Any feedback?
Literature summary for 3.4.24.14 extracted from
- The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology (2015), Matrix Biol., 44-46, 46-53 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene ADAMTS2, two isozymes from alternative splicing mechanism. Beside the classical 1211 amino acid full length enzyme, a shorter form has been described. It is formed by the first 543 amino acids of the long form (corresponding to exons 1-10) followed by 23 amino acids encoded by an alternative exon present in intron 10 of the long form | Homo sapiens |
| gene ADAMTS2, two isozymes from alternative splicing mechanism. Beside the classical 1211 amino acid full length enzyme, a shorter form has been described. It is formed by the first 543 amino acids of the long form (corresponding to exons 1-10) followed by 23 amino acids encoded by an alternative exon present in intron 10 of the long form | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| extracellular | - |
Homo sapiens | - |
- |
| extracellular | - |
Mus musculus | - |
- |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution | ? | - |
? |  |
| additional information | Mus musculus | preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O15072 | - |
- |
| Homo sapiens | O95450 | - |
- |
| Homo sapiens | Q8WXS8 | - |
- |
| Mus musculus | Q8C9W3 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | ADAMTS2 is synthesized as an inactive proenzyme which is activated by mammalian subtilisins, such as furin, which cleave between the prodomain and the metalloproteinase domain. It has also been shown that an autocatalytic cleavage occurring within the carboxy-terminal end, possibly in the PNP-domain, increases its activity | Homo sapiens |
| proteolytic modification | ADAMTS2 is synthesized as an inactive proenzyme which is activated by mammalian subtilisins, such as furin, which cleave between the prodomain and the metalloproteinase domain. It has also been shown that an autocatalytic cleavage occurring within the carboxy-terminal end, possibly in the PNP-domain, increases its activity | Mus musculus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| aorta | - |
Homo sapiens | - |
| aorta | - |
Mus musculus | - |
| bone | - |
Homo sapiens | - |
| bone | - |
Mus musculus | - |
| cartilage | - |
Homo sapiens | - |
| fibroblast | - |
Homo sapiens | - |
| fibroblast | - |
Mus musculus | - |
| liver | - |
Mus musculus | - |
| macrophage | - |
Homo sapiens | - |
| macrophage | - |
Mus musculus | - |
| mesenchymal cell | - |
Homo sapiens | - |
| mesenchymal cell | - |
Mus musculus | - |
| monocyte | from peripheral blood | Homo sapiens | - |
| monocyte | from peripheral blood | Mus musculus | - |
| additional information | ADAMTS14 is coexpressed with ADAMTS2 in different connective tissues | Homo sapiens | - |
| additional information | ADAMTS2 is mainly expressed by fibroblasts and cells of mesenchymal origin and its expression correlates with the expression of type I and type III collagens. ADAMTS14 is coexpressed with ADAMTS2 in different connective tissues | Homo sapiens | - |
| additional information | ADAMTS2 is mainly expressed by fibroblasts and cells of mesenchymal origin and its expression correlates with the expression of type I and type III collagens. ADAMTS14 is coexpressed with ADAMTS2 in different connective tissues | Mus musculus | - |
| nervous system | - |
Homo sapiens | - |
| skin | - |
Homo sapiens | - |
| skin | - |
Mus musculus | - |
| tendon | - |
Homo sapiens | - |
| tendon | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution | Homo sapiens | ? | - |
? | |
| additional information | preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution | Mus musculus | ? | - |
? | |
| additional information | sequence homology of ADAMTS14 cleavage sites in type I-III fibrillar collagens from different species, overview. ADAMTS14 processes type I procollagen (alpha1 and alpha2 chains) and its strong sequence homology with ADAMTS2 suggests that the cleavage should occur at the same site | Homo sapiens | ? | - |
? | |
| additional information | sequence homology of ADAMTS2 cleavage sites in type I-III fibrillar collagens from different species, overview | Homo sapiens | ? | - |
? | |
| additional information | sequence homology of ADAMTS2 cleavage sites in type I-III fibrillar collagens from different species, overview | Mus musculus | ? | - |
? | |
| additional information | sequence homology of ADAMTS3 cleavage sites in type I-III fibrillar collagens from different species, overview | Homo sapiens | ? | - |
? | |
| type I procollagen + H2O | alpha1 type I, cleavage sites in procollagen from different origins, overview | Homo sapiens | ? | - |
? | |
| type I procollagen + H2O | alpha1 type I, cleavage sites in procollagen from different origins, overview | Mus musculus | ? | - |
? | |
| type I procollagen + H2O | alpha2 type I, cleavage sites in procollagen from different origins, overview | Homo sapiens | ? | - |
? | |
| type I procollagen + H2O | alpha2 type I, cleavage sites in procollagen from different origins, overview | Mus musculus | ? | - |
? | |
| type II procollagen + H2O | alpha1 type II, cleavage sites in procollagen from different origins, overview | Homo sapiens | ? | - |
? | |
| type II procollagen + H2O | alpha1 type II, cleavage sites in procollagen from different origins, overview | Mus musculus | ? | - |
? | |
| type III procollagen + H2O | alpha1 type III, cleavage sites in procollagen from different origins, overview | Homo sapiens | ? | - |
? | |
| type III procollagen + H2O | alpha1 type III, cleavage sites in procollagen from different origins, overview | Mus musculus | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | further to proteolytic processing, the domain composition of ADAMTS2 can also result from an alternative splicing mechanism. Beside the classical 1211 amino acid full length enzyme, a shorter form has been described. It is formed by the first 543 amino acids of the long form (corresponding to exons 1-10) followed by 23 amino acids encoded by an alternative exon present in intron 10 of the long form. This truncated form does contain the metalloproteinase domain but does not show any significant aminoprocollagen peptidase activity | Homo sapiens |
| More | further to proteolytic processing, the domain composition of ADAMTS2 can also result from an alternative splicing mechanism. Beside the classical 1211 amino acid full length enzyme, a shorter form has been described. It is formed by the first 543 amino acids of the long form (corresponding to exons 1-10) followed by 23 amino acids encoded by an alternative exon present in intron 10 of the long form. This truncated form does contain the metalloproteinase domain but does not show any significant aminoprocollagen peptidase activity | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ADAMTS14 | - |
Homo sapiens |
| ADAMTS2 | - |
Homo sapiens |
| ADAMTS2 | - |
Mus musculus |
| ADAMTS3 | - |
Homo sapiens |
| aminoprocollagen endopeptidase | - |
Homo sapiens |
| aminoprocollagen endopeptidase | - |
Mus musculus |
| procollagen N-proteinase | - |
Homo sapiens |
| procollagen N-proteinase | - |
Mus musculus |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | enzyme synthesis is increased by TGF beta in vitro and in fibrotic lesions in vivo. ADAMTS2 overexpression by macrophages and peripheral blood monocytes is stimulated by glucocorticoids | up |
| Mus musculus | enzyme synthesis is increased by TGF beta in vitro and in fibrotic lesions in vivo. ADAMTS2 overexpression by macrophages and peripheral blood monocytes is stimulated by glucocorticoids | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the procollagen N-propeptidase belongs to the 'a disintegrin and metalloproteinase with thrombospondin type I domain' proteases (ADAMTS) family, M12B ADAM branch. Beside their specific enzymatic activity, the members are characterized by the presence of four thrombospondin type I domains (TSR1) and a C-terminal procollagen N-proteinase (PNP) domain comprising a protease-and-lacunin (PLAC) domain | Homo sapiens |
| evolution | the procollagen N-propeptidase belongs to the 'a disintegrin and metalloproteinase with thrombospondin type I domain' proteases (ADAMTS) family, M12B ADAM branch. Beside their specific enzymatic activity, the members are characterized by the presence of four thrombospondin type I domains (TSR1) and a C-terminal procollagen N-proteinase (PNP) domain comprising a protease-and-lacunin (PLAC) domain. ADAMTS14 is coexpressed with ADAMTS2 | Homo sapiens |
| evolution | the procollagen N-propeptidase belongs to the 'a disintegrin and metalloproteinase with thrombospondin type I domain' proteases (ADAMTS) family, M12B ADAM branch. Beside their specific enzymatic activity, the members are characterized by the presence of four thrombospondin type I domains (TSR1) and a C-terminal procollagen N-proteinase (PNP) domain comprising a protease-and-lacunin (PLAC) domain. ADAMTS14 is coexpressed with ADAMTS2 | Mus musculus |
| malfunction | in Adamts2-KO mouse livers, collagen fibers are thinner and more irregular than in the control littermates, which correlated also with faster collagen degradation. Fragility of the skin occurs in Adamts2-KO mice | Mus musculus |
| malfunction | in vivo, the formation of tumors in nude mice by HEK cells is strongly reduced when they overexpress ADAMTS2, an observation that is correlated to a reduced intratumoral vascularization but that might also involve direct anti-tumor effects. The absence of ADAMTS2 activity leads to a different type of disease, the dermatosparactic type of Ehlers-Danlos syndrome (EDS, also previously known as EDS-type VIIC). The main clinical manifestation of this rare genetic disease is the fragility of the skin, as in Adamts2-KO mice, but joint laxity is usually only moderate, which contrasts with the hypermobility in arthrochalasic EDS. The arthrochalasic type of EDS, caused by mutations affecting the aminoprocollagen cleavage site in alpha1 or alpha2 type I procollagen, is mainly characterized by joint hyperlaxity while skin collagen fibers are only moderately affected. EDS phenotypes, overview | Homo sapiens |
| physiological function | ADAMTS2 and ADAMTS3, but not ADAMTS14, are more abundant in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Their expression overlap the area positive for CD31 or CD68 suggesting their expression by endothelial cells or macrophages. The Adamts14 gene is potentially implicated in knee osteoarthritis in woman | Homo sapiens |
| physiological function | ADAMTS2 induces the apoptosis of endothelial cells by a mechanism independent of its catalytic activity but potentially related to interactions with a cell surface receptor by one of its C-terminal domains. The role of ADAMTS2 is crucial for collagen fibrils formation | Mus musculus |
| physiological function | ADAMTS2 induces the apoptosis of endothelial cells by a mechanism independent of its catalytic activity but potentially related to interactions with a cell surface receptor by one of its C-terminal domains. The role of ADAMTS2 is crucial for collagen fibrils formation. ADAMTS2 and ADAMTS3, but not ADAMTS14, are more abundant in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Their expression overlap the area positive for CD31 or CD68 suggesting their expression by endothelial cells or macrophages | Homo sapiens |
| physiological function | ADAMTS3 promotes the release of a proteolytically cleaved active form of VEGF-C, a process that increases VEGF-R3 signaling. ADAMTS2 and ADAMTS3, but not ADAMTS14, are more abundant in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Their expression overlap the area positive for CD31 or CD68 suggesting their expression by endothelial cells or macrophages | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
