Any feedback?
Information on EC 3.4.24.B11 - ADAMTS1 endopeptidase and Organism(s) Mus musculus and UniProt Accession P97857
for references in articles please use BRENDA:EC3.4.24.B11preliminary BRENDA-supplied EC number
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.24.B11 ADAMTS1 endopeptidaseSpecify your search results
Word Map
- 3.4.24.B11
- endothelial
-
antiangiogenic
- vessel
- metastasis
-
angiogenic
- endostatin
- vein
-
umbilical
- neovascularization
- huvecs
-
microvessels
- collagen
-
bevacizumab
-
nude
-
anti-angiogenesis
- thrombospondin-1
-
chorioallantoic
- colorectal
-
disintegrin
- capillary
-
brain-specific
-
microvascular
- plasminogen
-
vasculature
- metalloproteinases
- matrigel
-
progression-free
- angiostatin
-
vegf-induced
- fumagillin
- bfgf
- adamts4
-
avastin
-
angiogenesis-related
-
epithelium-derived
-
proangiogenic
- xviii
-
angiogenesis-dependent
- medicine
-
anti-vascular
- sorafenib
- sunitinib
- versican
- adam17
-
kringle
-
capillary-like
-
vegf-stimulated
- aggrecanase
- vegfr-2
- pazopanib
-
anti-vegf
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Tetrapoda
The expected taxonomic range for this enzyme is: Tetrapoda
Synonyms
angiogenesis inhibitor, adamts1, adam metallopeptidase, meth-1, meth1, xadamts1, adam-ts1, xenopus ortholog of adamts1, adam-metallopeptidase with thrombospondin type 1 motifs-1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAMTS-1
a disintegrin and metalloproteinase with thrombospondin motifs-1
a disintegrin and metalloproteinase with thrombospondin motifs 1
-
-
ADAMTS-1
ADAMTS1
ADAMTS-1
-
a matrix metalloproteinase with disintegrin and thrombospondin motifs
ADAMTS-1
-
disintegrin-like and metalloproteinase with thrombospondin type I motifs-1
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
241475-68-3
-
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
alpha2-macroglobulin + H2O
?
-
cleavage of the bait region of alpha2-macroglobulin, complex formation with alpha2-macroglobulin is dependent on the proteolytic activity
-
?
versican + H2O
DPEAAE + ?
-
ADAMTS-1 cleaves versican at the Glu441-Ala442 bond to generate a 70000 Da fragment termed DPEAAE
-
-
?
additional information
?
-
-
enzyme plays a role in cell-cell and cell-matrix interactions, in cell adhesion and growth factor signaling
-
?
aggrecan + H2O
?
-
C-terminal spacer region of the enzyme is required for activity, substrate is a cartilage proteoglycan, cleavage site is the peptide bond Glu1871-Leu1872 within the substrates chondroitin sulfate attachment domain
-
?
proteins + H2O
peptides
-
enzyme is involved in the inflammatory process
-
?
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
versican + H2O
DPEAAE + ?
-
ADAMTS-1 cleaves versican at the Glu441-Ala442 bond to generate a 70000 Da fragment termed DPEAAE
-
-
?
additional information
?
-
-
enzyme plays a role in cell-cell and cell-matrix interactions, in cell adhesion and growth factor signaling
-
?
proteins + H2O
peptides
-
enzyme is involved in the inflammatory process
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
Zn2+
-
enzyme contains a Zn2+-binding peptidase consensus sequence HEXXH involved in catalysis
Zn2+
-
metalloprotease, contains zinc binding motif HEXXHXXXXXHD in the metalloprotease domain
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no inhibition by leupeptin, aprotinin, phenylmethylsulfonyl floride, and pepstatin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1
-
ADAMTS-1 is localized to developing mother vessel endothelial cells
additional information
-
intravenous administration of lipopolysaccharides resulted in inflammation which induced the enzyme expression exclusively in heart and kidney
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the mature processed enzyme form is soluble, the unprocessed enzyme proform is associated with the extracellular matrix via the first TSP-1 repeat that can bind to heparin
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
silencing of Adamts1 blocks the adverse effects of ethanol on collagen and elastin levels
metabolism
the enzyme is controlled by the FoxO1-sestrin 3-AMP-activated protein kinase signaling cascade and regulates ethanol-induced changes in collagen I and elastin levels
physiological function
physiological function
-
ADAMTS1 has an impact on bone mineral density and is a potent regulator of bone remodeling. Adamts1 induces parathyroid hormone levels in females and reduces osteocalcin levels in males
physiological function
expression of ADAMTS1 increases in middle-aged and old wild-type mice compared with young, whereas in SPARC (i.e. secreted protein acidic and rich in cysteine) mice only old animals show increased ADAMTS1 expression. Levels of ADAMTS1 substrate versican decrease with age only in wild-type. SPARC treatment increases secretion of collagen I and ADAMTS1 (both the 110-kDa latent and 87-kDa active forms) into the conditioned media as well as the cellular expression of transforming growth factor-beta1-induced protein (Tgfbi) and phosphorylated Smad2
physiological function
in Adamts1-deficient mice, alterations of organs like kidney, heart and aorta are found. In addition, the lack of ADAMTS1 differently affects lymphocyte and myeloid populations in the spleen and bone marrow. The substrate versican is altered the absence of the protease. the absence of ADAMTS1 creates a pro-inflammatory landscape, correlating with tumour blockade
physiological function
macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration in young mice. NOTCH1 is a target of ADAMTS1 metalloproteinase activity, which reduces Notch signaling, leading to increased satellite cell activation
physiological function
transgenic mice overexpressing ADAMTS-1 are similar to ADAMTS-1 wild-type mice pertaining collagen, elastin content and aortic diameter
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
87000
-
SDS-PAGE, variant of ADAMTS1 in the supernatant of both fibroblasts and keratinocytes
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
enzyme is a multidomain protease possessing a prodomain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail
additional information
-
enzyme is composed of a ADAM-like protease domain, a disintegrin-like, a thrombospondin type 1 repeat and a cysteine-rich domain, but no transmembrane domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
cleavage of the proform by furin at the furin cleavage site
proteolytic modification
-
enzyme is synthesized as an inactive proform, proteolytical processing of a conserved cysteine residue in its prodomain
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E386Q
additional information
E386Q
-
oligonucleotide primer mutagenesis, mutation within the zinc binding motif, inactive
E386Q
-
oligonucleotide primer mutagenesis, mutation within the zinc binding motif, loss of zinc-binding capacity, loss of activity and capacity to complex with alpha2-macroglobulin
additional information
-
construction of soluble C-terminal deletion mutants, that are still able to form complexes with alpha2-macroglobulin
additional information
-
knock-out mutant shows a phenotype with reduced growth and body weight, as well as pathological changes in the kidney structure, obstructive fibrosis, disrupted capillary networks in the adrenal gland, and hypoplastic or atrophic papillae
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+-probond and anti-v5 antibody-conjugated affinity column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
adamts-1 gene maps to chromosome 16, region C3-C5, transient expression in COS-7 cells of FLAG-tagged wild-type and deletion mutants and mutant E386Q
-
transient expression in HEK293 cells of FLAG- and His-tagged wild-type and deletion mutants, the majority of the recombinant protein is expressed in an active form without the proprotein domain
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
incubation of myocytes with ethanol increases Adamt1 mRNA without changing the overall level of Adamts1 protein
ADAMTS-1 mRNA expression is strongly, indirectly and progressively upregulated over the period of 30 min to 16 h by vascular endothelial growth factor A
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
syngeneic B16F1 melanoma model in wild type and ADAMTS1 knockout mice. Genetic deletion of ADAMTS1 in the host microenvironment results in a drastic decrease of tumor growth and metastasis. Reduced tumors in ADAMTS1 KO mice display a paradoxical increase in vascular density and vascular-related genes with an impaired vasculature, along with a minor infiltration of macrophages. ADAMTS1is involved in vascular sprouting, and melanoma xenografts show a relevant induction of its expression in stroma compartments
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
Mus musculus (P97857), Rattus norvegicus (Q9WUQ1)
Kuno, K.; Okada, Y.; Kawashima, H.; Nakamura, H.; Miyasaka, M.; Ohno, H.; Matsushima, K.
ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan
FEBS Lett.
478
241-245
2000
Mus musculus
Tang, B.L.
ADAMTS: a novel family of extracellular matrix proteases
Int. J. Biochem. Cell Biol.
33
33-44
2001
Mus musculus, Homo sapiens (Q9UHI8)
Kuno, K.; Terashima, Y.; Matsushima, K.
ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix
J. Biol. Chem.
274
18821-18826
1999
Mus musculus
Kaushal, G.P.; Shah, S.V.
The new kids on the block: ADAMTSs, potentially multifunctional metalloproteinases of the ADAM family
J. Clin. Invest.
105
1335-1337
2000
Mus musculus
Kuno, K.; Bannai, K.; Hakozaki, M.; Matsushima, K.; Hirose, K.
The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential
Biochem. Biophys. Res. Commun.
319
1327-1333
2004
Mus musculus
Mittaz, L.; Russell, D.L.; Wilson, T.; Brasted, M.; Tkalcevic, J.; Salamonsen, L.A.; Hertzog, P.J.; Pritchard, M.A.
Adamts-1 is essential for the development and function of the urogenital system
Biol. Reprod.
70
1096-1105
2004
Mus musculus
Krampert, M.; Kuenzle, S.; Thai, S.N.; Lee, N.; Iruela-Arispe, M.L.; Werner, S.
ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of fibroblasts and endothelial cells
J. Biol. Chem.
280
23844-23852
2005
Mus musculus
Shozu, M.; Minami, N.; Yokoyama, H.; Inoue, M.; Kurihara, H.; Matsushima, K.; Kuno, K.
ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary
J. Mol. Endocrinol.
35
343-355
2005
Mus musculus
Liu, Y.J.; Xu, Y.; Yu, Q.
Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively
Oncogene
25
2452-2467
2006
Mus musculus (P97857)
Brown, H.M.; Dunning, K.R.; Robker, R.L.; Pritchard, M.; Russell, D.L.
Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis
Dev. Biol.
300
699-709
2006
Mus musculus
Stankunas, K.; Hang, C.T.; Tsun, Z.Y.; Chen, H.; Lee, N.V.; Wu, J.I.; Shang, C.; Bayle, J.H.; Shou, W.; Iruela-Arispe, M.L.; Chang, C.P.
Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis
Dev. Cell
14
298-311
2008
Mus musculus
Brown, H.M.; Dunning, K.R.; Robker, R.L.; Boerboom, D.; Pritchard, M.A.; Lane, M.; Russell, D.L.
ADAMTS1 cleavage of versican mediates essential structural remodeling of the ovarian follicle and cumulus-oocyte matrix during ovulation in mice
Biol. Reprod.
83
549-557
2010
Mus musculus
Curry, T.E.
ADAMTS1 and versican: partners in ovulation and fertilization
Biol. Reprod.
83
505-506
2010
Mus musculus
Lee, Y.J.; Koch, M.; Karl, D.; Torres-Collado, A.X.; Fernando, N.T.; Rothrock, C.; Kuruppu, D.; Ryeom, S.; Iruela-Arispe, M.L.; Yoon, S.S.
Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1
Cancer Res.
70
948-956
2010
Mus musculus
Guo, C.; Wang, Y.; Liang, H.; Zhang, J.
ADAMTS-1 contributes to the antifibrotic effect of captopril by accelerating the degradation of type I collagen in chronic viral myocarditis
Eur. J. Pharmacol.
629
104-110
2010
Mus musculus
Hu, L.; Jonsson, K.B.; Andersen, H.; Edenro, A.; Bohlooly-Y, M.; Melhus, H.; Lind, T.
Over-expression of Adamts1 in mice alters bone mineral density
J. Bone Miner. Metab.
30
304-311
2011
Mus musculus
Fu, Y.; Nagy, J.A.; Brown, L.F.; Shih, S.C.; Johnson, P.Y.; Chan, C.K.; Dvorak, H.F.; Wight, T.N.
Proteolytic cleavage of versican and involvement of ADAMTS-1 in VEGF-A/VPF-induced pathological angiogenesis
J. Histochem. Cytochem.
59
463-473
2011
Mus musculus
Hong-Brown, L.Q.; Brown, C.R.; Navaratnarajah, M.; Lang, C.H.
Adamts1 mediates ethanol-induced alterations in collagen and elastin via a FoxO1-sestrin3-AMPK signaling cascade in myocytes
J. Cell. Biochem.
116
91-101
2015
Mus musculus (P97857)
Toba, H.; de Castro Bras, L.E.; Baicu, C.F.; Zile, M.R.; Lindsey, M.L.; Bradshaw, A.D.
Increased ADAMTS1 mediates SPARC-dependent collagen deposition in the aging myocardium
Am. J. Physiol. Endocrinol. Metab.
310
E1027-E1035
2016
Mus musculus (P97857)
Du, H.; Shih, C.; Wosczyna, M.; Mueller, A.; Cho, J.; Aggarwal, A.; Rando, T.; Feldman, B.
Macrophage-released ADAMTS1 promotes muscle stem cell activation
Nat. Commun.
8
669
2017
Mus musculus (P97857)
Fernandez-Rodriguez, R.; Rodriguez-Baena, F.J.; Martino-Echarri, E.; Peris-Torres, C.; Del Carmen Plaza-Calonge, M.; Rodriguez-Manzaneque, J.C.
Stroma-derived but not tumor ADAMTS1 is a main driver of tumor growth and metastasis
Oncotarget
7
34507-34519
2016
Mus musculus (P97857)
Vorkapic, E.; Folkesson, M.; Magnell, K.; Bohlooly-Y, M.; Laenne, T.; Wagsaeter, D.
ADAMTS-1 in abdominal aortic aneurysm
PLoS ONE
12
e0178729
2017
Mus musculus (P97857), Homo sapiens (Q9UHI8)
Rodriguez-Baena, F.J.; Redondo-Garcia, S.; Peris-Torres, C.; Martino-Echarri, E.; Fernandez-Rodriguez, R.; Plaza-Calonge, M.D.C.; Anderson, P.; Rodriguez-Manzaneque, J.C.
ADAMTS1 protease is required for a balanced immune cell repertoire and tumour inflammatory response
Sci. Rep.
8
13103
2018
Mus musculus (P97857)
EXTERNAL LINKS (specific for EC-Number 3.4.24.B11)
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
