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Information on EC 3.4.24.B10 - ADAM12 endopeptidase and Organism(s) Mus musculus and UniProt Accession Q61824
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3.4.24.B10 ADAM12 endopeptidaseSpecify your search results
Word Map
- 3.4.24.B10
-
adams
- pregnancy
-
trimester
- integrins
- metalloproteinases
- myoblasts
- papp-a
-
pregnancy-associated
- preeclampsia
-
first-trimester
- ectodomain
- thrombospondin
- protein-a
- hb-egf
-
egf-like
-
metalloprotease-disintegrins
-
gestation-specific
-
nuchal
-
disintegrin-like
- timp-3
-
adamts-7
-
invadopodia
- medicine
-
metalloproteinase-12
-
beta-hcg
- prodomain
-
second-trimester
- igfbp-5
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
adam12, adam 12, adam-12, adamts-12, adam12-s, adam12s, adam12-l, meltrin alpha, adam12l, a disintegrin and metalloprotease 12, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAM12
ADAM12-S
ADAM12
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
182372-11-8
-
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
pro-heparin-binding-epidermal growth factor-like growth factor + H2O
?
-
-
-
-
?
additional information
?
-
enzyme is a marker of skeletal muscle regeneration, binds to alpha-actinin-2 via a specific binding site, and is required for myoblast fusion
-
?
additional information
?
-
-
enzyme interacts with alpha-actinin-1 and skeletal muscle specific alpha-actinin-2 via its cytoplasmic domain, the interacation is responsible for the intracellular targeting of ADAM 12
-
?
additional information
?
-
-
enzyme provides docking sites for the Src homology 3 domain of p85alpha and thus activates PI 3-kinase by mediating its recruitment to the membrane
-
?
additional information
?
-
-
overexpression in C2C12 cells, leading to upregulation of retinoblastoma-related proteins p130, cell cycle inhibitor protein p27, and the differentiation markers myogenin and integrin alpha7A isoform, all resulting in cell cycle arrest, enzyme induces a quiescence-like phenotype and does not stimulate differentiation in myoblasts, enzyme mediated adhesion or signaling may play a role in determination of the pool of reserve cells during myoblast differentiation
-
?
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
pro-heparin-binding-epidermal growth factor-like growth factor + H2O
?
-
-
-
-
?
additional information
?
-
enzyme is a marker of skeletal muscle regeneration, binds to alpha-actinin-2 via a specific binding site, and is required for myoblast fusion
-
?
additional information
?
-
-
overexpression in C2C12 cells, leading to upregulation of retinoblastoma-related proteins p130, cell cycle inhibitor protein p27, and the differentiation markers myogenin and integrin alpha7A isoform, all resulting in cell cycle arrest, enzyme induces a quiescence-like phenotype and does not stimulate differentiation in myoblasts, enzyme mediated adhesion or signaling may play a role in determination of the pool of reserve cells during myoblast differentiation
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
metalloprotease domain is not essential for inhibition of cell cycle progression by the enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
N-TIMP-3 variants that lack MMP inhibitory activity but retain the ability to inhibit ADAM17/TACE fail to inhibit ADAM12
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
highly up-regulated in newly formed muscle fibers, enzyme is a marker of skeletal muscle regeneration, strongly binds to alpha-actinin-2 at the enzymes cytoplasmic tail
-
cell culture, reserve cells, enzyme mediated adhesion or signaling may play a role in determination of the pool of reserve cells during myoblast differentiation, enzyme induces a quiescence-like phenotype and does not stimulate differentiation in myoblasts
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
enzyme interacts with alpha-actinin-1 and skeletal muscle specific alpha-actinin-2 via its cytoplasmic domain, the intercation is responsible for the intracellular targeting of ADAM 12
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
enzyme inhibition is sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function
physiological function
the enzyme is an essential molecules for hypoxia-induced impairment of neural vascular barrier function
malfunction
-
about 30% of ADAM12 deficient mice die during the early neonatal period and 30% of viable homozygotes display a reduction in their interscapular brown adipose tissue. ADAM12 null mice are more resistant to obesity induced by high-fat diet and exhibit improved insulin sensitivity compared to wild type mice
metabolism
-
the transforming growth factor-beta1 signaling pathway is correlated with ephrin-A1 cleavage by isoform ADAM12L
physiological function
physiological function
-
the enzyme plays a role in controlling trophoblast invasion and during neovascularization and placental development
physiological function
-
the enzyme functions during neovascularization and placental development and is important for trophoblast invasion. Overexpression of either ADAM12 isoform increases proliferation of breast cancer cells
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
45000
-
SDS-PAGE, truncated protein ADAM12-deltaPM lacking the pro- and metalloprotease domain
90000
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D301H
-
the mutation ihibits the proteolytic processing and activation of ADAM12
G479E
-
the mutation ihibits the proteolytic processing and activation of ADAM12
L73P
-
mutant with properties similar to wild-type concerning the cell cycle of C2C12 cells
L792F
-
the mutation ihibits the proteolytic processing and activation of ADAM12
additional information
additional information
construction of deletion mutants comprising the cytoplasmic tail with or without the alpha-actinin-2-binding site
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
streptavidin-Sepharose chromatography and concanavalin A-Sepharose chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the enzymes cytoplasmic tail including or missing the alpha-actinin-2-binding site, tagged with a myristolation motif in C2C12 myoblast cells, in vitro transcription and translation of the enzyme, expression of the enzymes cytoplasmic tail including or missing the alpha-actinin-2-binding site as GST-fusion proteins in Escherichia coli XL-1 Blue
expression as GFP-pleckstrin homology domain fusion protein in C2C12 cells, targeted to the plasma membrane by a myristoylation motif
-
expression as soluble GST-fusion protein in Escherichia coli, and expression of an enzyme fragment, comprising amino acid residues 743-903 of the cytoplasmic domain, as GFP-fusion protein in C2C12 cells
-
overexpression in C2C12 cells, leading to upregulation of retinoblastoma-related proteins p130, cell cycle inhibitor protein p27, and the differentiation markers myogenin and integrin alpha7A isoform, all resulting in cell cycle arrest
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression by astrocytes is increased in brain regions affected by cuprizone-induced demyelination
-
inhibition of canonical Notch signaling increases ADAM12 long isoform expression and trophoblast invasion
-
spatiotemporally expressed in decidualizing stromal cells in intact pregnant females and in pseudopregnant mice undergoing artificially induced decidualization
-
transforming growth factor beta1 is a inducer of ADAM12 mRNA and protein in fibroblasts and in mammary epithelial cells (also in human mammary epithelial cells)
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
low serum levels of the enzyme are associated with spontaneous pre-term delivery and IUGR
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cao, Y.; Kang, Q.; Zolkiewska, A.
Metalloprotease-disintegrin ADAM 12 interacts with alpha-actinin-1
Biochem. J.
357
353-361
2001
Mus musculus
Galliano, M.F.; Huet, C.; Frygelius, J.; Polgren, A.; Wewer, U.M.; Engvall, E.
Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha-actinin-2, is required for myoblast fusion
J. Biol. Chem.
275
13933-13939
2000
Mus musculus (Q61824)
Kang, Q.; Cao, Y.; Zolkiewska, A.
Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells
J. Biol. Chem.
276
24466-24472
2001
Mus musculus
Cao, Y.; Zhao, Z.; Gruszczynska-Biegala, J.; Zolkiewska, A.
Role of metalloprotease disintegrin ADAM12 in determination of quiescent reserve cells during myogenic differentiation in vitro
Mol. Cell. Biol.
23
6725-6738
2003
Mus musculus
Kveiborg, M.; Froehlich, C.; Albrechtsen, R.; Tischler, V.; Dietrich, N.; Holck, P.; Kronqvist, P.; Rank, F.; Mercurio, A.M.; Wewer, U.M.
A role for ADAM12 in breast tumor progression and stromal cell apoptosis
Cancer Res.
65
4754-4761
2005
Mus musculus
Masaki, M.; Kurisaki, T.; Shirakawa, K.; Sehara-Fujisawa, A.
Role of meltrin {alpha} (ADAM12) in obesity induced by high-fat diet
Endocrinology
146
1752-1763
2005
Mus musculus
Yi, H.; Gruszczynska-Biegala, J.; Wood, D.; Zhao, Z.; Zolkiewska, A.
Cooperation of the metalloprotease, disintegrin, and cysteine-rich domains of ADAM12 during inhibition of myogenic differentiation
J. Biol. Chem.
280
23475-23483
2005
Mus musculus
Kveiborg, M.; Albrechtsen, R.; Rudkjaer, L.; Wen, G.; Damgaard-Pedersen, K.; Wewer, U.M.
ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation
J. Bone Miner. Res.
21
1288-1296
2006
Mus musculus
Peduto, L.; Reuter, V.E.; Sehara-Fujisawa, A.; Shaffer, D.R.; Scher, H.I.; Blobel, C.P.
ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression
Oncogene
25
5462-5466
2006
Mus musculus
Jorgensen, L.H.; Jensen, C.H.; Wewer, U.M.; Schroder, H.D.
Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice
Am. J. Pathol.
171
1599-1607
2007
Mus musculus
Kveiborg, M.; Albrechtsen, R.; Couchman, J.R.; Wewer, U.M.
Cellular roles of ADAM12 in health and disease
Int. J. Biochem. Cell Biol.
40
1685-1702
2008
Homo sapiens, Mus musculus
Dyczynska, E.; Syta, E.; Sun, D.; Zolkiewska, A.
Breast cancer-associated mutations in metalloprotease disintegrin ADAM12 interfere with the intracellular trafficking and processing of the protein
Int. J. Cancer
122
2634-2640
2008
Mus musculus
Baertling, F.; Kokozidou, M.; Pufe, T.; Clarner, T.; Windoffer, R.; Wruck, C.J.; Brandenburg, L.O.; Beyer, C.; Kipp, M.
ADAM12 is expressed by astrocytes during experimental demyelination
Brain Res.
1326
1-14
2010
Mus musculus
Zhang, L.; Guo, W.; Chen, Q.; Fan, X.; Zhang, Y.; Duan, E.
Adam12 plays a role during uterine decidualization in mice
Cell Tissue Res.
338
413-421
2009
Mus musculus
Solomon, E.; Li, H.; Muggy, S.D.; Syta, E.; Zolkiewska, A.
The role of SnoN in transforming growth factor beta1-induced expression of metalloprotease-disintegrin ADAM12
J. Biol. Chem.
285
21969-21977
2010
Mus musculus
Ieguchi, K.; Tomita, T.; Omori, T.; Komatsu, A.; Deguchi, A.; Masuda, J.; Duffy, S.L.; Coulthard, M.G.; Boyd, A.; Maru, Y.
ADAM12-cleaved ephrin-A1 contributes to lung metastasis
Oncogene
33
2179-2190
2014
Mus musculus
Aghababaei, M.; Beristain, A.
The Elsevier trophoblast research award lecture: Importance of metzincin proteases in trophoblast biology and placental development: A focus on ADAM12
Placenta
36
S11-S19
2015
Mus musculus
-
Aghababaei, M.; Beristain, A.G.
The Elsevier Trophoblast Research Award Lecture Importance of metzincin proteases in trophoblast biology and placental development a focus on ADAM12
Placenta
36 Suppl 1
S11-S19
2015
Mus musculus
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