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Information on EC 3.4.24.B28 - ADAM15 and Organism(s) Homo sapiens and UniProt Accession Q13444

for references in articles please use BRENDA:EC3.4.24.B28
preliminary BRENDA-supplied EC number
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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.24 Metalloendopeptidases
                3.4.24.B28 ADAM15
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This record set is specific for:
Homo sapiens
UNIPROT: Q13444
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
proteolysis of proteins
Synonyms
adam15, a disintegrin and metalloproteinase 15, adam15 isoforms i4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
a disintegrin and metalloproteinase 15
-
ADAM15 endopeptidase
-
recommended name
ADAM15 isoforms i1
-
different isoforms exist due to alternative mRNA splicing. Isoform i1 does not contain clusters of proline residues
ADAM15 isoforms i2
-
different isoforms exist due to alternative mRNA splicing
ADAM15 isoforms i3
-
different isoforms exist due to alternative mRNA splicing. Isoform i3 contains a single unique proline cluster not found in other ADAM15 isoforms
ADAM15 isoforms i4
-
different isoforms exist due to alternative mRNA splicing
ADAM15 isoforms i5
-
different isoforms exist due to alternative mRNA splicing
ADAM15 isoforms i6
-
different isoforms exist due to alternative mRNA splicing
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dabcyl-Ala-Pro-Arg-Trp-Ile-Gln-Asp-Lys(5FAM)-NH2 + H2O
?
show the reaction diagram
FRET substrate
-
-
?
dabcyl-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys(5FAM)-NH2 + H2O
?
show the reaction diagram
FRET substrate
-
-
?
Dabcyl-Leu-Arg-Glu-Gln-Gln-Arg-Leu-Lys-Ser-Lys(5FAM)-NH2 + H2O
?
show the reaction diagram
FRET substrate, based on a physiological CD23 cleavage site
-
-
?
major histocompatibility complex class I polypeptide-related sequence B + H2O
?
show the reaction diagram
ectodomain shedding
-
-
?
nephrocystin + H2O
?
show the reaction diagram
-
-
-
?
dabcyl-HGDQMAQKSK(5FAM)-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
nephrocystin + H2O
?
show the reaction diagram
-
strong co-precipitation of nephrocystin from cell lysates is specific to ADAM15 isoforms i4, i5, and i6
-
-
?
additional information
?
-
-
in contrast other ADAM15 isoforms ADAM15i3 interacts preferentially with Hck and Lyn containing proteins
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
major histocompatibility complex class I polypeptide-related sequence B + H2O
?
show the reaction diagram
ectodomain shedding
-
-
?
nephrocystin + H2O
?
show the reaction diagram
-
-
-
?
nephrocystin + H2O
?
show the reaction diagram
-
strong co-precipitation of nephrocystin from cell lysates is specific to ADAM15 isoforms i4, i5, and i6
-
-
?
additional information
?
-
-
in contrast other ADAM15 isoforms ADAM15i3 interacts preferentially with Hck and Lyn containing proteins
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-(3S)-thiomorpholinecarboxamide
i.e. TMI-1, complete inhibition at 0.01 mM
GI254023
40% inhibition at 0.1 mM
adamastat
-
sulfonamide inhibitor, binds to the active site of the ADAM15 metalloproteinase domain with a calculated binding energy of -9.0 kcal/mol.In the preferred binding mode, the biphenyl amino side chain of the inhibitor resides in the deep amphipathic S1' amino acid recognition pocket of the ADAM15 catalytic domain. Adamastat significantly inhibits the viability of UM-UC-9 and UM-UC-6 cells at 10 microM
additional information
not inhibitory: TIMP1, TIMP3, marimastat, TAPI2
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0074
dabcyl-Ala-Pro-Arg-Trp-Ile-Gln-Asp-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
0.019
dabcyl-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
0.029
Dabcyl-Leu-Arg-Glu-Gln-Gln-Arg-Leu-Lys-Ser-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.032
dabcyl-Ala-Pro-Arg-Trp-Ile-Gln-Asp-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
0.11
dabcyl-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
0.15
Dabcyl-Leu-Arg-Glu-Gln-Gln-Arg-Leu-Lys-Ser-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4300
dabcyl-Ala-Pro-Arg-Trp-Ile-Gln-Asp-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
5800
dabcyl-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
5200
Dabcyl-Leu-Arg-Glu-Gln-Gln-Arg-Leu-Lys-Ser-Lys(5FAM)-NH2
pH not specified in the publication, temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
rheumatoid arthritis synovial fibroblasts display significantly higher caspase 3/7 activity upon camptothecin and FasL exposure when ADAM15 is down-regulated by specific small interfering RNAs. There is also a marked reduction of apoptosis upon knockdown of ADAM15 protein expression
physiological function
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ADA15_HUMAN
863
0
92959
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
75000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * about 100000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
recombinant enzyme is activated both via thermolysin- and auto-activation. There is no detectable ADAM15 activity in the absence of activation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Blue Sepharose column chromatography, nickel chelate column chromatography, and DEAE anion exchange chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293 cell or CHO cell
the disintegrin domain of ADAM15 fused to human serum albumin is expressed in Pichia pastoris strain GS115
expressed as a GST-fusion protein in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ADAM15 mRNA is up to 4fold upregulated when endothelial cells are exposed to physiologic shear stress
enzyme expression is increased in pancreatic cancer cells compared to normal pancreatic tissue
the enzyme is up-regulated in the rheumatoid arthritis synovial membrane
ADAM15 expression is down-regulated in melanoma metastasis compared to primary melanoma. Interferon-gamma and tumor growth factor-beta1 down-regulate ADAM15 protein levels in melanoma cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
high expression of ADAM15 is associated with decreased overall survival and disease-free survival in non-small cell lung cancer (NSCLC) patients. shRNA-mediated knockdown of ADAM15 attenuates cell migration and invasion. ADAM15 upregulates MMP9 expression in lung cancer cells via activation of the MEK-ERK pathway. ADAM15 proteolytically cleaves and activates pro-MMP9 in vitro and interacts with MMP9 in vivo. Overexpression of ADAM15 in A-549 cells promotes cell invasion, while knocking down MMP9 attenuates cell invasive ability
medicine
-
ADAM15 ranks in the top 5% of amplified genes and its mRNA is significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. In metastatic samples, increased ADAM15 immunoreactivity is associated with increasing cancer stage and exhibits significantly stronger staining. The knockdown of ADAM15 mRNA expression significantly inhibits bladder tumor cell migration and reduces the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibits tumor growth by 45% compared to controls
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kleino, I.; Ortiz, R.M.; Yritys, M.; Huovila, A.P.; Saksela, K.
Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins
J. Cell. Biochem.
108
877-885
2009
Homo sapiens
Manually annotated by BRENDA team
Ungerer, C.; Doberstein, K.; Buerger, C.; Hardt, K.; Boehncke, W.H.; Boehm, B.; Pfeilschifter, J.; Dummer, R.; Mihic-Probst, D.; Gutwein, P.
ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma
Biochem. Biophys. Res. Commun.
401
363-369
2010
Homo sapiens
Manually annotated by BRENDA team
Boehm, B.B.; Freund, I.; Krause, K.; Kinne, R.W.; Burkhardt, H.
ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling
Arthritis Rheumatol.
65
2826-2834
2013
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Hou, Y.; Chu, M.; Du, F.F.; Lei, J.Y.; Chen, Y.; Zhu, R.Y.; Gong, X.H.; Ma, X.; Jin, J.
Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells
Biochem. Biophys. Res. Commun.
435
640-645
2013
Homo sapiens (Q13444), Homo sapiens
Manually annotated by BRENDA team
Lee, H.D.; Kim, Y.H.; Koo, B.H.; Kim, D.S.
The ADAM15 ectodomain is shed from secretory exosomes
BMB Rep.
48
277-282
2015
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Hou, Y.; Chu, M.; Du, F.; Dai, H.; Chen, Y.; Jin, J.
Expression and activity of human serum albumin recombinant human disintegrin domain of ADAM15 fusion protein
Chin. J. Biol.
26
1551-1555
2013
Homo sapiens (Q13444)
-
Manually annotated by BRENDA team
Lee, H.D.; Koo, B.H.; Kim, Y.H.; Jeon, O.H.; Kim, D.S.
Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes
FASEB J.
26
3084-3095
2012
Homo sapiens (Q13444), Homo sapiens
Manually annotated by BRENDA team
Fried, D.; Boehm, B.B.; Krause, K.; Burkhardt, H.
ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions
J. Biol. Chem.
287
21214-21223
2012
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Duan, X.; Mao, X.; Sun, W.
ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells
Mol. Med. Rep.
7
991-997
2013
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Moss, M.L.; Miller, M.A.; Vujanovic, N.; Yoneyama, T.; Rasmussen, F.H.
Fluorescent substrates for ADAM15 useful for assaying and high throughput screening
Anal. Biochem.
514
42-47
2016
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Babendreyer, A.; Molls, L.; Simons, I.M.; Dreymueller, D.; Biller, K.; Jahr, H.; Denecke, B.; Boon, R.A.; Bette, S.; Schnakenberg, U.; Ludwig, A.
The metalloproteinase ADAM15 is upregulated by shear stress and promotes survival of endothelial cells
J. Mol. Cell. Cardiol.
134
51-61
2019
Homo sapiens (Q13444)
Manually annotated by BRENDA team
Dong, D.D.; Zhou, H.; Li, G.
ADAM15 targets MMP9 activity to promote lung cancer cell invasion
Oncol. Rep.
34
2451-2460
2015
Homo sapiens (Q13444), Homo sapiens
Manually annotated by BRENDA team
Lorenzatti Hiles, G.; Bucheit, A.; Rubin, J.R.; Hayward, A.; Cates, A.L.; Day, K.C.; El-Sawy, L.; Kunju, L.P.; Daignault, S.; Lee, C.T.; Liebert, M.; Hussain, M.; Day, M.L.
ADAM15 Is functionally associated with the metastatic progression of human bladder cancer
PLoS ONE
11
e0150138
2016
Homo sapiens
Manually annotated by BRENDA team
Mattern, J.; Roghi, C.; Hurtz, M.; Knaeuper, V.; Edwards, D.; Poghosyan, Z.
ADAM15 mediates upregulation of claudin-1 expression in breast cancer cells
Sci. Rep.
9
12540
2019
Homo sapiens (Q13444)
Manually annotated by BRENDA team