tervahartiala, T.; Toez, H.; Atilla, G.; Sorsa, T.
GCF and serum myeloperoxidase and matrix metalloproteinase-13 levels in renal transplant patients
Arch. Oral Biol.
55
719-727
2010
Rattus norvegicus
Baragi, V.M.; Becher, G.; Bendele, A.M.; Biesinger, R.; Bluhm, H.; Boer, J.; Deng, H.; Dodd, R.; Essers, M.; Feuerstein, T. et al.
A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models
Arthritis Rheum.
60
2008-2018
2009
Bos taurus, Homo sapiens, Rattus norvegicus
Selvamurugan, N.; Shimizu, E.; Lee, M.; Liu, T.; Li, H.; Partridge, N.C.
Identification and characterization of Runx2 phosphorylation sites involved in matrix metalloproteinase-13 promoter activation
FEBS Lett.
583
1141-1146
2009
Rattus norvegicus
Shimizu, E.; Selvamurugan, N.; Westendorf, J.J.; Olson, E.N.; Partridge, N.C.
HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression
J. Biol. Chem.
285
9616-9626
2010
Mus musculus, Rattus norvegicus
Lu, D.Y.; Yu, W.H.; Yeh, W.L.; Tang, C.H.; Leung, Y.M.; Wong, K.L.; Chen, Y.F.; Lai, C.H.; Fu, W.M.
Hypoxia-induced matrix metalloproteinase-13 expression in astrocytes enhances permeability of brain endothelial cells
J. Cell. Physiol.
220
163-173
2009
Rattus norvegicus
Kimura, H.; Yukitake, H.; Suzuki, H.; Tajima, Y.; Gomaibashi, K.; Morimoto, S.; Funabashi, Y.; Yamada, K.; Takizawa, M.
The chondroprotective agent ITZ-1 inhibits interleukin-1beta-induced matrix metalloproteinase-13 production and suppresses nitric oxide-induced chondrocyte death
J. Pharmacol. Sci.
110
201-211
2009
Homo sapiens, Rattus norvegicus
Li, J.J.; Johnson, A.R.
Selective MMP13 inhibitors
Med. Res. Rev.
31
863-894
2011
Homo sapiens, Mus musculus, Rattus norvegicus
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