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Literature summary for 3.4.24.B4 extracted from
- The structure, regulation, and function of human matrix metalloproteinase-13 (2002), Crit. Rev. Biochem. Mol. Biol., 37, 149-166.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 12-O-tetradecanoyl phorbol 13-acetate | 8fold activation of transcriptional activity in chondrocytes | Homo sapiens |  |
| hepatocyte growth factor | stimulation of enzyme expression in osteoarthritic chondrocytes | Homo sapiens | |
| integrins | e.g. integrin alpha1beta and alpha2beta1, induction via MAPkinase | Homo sapiens | |
| interleukin-1 | alpha and beta form, induction of enzyme expression, which is inhibited by 15-deoxy-DELTA12,14-prostaglandin J2, induction of enzyme expression in chondrosarcoma cells requires nuclear factor-kappaB nuclear translocation, p38 MAPkinase activity, c-Jun N-terminal kinase activity | Homo sapiens | |
| oncostatin | induction of enzyme expression, requires phosphorylation of JAK3 | Homo sapiens | |
| stromelysin-1 | concentration-dependent activation by cleavage of the proform | Homo sapiens | |
| transforming growth factor-beta1 | strong induction of enzyme expression in KMST fibroblasts, increase of enzyme expression by inhibition of p38 mitose-activated protein kinase | Homo sapiens | |
| Tumor necrosis factor alpha | induction of enzyme expression, which is inhibited by 15-deoxy-DELTA12,14-prostaglandin J2 | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | truncated enzyme form comprising the amino acid residues 249-451 shows no triple helicase activity against collagen type I and II | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| bone morphogenetic protein 2 | down-regulation of enzyme expression in osteoblasts, can be overcome by noggin | Homo sapiens | |
| bone morphogenetic protein 4 | down-regulation of enzyme expression in osteoblasts, can be overcome by noggin | Homo sapiens | |
| bone morphogenetic protein 6 | down-regulation of enzyme expression in osteoblasts, can be overcome by noggin | Homo sapiens | |
| furin | inhibition of enzyme induction by TGFbeta1 in chondrocytes | Homo sapiens | |
| mannose-6-phosphate/insulin-like growth factor 2 receptor | inhibition of enzyme induction by TGFbeta1 in chondrocytes | Homo sapiens | |
| P53 | down-regulation of enzyme expression, possibly contributes to the dysregulation of the enzyme observed in cancer | Homo sapiens | |
| tissue matrix metalloproteinase inhibitor-1 | in a ratio of enzyme to inhibitor of 1:1 | Homo sapiens | |
| tissue matrix metalloproteinase inhibitor-2 | in a ratio of enzyme to inhibitor of 1:1 | Homo sapiens | |
| tissue matrix metalloproteinase inhibitor-3 | fast inhibition, in a ratio of enzyme to inhibitor of 1:1 | Homo sapiens | |
| transforming growth factor-beta1 | i.e. TGFbeta1, accelerates the decay of the enzymes mRNA and decreased enzyme expression in osteoblasts | Homo sapiens |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | zinc binding motif at the catalytic site | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| fibrillin-1 + H2O | Homo sapiens | enzyme affects microfibril organization and integrity, leadint ot loss of normal microfibril function | ? | - |
? | |
| fibrillin-2 + H2O | Homo sapiens | enzyme affects microfibril organization and integrity, leadint ot loss of normal microfibril function | ? | - |
? | |
| interstitial collagen type I + H2O | Homo sapiens | fibrillar collagen | ? | - |
? | |
| interstitial collagen type II + H2O | Homo sapiens | fibrillar collagen, best substrate, cleavage sites are Gly906-Leu907, Gly909-Gln910, and Gly912-Ile913 | ? | - |
? | |
| interstitial collagen type III + H2O | Homo sapiens | fibrillar collagen | ? | - |
? | |
| additional information | Homo sapiens | enzyme expression is limited to situations of rapid extracellular matrix remodeling, transcriptional regulatory mechansim, strict regulation of expression | ? | - |
? | |
| protein + H2O | Homo sapiens | enzyme plays a key role in the matrix metalloproteinase activation cascade, and in tumor invasion and metastasis, and appears to be critical in bone metabolism and homeostasis | peptides | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | stromelysin-1 can activate the enzyme by cleavage of the Glu57-Leu58 bond of the proform resulting in formation of an intermediate of 50 kDa which is further processed to the 48 kDa active mature form, inactive proform can be activated in 3 different ways: 1. autoproteolytically, 2. via cleavage by several other matrix metalloproteases, 3. in a three-step process using aminophenylmercuric acetate | Homo sapiens |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| proteolytic degradation of proteins | preference for cleavage at Gly- or -Leu | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| bone | enzyme is expressed during both intramembranous ossification in skull and endochondral ossification in long bones during gestation | Homo sapiens | - |
| breast carcinoma cell | - |
Homo sapiens | - |
| cervical carcinoma cell | - |
Homo sapiens | - |
| chondrocyte | osteoarthritic and non-osteoarthritic | Homo sapiens | - |
| chondrosarcoma cell | - |
Homo sapiens | - |
| fibroblast | - |
Homo sapiens | - |
| KMST-6 cell | - |
Homo sapiens | - |
| melanoma cell | - |
Homo sapiens | - |
| additional information | no expression by isolated synovial fibroblasts | Homo sapiens | - |
| osteoblast | - |
Homo sapiens | - |
| skin cancer cell | melanoma and non-melanoma skin cancer | Homo sapiens | - |
| squamous cell carcinoma cell | enzyme expression is related to tumor aggresiveness | Homo sapiens | - |
| stromal cell | adjacent to breast tumor cancer cells | Homo sapiens | - |
| SW-1353 cell | chondrosarcoma cell line | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2,4-dinitrophenyl-GPLGMRSGL-NH2 + H2O | - |
Homo sapiens | 2,4-dinitrophenyl-GPLGM + RSGL-NH2 | - |
? | |
| aggrecan + H2O | cleavage site in the interglobular domain is PEN341-FFG | Homo sapiens | ? | - |
? | |
| alpha2-antichymotrypsin + H2O | degradation, cleavage site is Ala362-Leu363 | Homo sapiens | ? | - |
? | |
| collagen type IV chain alpha1 + H2O | fibrillar collagen, wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| collagen type IV chain alpha2 + H2O | fibrillar collagen, wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| collagen type IX + H2O | fibrillar collagen, wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| collagen type X + H2O | fibrillar collagen, wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| collagen type XIV + H2O | fibrillar collagen, wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| factor XII + H2O | cleavage site is Gly376-Leu377 | Homo sapiens | ? | - |
? | |
| fibrillin-1 + H2O | - |
Homo sapiens | ? | - |
? | |
| fibrillin-1 + H2O | enzyme affects microfibril organization and integrity, leadint ot loss of normal microfibril function | Homo sapiens | ? | - |
? | |
| fibrillin-2 + H2O | - |
Homo sapiens | ? | - |
? | |
| fibrillin-2 + H2O | enzyme affects microfibril organization and integrity, leadint ot loss of normal microfibril function | Homo sapiens | ? | - |
? | |
| fibrinogen alpha chain + H2O | - |
Homo sapiens | ? | - |
? | |
| Fibronectin + H2O | - |
Homo sapiens | ? | - |
? | |
| Gelatin + H2O | - |
Homo sapiens | ? | - |
? | |
| interstitial collagen type I + H2O | fibrillar collagen | Homo sapiens | ? | - |
? | |
| interstitial collagen type II + H2O | fibrillar collagen, best substrate, cleavage sites are Gly906-Leu907, Gly909-Gln910, and Gly912-Ile913 | Homo sapiens | ? | - |
? | |
| interstitial collagen type III + H2O | fibrillar collagen | Homo sapiens | ? | - |
? | |
| large tenascin C isoform + H2O | no activity with the small isoform | Homo sapiens | ? | - |
? | |
| additional information | collagen type XI is not cleaved by wild-type enzyme and truncated mutant | Homo sapiens | ? | - |
? | |
| additional information | enzyme expression is limited to situations of rapid extracellular matrix remodeling, transcriptional regulatory mechansim, strict regulation of expression | Homo sapiens | ? | - |
? | |
| perlecan + H2O | - |
Homo sapiens | ? | - |
? | |
| plasminogen activator inhibitor + H2O | degradation | Homo sapiens | ? | - |
? | |
| protein + H2O | - |
Homo sapiens | peptides | - |
? | |
| protein + H2O | enzyme plays a key role in the matrix metalloproteinase activation cascade, and in tumor invasion and metastasis, and appears to be critical in bone metabolism and homeostasis | Homo sapiens | peptides | - |
? | |
| transforming growth factor-beta1 + H2O | - |
Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | enzyme domain structure, overview | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| M10.013 | Merops-ID | Homo sapiens |
| matrix metalloproteinase-13 | - |
Homo sapiens |
| MMP-13 | - |
Homo sapiens |
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