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Information on EC 3.4.24.14 - procollagen N-endopeptidase and Organism(s) Mus musculus
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3.4.24.14 procollagen N-endopeptidaseSpecify your search results
Word Map
- 3.4.24.14
- procollagens
- thrombospondin
-
disintegrin
- ehlers-danlos
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dermatosparaxis
- n-propeptide
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c-proteinase
- imperfecta
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aminopropeptide
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pro-alpha
-
disintegrin-like
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adamts-3
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dermatosparactic
-
col5a1
-
hennekam
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Reaction Schemes
Cleaves the N-propeptide of collagen chain alpha1(I) at Pro-/-Gln and of alpha1(II) and alpha2(I) at Ala-/-Gln
Synonyms
adamts2, adamts-2, adamts3, adamts14, procollagen n-proteinase, adamts 3, procollagen i n-proteinase, adam-ts2, aminoprocollagen peptidase, procollagen n-protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAM-TS2
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ADAMTS2
aminoprocollagen peptidase
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aminoterminal procollagen peptidase
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PC I-NP
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pNPI
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procollagen aminopeptidase
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procollagen aminoterminal protease
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Procollagen I N-proteinase
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Procollagen I/II amino-propeptide processing enzyme
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Procollagen N-endopeptidase
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procollagen N-protease
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procollagen N-proteinase
procollagen N-terminal peptidase
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procollagen N-terminal proteinase
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Procollagen peptidase
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type I/II procollagen N-proteinase
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ADAMTS2
i.e. a disintegrin and metalloproteinase with thrombospondin motifs 2
procollagen N-proteinase
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CAS REGISTRY NUMBER
COMMENTARY
68651-94-5
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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
type III procollagen + H2O
?
alpha1 type III, cleavage sites in procollagen from different origins, overview
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-
?
type I procollagen + H2O
?
alpha1 type I, cleavage sites in procollagen from different origins, overview
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-
?
type I procollagen + H2O
?
alpha2 type I, cleavage sites in procollagen from different origins, overview
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-
?
type II procollagen + H2O
?
alpha1 type II, cleavage sites in procollagen from different origins, overview
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-
?
additional information
?
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sequence homology of ADAMTS2 cleavage sites in alpha chain types I-III fibrillar collagens from different species, overview. The murine enzyme ADAMTS2 cleaves at sites 148NFAS-/-QMSY155 in chain alpha1(I), at 178NFAA-/-QMAG185 in chain alpha1(II), and at 151NYSP-/-QFDS158 in chain alpha1(III), as well as at 81NFAA-/-QYSD89 in chains alpha2(I), respectively
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?
additional information
?
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preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution
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?
additional information
?
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sequence homology of ADAMTS2 cleavage sites in type I-III fibrillar collagens from different species, overview
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?
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
?
-
sequence homology of ADAMTS2 cleavage sites in alpha chain types I-III fibrillar collagens from different species, overview. The murine enzyme ADAMTS2 cleaves at sites 148NFAS-/-QMSY155 in chain alpha1(I), at 178NFAA-/-QMAG185 in chain alpha1(II), and at 151NYSP-/-QFDS158 in chain alpha1(III), as well as at 81NFAA-/-QYSD89 in chains alpha2(I), respectively
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?
additional information
?
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preferential substrate specificity of ADAMTS2, 3, and 14 regarding the different fibrillar procollagens is dictated first by their tissue distribution
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
proteolytic cleavage is required for enzyme activation, an autocatalytic cleavage occurring within the carboxy-terminal end, possibly in the PNP-domain, increases its activity
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme requires a neutral to slightly basic pH for activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
the activity of proteinases can be controlled by mechanisms such as clearing by internalization into cells or co-localization with their substrates ADAMTS2, 3 and 14, although being secreted, are immobilized at the cell surface, or very close to it, at a location where procollagen processing is physiologically performed. The ancillary domains, especially the second TSR1, are required for efficient interactions with the cell layer compartment and with extracellular matrix components
evolution
the enzyme belongs to the a disintegrin and metalloproteinase with thrombospondin type I domain proteases (ADAMTS) family, M12B ADAM branch
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
malfunction
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mice with inactivation of both alleles of procollagen N-proteinase (ADAMTS-2) exhibit no difference between knockout mice and their wild type littermates
malfunction
Adamts2-deficient mice phenotype, overview. The absence of ADAMTS2 activity leads to the dermatosparactic type of Ehlers-Danlos syndrome, also previously known as EDS-type VIIC
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
malfunction
mice lacking ADAMTS2 display exacerbate cardiac hypertrophy on pressure overload-induced hypertrophic response, whereas mice with cardiac-specific overexpression of ADAMTS2 display alleviation of this detrimental phenotype. A murine model of aortic banding (AB)-induced cardiac hypertrophy, shows that mice after 4-week AB-treatment exhibit dramatically increased ADAMTS2 protein expression. Loss of ADAMTS2 (ADAMTS2-KO mice) aggravates pressure overload-induced hypertrophy
physiological function
enzyme ADAMTS2 is crucial for fibrillar collagen organization, overview. 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. ADAMTS2 shows potent anti-angiogenic activity
physiological function
ADAMTS2 (a disintegrin and metalloproteinase with thrombospondin motifs 2) is recognized as a metalloproteinase that promotes the cleavage of amino propeptides of types I, II, III, and V procollagens. ADAMTS2 regulates the hypertrophic response through inhibiting the activation of the PI3K/AKT-dependent signaling pathway. ADAMTS2 decreases AKT phosphorylation on hypertrophic stress
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
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). ATS2_MOUSE
1213
0
135299
Swiss-Prot
Secretory Pathway (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
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
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of ADAMTS2-KO mice, phenotype, overview
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Langsjoe, T.K.; Arita, M.; Helminen, H.J.
Cartilage collagen fibril network in newborn transgenic mice analyzed by electron microscopic stereology
Cells Tissues Organs
190
209-218
2009
Mus musculus
Bekhouche, M.; Colige, A.
The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology
Matrix Biol.
44-46C
46-53
2015
Bos taurus (E1BC50), Bos taurus (E1BFV4), Bos taurus (P79331), Canis lupus familiaris (E2R8G2), Gallus gallus, Homo sapiens (O15072), Homo sapiens (O95450), Homo sapiens (Q8WXS8), Mus musculus (Q8C9W3), Ovis aries (W5P0Z2), Rattus norvegicus (D3ZTE7), Sus scrofa (I3LAK9)
Wang, X.; Chen, W.; Zhang, J.; Khan, A.; Li, L.; Huang, F.; Qiu, Z.; Wang, L.; Chen, X.
Critical role of ADAMTS2 (a disintegrin and metalloproteinase with thrombospondin motifs 2) in cardiac hypertrophy induced by pressure overload
Hypertension
69
1060-1069
2017
Homo sapiens (O95450), Homo sapiens, Mus musculus (Q8C9W3), Mus musculus, Rattus norvegicus (P16636)
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