Information on EC 3.4.24.B10 - ADAM12 endopeptidase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.4.24.B10
Word Map on EC 3.4.24.B10
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.24.B10
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
ADAM12 endopeptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
proteolysis of proteins
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY hide
182372-11-8
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
up-regulation of ADAM12L induces the Akt Ser-473 phosphorylation-dependent survival pathway via stimulation of beta1 integrins and activation of phosphoinositide 3-kinase, and promotes kinase activity from integrin-linked kinase immunoprecipitates
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-Fam-EFPIYDFLPAKKK-NH2 + H2O
5-Fam-EFPI + YDFLPAKKK-NH2
show the reaction diagram
-
-
-
-
?
5-Fam-FFLAQA(homophenylalanine)RSK-NH2 + H2O
5-Fam-FFLAQA + (homophenylalanine)RSK-NH2
show the reaction diagram
-
best substrate
-
-
?
5-Fam-HADLAQA(homophenylalanine)RSK-NH2 + H2O
5-Fam-HADLAQA + (homophenylalanine)RSK-NH2
show the reaction diagram
-
-
-
-
?
5-Fam-HALAQA(homophenylalanine)RSK-NH2 + H2O
5-Fam-HALAQA + (homophenylalanine)RSK-NH2
show the reaction diagram
-
-
-
-
?
5-Fam-LAQA(homophenylalanine)RSK-NH2 + H2O
5-Fam-LAQA + (homophenylalanine)RSK-NH2
show the reaction diagram
-
-
-
-
?
5-Fam-SAVSRLRAYLLPA-NH2 + H2O
5-Fam-SAVSRLR + AYLLPA-NH2
show the reaction diagram
-
-
-
-
?
betacellulin + H2O
?
show the reaction diagram
-
-
-
-
?
dabcyl-LAQA(homo)PheRSK(5FAM)-NH2 + H2O
?
show the reaction diagram
-
a 5-carboxamido-fluorescein labelled substrate
-
-
?
Dabcyl-LAQA(homophenylalanine)RSK(5-FAM)-NH2 + H2O
Dabcyl-LAQA + (homophenylalanine)RSK(5-FAM)-NH2
show the reaction diagram
-
-
-
-
?
delta-like 1 + H2O
?
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
epidermal growth factor + H2O
?
show the reaction diagram
-
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
Gelatin + H2O
?
show the reaction diagram
-
-
-
-
?
heparin binding epidermal growth factor-like growth factor + H2O
?
show the reaction diagram
-
-
-
-
?
heparin-binding epidermal growth factor + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein 5 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein-3 + H2O
?
show the reaction diagram
insulin-like growth factor binding protein-5 + H2O
?
show the reaction diagram
placental leucine aminopeptidase + H2O
?
show the reaction diagram
-
-
-
-
?
protein + H2O
peptides
show the reaction diagram
proteins + H2O
peptides
show the reaction diagram
-
-
-
?
S-carboxymethylated transferrin + H2O
?
show the reaction diagram
-
-
-
-
?
Type IV collagen + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
epidermal growth factor + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein-3 + H2O
?
show the reaction diagram
insulin-like growth factor binding protein-5 + H2O
?
show the reaction diagram
protein + H2O
peptides
show the reaction diagram
proteins + H2O
peptides
show the reaction diagram
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cu2+
-
activates, dependent on, multistep activation mechanism involving both furin cleavage and copper binding
Mg2+
-
marginal stimulatory effect
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-(2-methylpropyl)butanediamide
-
IC50: 5930 nM
(4-(N-hydroxyamino)-2R-isobutyl-3S-methylsuccinyl)-L-phenylglycine-N-methylamide
-
KB-R7785, 0.001mmol/l
1,10-phenanthroline
4-[[[6-cyano-1-[(1-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4,6,7-hexahydroquinolin-3-yl](pyridin-2-ylsulfonyl)amino]methyl]-N,N-dimethylpiperidine-1-carboxamide
-
-
Aprotinin
-
0.1 mg/ml
batimastat
-
-
BB94
-
0.01 mM
Co2+
-
0.01 mM Co2+ inhibits the activity by 80%, while increasing concentrations rescue the lost activity
endogenous matrix metalloprotease inhibitor
-
500 nM, TIMP-3
-
GM6001
-
-
Hg2+
-
-
hydroxamate inhibitor BB-94
-
slight inhibition
KB-R7785
-
0.001 mM
marimastat
MMP inhibitor III
-
-
MMP inhibitor V
-
-
MMP-3 inhibitor VIII
-
-
Mn2+
-
-
N-TIMP-1
-
N-terminal domain of TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1TACE
-
mutant (V4S/V69L/T98L/TIMP-3-ABloop) of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1[T98L]
-
mutant of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1[TIMP-2-ABloop]
-
mutant of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1[TIMP-3-ABloop]
-
mutant of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1[V4A]
-
mutant of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-1[V4S]
-
mutant of N-TIMP-1, tissue inhibitor of metalloproteinase
-
N-TIMP-2
-
N-terminal domain of TIMP-2, tissue inhibitor of metalloproteinase
-
N-TIMP-2-deltaABloop
-
mutant of N-TIMP-2, tissue inhibitor of metalloproteinase
-
N-TIMP-2TACE
-
mutant (S2T/A70S/V71L/TIMP-3-ABloop) of N-TIMP-2, tissue inhibitor of metalloproteinase
-
N-TIMP-2TACE[F34G]
-
mutant of N-TIMP-2TACE, tissue inhibitor of metalloproteinase
-
N-TIMP-2TACE[L100E]
-
mutant of N-TIMP-2TACE, tissue inhibitor of metalloproteinase
-
N-TIMP-3
-
N-[(2E)-3-(2-fluorophenyl)-2-[(phenylcarbonyl)amino]prop-2-enoyl]valine
-
IC50: 40.5 nM
N-[(2E)-3-(3-bromophenyl)-2-[(furan-2-ylcarbonyl)amino]prop-2-enoyl]glycine
-
IC50: 16.7 nM
N-[(2E)-3-(4-bromofuran-2-yl)-2-[[(5-bromofuran-2-yl)carbonyl]amino]prop-2-enoyl]alanine
-
IC50: 24.8 nM
N-[(2E)-3-furan-2-yl-2-[(furan-2-ylcarbonyl)amino]prop-2-enoyl]alanine
-
IC50: 42.3 nM
NaCl
-
-
Ni2+
-
low concentrations of Ni2+ inhibit ADAM12-S drastically
TAPI-0
-
-
TAPI-1
-
-
TAPI-2
-
-
TIMP-1
-
TIMP-2
-
TIMP-3
-
tissue inhibitor of metalloproteinase
-
tissue inhibitor of metalloproteinase-3
-
i.e. TIMP-3, possible physiological inhibitor of the enzyme
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
five SH3 domain adapter protein
-
FISH adapter protein, p165
-
PACSIN3
-
protein that interacts with the enzyme via its proline-rich region, amino acid residues 829-840, at the cytoplasmic domain, interaction is necessary for the upregulation of proHB-EGF shedding
-
stanolone
-
regulation in a bell-shaped, dose-dependent manner, maximal, 5fold increase in activity at 0.000001 mM
tissue growth factor beta
-
potent inducer of ADAM12 expression
-
transforming growth factor beta
-
ADAM-12m expression in osteoarthritic chondrocytes is selectively enhanced by transforming growth factor beta
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0145 - 0.0192
S-carboxymethylated transferrin
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12 - 0.47
S-carboxymethylated transferrin
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000032 - 0.0000125
N-TIMP-3
-
0.00011 - 0.000454
TIMP-1
-
0.0000093 - 0.000044
TIMP-2
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00593
(2R)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-(2-methylpropyl)butanediamide
Homo sapiens;
-
IC50: 5930 nM
0.000025 - 0.000028
batimastat
0.0011 - 0.0021
GM6001
0.00043 - 0.00067
marimastat
0.0006 - 0.0011
MMP inhibitor III
0.00012 - 0.00018
MMP inhibitor V
0.0015 - 0.0028
MMP-3 inhibitor VIII
0.0000405
N-[(2E)-3-(2-fluorophenyl)-2-[(phenylcarbonyl)amino]prop-2-enoyl]valine
Homo sapiens;
-
IC50: 40.5 nM
0.0000167
N-[(2E)-3-(3-bromophenyl)-2-[(furan-2-ylcarbonyl)amino]prop-2-enoyl]glycine
Homo sapiens;
-
IC50: 16.7 nM
0.0000248
N-[(2E)-3-(4-bromofuran-2-yl)-2-[[(5-bromofuran-2-yl)carbonyl]amino]prop-2-enoyl]alanine
Homo sapiens;
-
IC50: 24.8 nM
0.0000423
N-[(2E)-3-furan-2-yl-2-[(furan-2-ylcarbonyl)amino]prop-2-enoyl]alanine
Homo sapiens;
-
IC50: 42.3 nM
0.00035 - 0.0004
TAPI-0
0.001 - 0.0014
TAPI-1
0.0014 - 0.0018
TAPI-2
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7.5 - 8.5
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.5
-
enzyme is active at neutral and alkaline pH, but inactive below pH 6.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
androgen-dependent prostate cancer cell line
Manually annotated by BRENDA team
-
of pregnant women
Manually annotated by BRENDA team
-
osteoarthritic cartilage
Manually annotated by BRENDA team
-
androgen-independent prostate cancer cell line
Manually annotated by BRENDA team
-
strong reactivity in outer root sheath of catagen and telogen hair follicles
Manually annotated by BRENDA team
-
androgen-dependent prostate cancer cell line
Manually annotated by BRENDA team
-
myogenic precursor cell
Manually annotated by BRENDA team
-
androgen-independent prostate cancer cell line
Manually annotated by BRENDA team
-
cell culture
Manually annotated by BRENDA team
-
ADAM-12 is produced during allergic reaction by airway epithelial cells and might increase neutrophil recruitment within airway mucosa
Manually annotated by BRENDA team
-
interleukin-17-secreting T cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25000
-
SDS-PAGE, prodomain of ADAM12-S
95000
-
x * 95000, mature enzyme, SDS-PAGE
96000
-
x * 68000, processed recombinant enzyme, SDS-PAGE, x * 96000, recombinant enzyme proform, SDS-PAGE
100000
-
SDS-PAGE, full length ADAM12
120000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
degylcosylation with endoglycosidase H
phosphoprotein
-
c-Src kinase activity regulates ADAM12-L phosphorylation (tyrosine phosphorylation) and the c-Src-ADAM12-L interaction, the cytoplasmic tail of ADAM12-L has two Src SH3-binding sites, the high-affinity c-Src binding site is important for its cellular localization with c-Src to actin-rich structures at the cell periphery
proteolytic modification
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ADAM-12 concentration is not changed following three repeated -20C to room temperature freeze-thaw cycles, in serum at 30C a 10% change in concentration is observed after 14.8 hours. In serum at room temperature a 10% change in concentration is observed after 19.9 hours. In serum at refrigerator temperature a 10% change in concentration is observed after 51.0 hours. In whole blood at 30C 64.0% is observed after 3 days. In whole blood at room temperature 81.5% is observed after 3 days. In whole blood at refrigerator temperature 96.6% is observed after 3 days.
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange column chromatography and concanavalin A column chromatography
-
DC-6xHis column affinity chromatography
-
gelatin-Sepharose chromatography, cation exchange chromatography, and concanavalin A- or heparin-Sepharose affinity chromatography
-
gelatin-Sepharose, cation-exchange and concanavalin A affinity chromatography
-
partial, soluble recombinant protein from 293-EBNA cell and COS-1 cell medium
-
Q-Sepharose anion exchange and gelatin-Sepharose affinity chromatography
-
recombinant from COS cells
-
recombinant protein from cell line 293-EBNA
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in 293-VnR cell (derived from HEK-293 cell)
-
expressed in COS-7 cells
-
expressed in embryonic kidney cell line
-
expressed in HEK-293 cell
-
expressed in HEK-293T cells, hepatic stellate cells, rhabdomyosarcoma cells, C2C12 cells, COS7 cells, and MvLu1 cells
-
expression in a yeast two-hybrid system as GT-tagged enzyme
-
expression in CHO cells
-
expression of the soluble enzyme form ADAM 12-S in COS cells
-
expression of the soluble enzyme in COS-1 cells and in 293-EBNA cell line, coexpression of soluble enzyme and insulin-like growth factor-binding protein-3 in a Saccharomyces cerevisiae two hybrid expression system
-
expression of the soluble secreted enzyme form ADAM 12-S in cell line 293-EBNA
-
transient expression in COS-7 cells of an enzyme mutant where the signal peptide, prodomain and metalloprotease domain are exchanged for an Ig kappa-chain leader sequence, secretion to the medium
-
transient expression in COS-7 cells of the enzyme mutants, secretion to the medium
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
a significant decrease in ADAMTS-12 mRNA levels is detected in extravillous cytotrophoblasts cultured in the presence of transforming growth factor-beta1 (1 ng/ml) for 24 - 48 h
-
ADAM12 is dynamically upregulated and under the transcriptional control of protein kinase A
-
ADAM12 mRNA expression is elevated 10-30fold in malignant breast tissue and metastatic lymph nodes
-
ADAM12-L mRNA expression is an independent prognostic factor in resected p-stage I lung adenocarcinoma, and is significantly correlated with tumor differentiation stage and postoperative cancer recurrence
-
ADAMTS-12 mRNA levels in extravillous cytotrophoblasts are significantly higher than those detected in JEG-3 cell. Interleukin-1beta causes a continuous and significant increase in ADAMTS-12 mRNA levels in extravillous cytotrophoblasts over time in culture
-
expression of ADAM12 is enriched in interleukin-17 secreting T cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C179H
-
site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain, still active in complex formation with alpha2-macroglobulin
C179H/E351Q
-
site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain results in a no longer latent but inactive zymogen
D301H
-
cancer-associated mutation
G479E
-
cancer-associated mutation
G48R
-
naturally occuring mutation, statistically significant association between this polymorphism and patellofemoral osteoarthritis in male patients
L792F
-
the mutant with wild type activity is not associated with breast cancer
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine