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Information on EC 3.4.24.B9 - ADAM9 endopeptidase
for references in articles please use BRENDA:EC3.4.24.B9preliminary BRENDA-supplied EC number
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3.4.24.B9 ADAM9 endopeptidaseSpecify your search results
Word Map
- 3.4.24.B9
-
adams
- metastasis
- ectodomains
- metalloproteases
- alpha-secretase
- hb-egf
- medicine
-
adam-15
-
non-amyloidogenic
The enzyme appears in viruses and cellular organisms
Synonyms
adam9, adam-9, adam 9, mdc-9, meltrin gamma, adam metallopeptidase domain 9, a disintegrin and metalloproteinase domain 9, mdc9/meltrin-gamma/adam9, meltrin-gamma, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
a disintegrin and metalloproteinase domain 9
ADAM 9
ADAM metallopeptidase domain 9
ADAM9
cellular disintegrin-related protein
M12.209
MDC9
meltrin gamma
meltrin-gamma
metalloprotease ADAM9
additional information
additional information
-
ADAM9 is a widely expressed and particularly polyvalent member of the multifunctional ADAM family of proteins
additional information
-
ADAM9 is a widely expressed and particularly polyvalent member of the multifunctional ADAM family of proteins
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
252565-22-3
-
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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
amyloid precursor protein + H2O
90-100 kDa non-amyloid N-terminal protein fragment
-
alpha-secretase activity
-
?
EVHHQKLVFFAE + H2O
EVHH + QKLVFFAE
-
peptides derived from beta-amyloid precursor protein, comprises the predicted cleavage site
-
?
heparin-binding EGF-like growth factor + H2O
heparin-binding EGF-like growth factor fragment
-
cooperative action with bound protein kinase C, membrane-anchored substrate, ectodomain shedding
soluble product
?
insulin B chain + H2O
3 peptides
-
cleavage sites are Tyr16-Leu17 and Tyr26-Thr27
-
?
Mca-PLAQAV-Dpa-RSSSR-NH2 + H2O
Mca-PLAQA + V-Dpa-RSSSR-NH2
-
quenched fluorescent substrate
-
?
SMAPGAVHLPQP + H2O
SMAPGAVH + LPQP
-
peptides derived from P75 TNF-receptor, comprises the predicted cleavage site
-
?
SPLAQAVRSSSR + H2O
SPLA + QAVRSSSR
-
peptides derived from TNF-alpha, comprises the predicted cleavage site
-
?
SPLAQAVRSSSR + H2O
SPLAQAVRS + SSR
-
peptides derived from TNF-alpha, comprises the predicted cleavage site
-
?
transmembrane collagen XVII + H2O
soluble collagen ectodomain
-
substrate protein is an endothelial adhesion molecule on the surface of keratinocytes, protein is shed from the cell surface
cells show altered motility
?
amyloid precursor protein + H2O
?
-
enzyme shows alpha-secretase activity
-
?
amyloid precursor protein + H2O
?
enzyme shows alpha-secretase activity
-
?
amyloid precursor protein + H2O
?
-
enzyme shows alpha-secretase activity, the alpha-secretase might be composed of several ADAM enzymes in a complexe
-
?
beta-casein + H2O
?
-
recombinant metalloprotease domain is catalytically active against beta-casein
-
?
Fibronectin + H2O
?
-
recombinant metalloprotease domain is catalytically active against fibronectin
-
?
Gelatin + H2O
?
-
recombinant metalloprotease domain is catalytically active gelatin
-
?
pro-heparin-binding EGF-like growth factor + H2O
?
-
cooperative action with bound protein kinase C, membrane-anchored substrate, ectodomain shedding
-
?
proteins + H2O
peptides
enzymes of the ADAM family play importants roles in cell-cell fusion, intracellular signaling, and other cellular functions
-
?
additional information
?
-
-
interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
-
?
additional information
?
-
-
the enzyme interacts in a RGD motif-independent manner with the alphaVbeta5-domain of integrins, e.g. on the surface of myeloma but not lymphoblastoid cells, dependent on cations Ca2+ or Mn2+
-
?
additional information
?
-
-
potential ADAM-9 sheddase substrates include growth factors and cytokines, which have been linked to atherosclerosis
-
-
?
additional information
?
-
-
ADAM-9 is capable of binding to alpha6beta1 and alphanubeta5 integrins
-
-
?
additional information
?
-
-
interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
-
?
additional information
?
-
-
regulation of metalloprotease desintegrins via a cysteine-switch mechanism
-
?
additional information
?
-
-
enzyme can cleave and release epidermal growth factor and FGFR2iiib from cells
-
-
?
additional information
?
-
-
enzyme is a polyvalent ligand, through its disintegrin domain, for multiple renal integrins of the beta1 class
-
-
?
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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
amyloid precursor protein + H2O
?
-
enzyme shows alpha-secretase activity, the alpha-secretase might be composed of several ADAM enzymes in a complexe
-
?
heparin-binding EGF-like growth factor + H2O
heparin-binding EGF-like growth factor fragment
-
cooperative action with bound protein kinase C, membrane-anchored substrate, ectodomain shedding
soluble product
?
pro-heparin-binding EGF-like growth factor + H2O
?
-
cooperative action with bound protein kinase C, membrane-anchored substrate, ectodomain shedding
-
?
transmembrane collagen XVII + H2O
soluble collagen ectodomain
-
substrate protein is an endothelial adhesion molecule on the surface of keratinocytes, protein is shed from the cell surface
cells show altered motility
?
proteins + H2O
peptides
enzymes of the ADAM family play importants roles in cell-cell fusion, intracellular signaling, and other cellular functions
-
?
additional information
?
-
-
interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
-
?
additional information
?
-
-
the enzyme interacts in a RGD motif-independent manner with the alphaVbeta5-domain of integrins, e.g. on the surface of myeloma but not lymphoblastoid cells, dependent on cations Ca2+ or Mn2+
-
?
additional information
?
-
-
potential ADAM-9 sheddase substrates include growth factors and cytokines, which have been linked to atherosclerosis
-
-
?
additional information
?
-
-
interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
-
?
additional information
?
-
-
regulation of metalloprotease desintegrins via a cysteine-switch mechanism
-
?
additional information
?
-
-
enzyme can cleave and release epidermal growth factor and FGFR2iiib from cells
-
-
?
additional information
?
-
-
enzyme is a polyvalent ligand, through its disintegrin domain, for multiple renal integrins of the beta1 class
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
interaction of the enzyme with integrins is dependent on Ca2+ or Mn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
brefeldin A
-
blocks processing of the enzyme precursor by blocking the vesicle budding in the endoplasmic reticulum
Hydroxamates
-
metalloprotease inhibitors, derivatives FN-439, BB3103, BB 3241, and IC-3
TIMP-3
i.e. tissue inhibitor of metalloproteinases-3, inhibition at 10 nM
-
additional information
-
interaction of the enzyme with integrins is inhibited by antibodies against the alphaVbeta5-domain of integrin
-
additional information
-
no inhibition by the metalloprotease inhibitors TIMP-1, -2, and -4
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
stanolone
-
upregulation, 1.5fold increase in activity at 0.000001 mM, 1.7fold at 0.00001 mM
additional information
ADAM9 does not respond to stimulation with phorbol esters, calcium ionophore or phosphatase inhibitors
-
Protein kinase C
-
binds to the enzyme at its cytoplasmic part and cooperates in cleavage of EGF-like growth factor
-
Protein kinase C
-
phosphorylation of the enzyme by protein kinase C activates the enzyme, phosphorylation is stimualted by phorbol 12-myristate 13-acetate
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00005
batimastat
Mus musculus
pH not specified in the publication, temperature not specified in the publication
0.00072
GM6001
Mus musculus
pH not specified in the publication, temperature not specified in the publication
0.00048
GW280264X
Mus musculus
pH not specified in the publication, temperature not specified in the publication
0.00013
marimastat
Mus musculus
pH not specified in the publication, temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
644075, 649562, 651308, 651956, 653225, 653737, 668073, 668145, 668152, 668164, 668979, 677587, 680831, 682830, 710800, 710868, 712114, 719607, 719997
-
-
brenda
native short form of ADAM9 lacking the transmembrane and the cytoplasmic domains due to a deletion in the EGF-like domain
SwissProt
brenda
recombinant enzyme, expression in A-549 and EBC-1 cell. Enzyme overexpression results in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha3 and beta1 subunits. Administration of enzyme overexpressing A-549 cells to mice results in micrometastatic foci in brain and multiple metastatic colonies in the lungs
-
-
brenda
recombinant enzyme, expression in human colon cancer cell line HT29 cells. Overexpression of enzyme enhances growth factor-mediated induction of endocytosis and dynamic recycling of E-cadherin. Enzyme constitutively interacts with E-cadherin, the two proteins co-localize at the plasma membrane
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
carotid and femoral arteries, only weak ADAM-9 expression from thyroid artery without atherosclerosis
brenda
-
grade 3, CIN lesions are premalignant changes
brenda
-
lung cancer cell line, enzyme mRNA levels are significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines
brenda
-
synovial membrane-like interface tissue is collected from the proximal bone-cement or bone-stem interfaces around aseptically loosened femoral stems
brenda
-
cells secrete a alternatively spliced variant of enzyme promoting carcinoma invasion
brenda
expression of full length and short enzyme form, with higher level of the short form than in other tissues
brenda
-
in advanced human atherosclerotic plaques of aorta and carotid and femoral arteries, high expression level
brenda
-
ADAM-9 is expressed in human melanoma at the tumor-stroma border where direct or indirect interactions between tumor cells and fibroblasts occur
brenda
-
stromal liver myofibroblast, enzyme expression particularly by cells localized within the tumor stroma at the invasive front
brenda
-
recombinant enzyme promotes a fivefold increase in interleukin IL-6, but not IL-1beta mRNA. Enzyme binds directly to alphabeta5 integrin
brenda
-
elevated level of enzyme in malignant compared to benign tissue. Increase in enzyme protein and mRNA upon exposure of prostate cells to stress conditions. Inhibition of stress-induction of enzyme by actinomycin D and cycloheximide
brenda
-
in normal epithelium, CIN3 lesions, and squamous cell carcinomas
brenda
additional information
-
prostate cancer cell, elevated level of enzyme during the transition of cells from androgen-dependent to androgen-independent and metastatic state. Induction of enzyme is abrogated by the antioxidant ebselen or the enzyme catalase
brenda
-
study on expression patterns of enzymes ADAM9, ADAM10, and ADAM 17 during pancreas ontogeny. The three enzymes are expressed in the pancreas anlagen. During development, ADAM9 becomes restricted to the insulin-producing beta-cells
brenda
additional information
-
study on several human skin melanoma and melanoma cell lines. In melanoma, enzyme expression is restricted to the melanoma cells within the invading front. Enzyme is detected in melanoma cells and in peritumoral stromal fibroblasts, but absent in fibroblasts distal to the tumor site. In melanoma cell lines, enzyme is expressed in varying amounts in all cell lines studied. Downregulation of enzyme expression upon culture of cells within 3-dimensional latticies of fibrillar type I collagen, but not in the polysaccharide alginate
brenda
additional information
-
ADAM-9 quantitative real-time PCR expression analysis
brenda
additional information
-
ADAM9 expression is low in the squamous epithelium of the cervix, but is increased in CIN3 lesions as well as squamous cell carcinomas, only weak expression of ADAM9 in the normal cervical epithelium
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
ADAM9 localises to cell-cell junctions and colocalises with cell-cell junction proteins in endothelial cells. Expression is required in two adjacent cells for localisation to cell-cell junctions. ADAM9 can self-associate through ectodomain interactions. The soluble ADAM9 ectodomain cannot increase endothelial monolayer permeability or inhibit monocyte-endothelial adhesion, but can inhibit monocyte-endothelial transmigration
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
silencing of ADAM-9 in melanoma cells significantly reduces cell adhesion to fibroblasts. Ablation of ADAM-9 in fibroblasts almost completely abolishes these cellular interactions and melanoma cell invasion in vitro
physiological function
additional information
physiological function
-
ADAM-9 interaction with alpha6beta1 integrin regulates fibroblast motility, and alpha6beta1 integrin can induce the mobility of several cell types including macrophages. ADAM-9 is involved in advanced human atherosclerosis and might play roles in the monocyte homing, migration, or proliferation in aorta, carotid, and femoral arteries. ADAM-9 is also involved both in ectodomain shedding and cell interactions through integrin binding. Potential ADAM-9 sheddase substrates include growth factors and cytokines, which are linked to atherosclerosis
physiological function
-
ADAM9 is a member of the ADAM family which is involved in cellular processes like cell adhesion, migration and signalling, involvement of this protease in cervical carcinogenesis, overview
physiological function
-
fibroblasts adhere to the adhesive domains of ADAM-9 in the presence of Mn2+ ions. ADAM-9 expression plays an important role in mediating cell-cell contacts between fibroblasts and melanoma cells. These interactions contribute to proteolytic activities required during invasion of melanoma cells
physiological function
-
the enzyme is implicated in auto and paracrine regulation of invasiveness in A-549 cells
physiological function
coculture of melanoma cells in the presence of ADAM-9-/- fibroblasts leads to increased melanoma cell proliferation and reduced apoptosis as compared with control cocultures. TIMP-1 and sTNFRI are the two relevant factors expressed in increased amounts in culture supernatants from ADAM-9-/- fibroblasts. TIMP-1 is associated with induced melanoma cell proliferation, whereas soluble TNFR1 mediates the reduced cellular apoptosis in vitro. In vivo, injection of murine melanoma cells into the flank of ADAM-9-/- animals results in the development of significantly larger tumors than in wild-type animals as a result of increased proliferation and decreased apoptosis of melanoma cells
physiological function
aberrant overexpression of ADAM9 is found in both gastric cancer tissues and cell lines. Knockdown of ADAM9 in gastric cancer SGC-7901 cells induces a dramatic suppression of cell proliferation along with the arrest of the cell cycle in the G0/G1 phase. The 3' untranslated region of ADAM9 mRNA may be bound by miR-126, a suppressor in gastric cancer. Overexpression of miR-126 significantly downregulates ADAM9 in the gastric cancer cells
physiological function
ADAM9 enhances the expression of the pro-migratory protein CDCP1 to promote lung metastasis. Endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 is associated with high migration ability in lung cancer cells
physiological function
-
Adam9-/- mice are protected from emphysema development, small-airway fibrosis, and airway mucus metaplasia. Cigarette smoke-exposed Adam9-/- mice have reduced lung macrophage counts, alveolar septal cell apoptosis, lung elastin degradation, and shedding of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor in BAL fluid samples
physiological function
cells lacking ADAM9 show a significant reduction in infection efficiency by encephalomyocarditis virus EMCV. Pharmacological inhibition of the metalloproteinase activity of ADAM9 does not affect virus infection. Reconstitution of inactive ADAM9 in knockout cells restores susceptibility to EMCV. ADAM9 facilitates attachment of EMCV to the cell surface
additional information
-
ADAM9 is a widely expressed and particularly polyvalent member of the multifunctional ADAM family of proteins
additional information
-
ADAM9 is a widely expressed and particularly polyvalent member of the multifunctional ADAM family of proteins
additional information
-
promoter polymorphisms, which regulate ADAM9 transcription, are protective against sporadic Alzheimer's disease
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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). ADAM9_HUMAN
819
0
90556
Swiss-Prot
other Location (Reliability: 2)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
-
x * 79000, processed mature enzyme, SDS-PAGE, x * 110000, enzyme proform, SDS-PAGE
12000
-
x * 84000, processed enzyme, x * 12000, enzyme proform, SDS-PAGE
79000
-
x * 79000, processed mature enzyme, SDS-PAGE, x * 110000, enzyme proform, SDS-PAGE
80000
84000
84000
-
x * 84000, processed enzyme, x * 12000, enzyme proform, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
-
x * 79000, processed mature enzyme, SDS-PAGE, x * 110000, enzyme proform, SDS-PAGE
additional information
-
enzyme binds directly to alpha6beta4 and alpha2beta1 integrins through the disintegrin domain
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
-
N-glycosylation of endopeptidase H-sensitive precursor and mature enzyme
proteolytic modification
-
cleavage by furin-like endopeptidase, also the recombinant enzyme is cleaved in Pichia pastoris
proteolytic modification
-
cleavage of prodomain by furin, interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
proteolytic modification
-
cleavage of pro-domain by furin-type pro-protein convertase before the protein is secreted to the cell surface
proteolytic modification
-
cleavage of prodomain by furin, interaction with endophilin I and SH3PX1, a SH3 domain- and phox homolog domain-containing protein, which may have a regulatory role by inhibiting the processing of the enzyme
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
ADAM9 genomic sequence and mutation analysis determining single-nucleotide polymorphisms, ADAM9 is associated with the gPRA candidate locus for generalized progressive retinal atrophy, a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, determined by genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions. Mapping the gPRA locus and identification of an ADAM9 partial deletion, overview
additional information
-
ADAM9 genomic sequence and mutation analysis determining single-nucleotide polymorphisms, ADAM9 is associated with the gPRA candidate locus for generalized progressive retinal atrophy, a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, determined by genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions. Mapping the gPRA locus and identification of an ADAM9 partial deletion, overview
additional information
-
construction of a GST-enzyme disintegrin domain fusion protein
additional information
-
enzyme expression in tumor cell lines induces a highly invasive phenotype, protease activity of enzyme is required for invasion
additional information
-
identification of null mutations in the ADAM metallopeptidase domain 9, ADAM9, gene in four consanguineous families with recessively inherited early-onset cone-rod dystrophy, a group of genetically and phenotypically heterogenous retinal disorders, which is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors, phenotype, overview
additional information
-
screening of the ADAM9 gene promoter region identifies four polymorphisms: -542C/T (rs10105311), -600A/C (rs7840270), -963A/G (rs6991968) and -1314T/C (rs7006414), genotyping and phenotyping, overview. Both -963G/-1314C and -963A/-1314C have 1.5-1.8fold and 1.4-1.7fold higher transcriptional activity, respectively, than -963A/-1314T
additional information
-
construction of several deletion mutants lacking amino acids of the cytoplasmic region by site-directed mutagenesis
additional information
-
site-directed mutagenesis of the furin cleavage site and of the cysteine-switch region results in highly reduced precursor processing, construction of a deletion mutant resulting in a soluble enzyme form
additional information
-
enzyme overexpression in A-549 and EBC-1 cells results in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha3 and beta1 subunits. Administration of enzyme overexpressing A-549 cells to mice results in micrometastatic foci in brain and multiple metastatic colonies in the lungs
additional information
-
enzyme-deficient W10 animals, tumors are well-differentiated, whereas enzyme wild-type W10 animals show predominantly poorly differentiated, and in some cases significantly larger, tumors
additional information
-
expression of intact enzyme and a series of deletion constructs sequentially lacking the metalloprotease domain and the disintegrin domain assembled as chimeras with a C-terminal GFP tag. Stable expression of constructs on the surface of HEK-293 cells significantly decreases adhesion to types I and IV collagen, vitronectin and laminin, but has little effect on adhesion to fibronectin
additional information
-
overexpression of enzyme enhances growth factor-mediated induction of endocytosis and dynamic recycling of E-cadherin in the human colon cancer cell line HT-29. Enzyme constitutively interacts with E-cadherin, the two proteins co-localize at the plasma membrane
additional information
-
reduced photoreceptor responses occur in Adam9 knockout mice. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium cells are disorganized and contact between photoreceptor outer segments, POSs, and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages are also apparent in older mice, phenotypes, overview
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
ADAM9 gene, DNA and amino acid sequence determination and analysis, screening and analysis of the promoter region, expression of mutants iin SH-SY5Y and HeLa cells
-
DNA sequence determination and analysis, expression of the short enzyme form, lacking the transmembrane and the cytoplasmic domains due to a deletion in the EGF-like domain, in COS cells, coexpression of amyloid precursor protein
expression of GST-enzyme disintegrin domain fusion protein Escherichia coli strain BL21
-
expression of GST-fusion cytoplasmic enzyme domain in a two-hybrid system in Saccharomyces cerevisiae strain HF7c
-
expression of GST-linked cytoplasmic region in Escherichia coli, coeexpression of the enzyme and protein kinase C in COS-7 cells, overexpression of wild-type and deletion mutants in Vero-H cells
-
expression of Sec-tagged wild-type and metalloprotease domain deletion mutant in COS-7 cells
-
expression of soluble enzyme form, nucleotides 1-1253, with a Myc-epitope in COS-7 cells
-
expression of the metalloprotease domain in Pichia pastoris, processing and secretion to the medium
-
gene ADAM9, DNA and amino acid sequence determination and analysis, located on chromosome 16, associated with the gPRA candidate locus for generalized progressive retinal atrophy, a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, determined by genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions. Quantitative real-time RT-PCR expression ADAM9 analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
3 h exposure to 1 mM H2O2 induces ADAM9 expression and ADAM-specific metalloprotease activity in A549 cells
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
all three enzymes ADAM9, ADAM12, and ADAM15 are significantly upregulated in gastric cancer compared to non-neoplastic foveolar epithelium. Anti-ADAM9 and anti-ADAM15 antibodies inhibit cell growth
medicine
-
elevated level of enzyme in malignant compared to benign prostate tissue. Increase in enzyme protein and mRNA upon exposure of prostate cells to stress conditions. Inhibition of stress-induction of enzyme by actinomycin D and cycloheximide. Decrease of enzyme expression results in apoptotic cell death in prostate cancer cells
medicine
-
enzyme overexpression in A-549 and EBC-1 cells results in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha3 and beta1 subunits. Administration of enzyme overexpressing A-549 cells to mice results in micrometastatic foci in brain and multiple metastatic colonies in the lungs
medicine
-
in melanoma, enzyme expression is restricted to the melanoma cells within the invading front. Enzyme is detected in melanoma cells and in peritumoral stromal fibroblasts, but absent in fibroblasts distal to the tumor site. In melanoma cell lines, enzyme is expressed in varying amounts in all cell lines studied. Downregulation of enzyme expression upon culture of cells within 3-dimensional latticies of fibrillar type I collagen, but not in the polysaccharide alginate
medicine
-
lung cancer cell line EBC-1, enzyme mRNA levels are significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines
medicine
-
secreted form of enzyme promotes carcinoma invasion through tumor-stromal interactions
medicine
-
significantly higher level of enzyme expression in malignant plasma cells than in other cell populations present in bone marrow
medicine
injection of murine melanoma cells into the flank of ADAM-9-/- animals resultsin the development of significantly larger tumors than in wild-type animals as a result of increased proliferation and decreased apoptosis of melanoma cells
medicine
aberrant overexpression of ADAM9 is found in both gastric cancer tissues and cell lines. The expression of ADAM9 is significantly correlated with patient clinicopathological features including tumor size, local invasion, lymph node metastasis and tumor-node-metastasis stage. Knockdown of ADAM9 in gastric cancer SGC-7901 cells, which present the highest ADAM9 expression among the cell lines, induces a dramatic suppression of cell proliferation along with the arrest of the cell cycle in the G0/G1 phase. The 3' untranslated region of ADAM9 mRNA may be bound by miR-126, a suppressor in gastric cancer. Overexpression of miR-126 significantly downregulates ADAM9 in the gastric cancer cells
medicine
ADAM9 enhances the expression of the pro-migratory protein CDCP1 to promote lung metastasis. Endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 is associated with high migration ability in lung cancer cells
medicine
ADAM9 staining is increased in lung epithelial cells and macrophages in smokers and even more so in patients with chronic obstructive pulmonary disease COPD. ADAM9 staining correlates directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 percent predicted. Bronchial epithelial cell ADAM9 mRNA levels are higher in patients with COPD than control subjects and correlate directly with pack-year smoking history
medicine
cells lacking ADAM9 show a significant reduction in infection efficiency by encephalomyocarditis virus EMCV. Pharmacological inhibition of the metalloproteinase activity of ADAM9 does not affect virus infection. Reconstitution of inactive ADAM9 in knockout cells restores susceptibility to EMCV. ADAM9 facilitates attachment of EMCV to the cell surface
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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
Homo sapiens (Q13443), Mus musculus (Q61072)
brenda
Asai, M.; Hattori, C.; Szabo, B.; Sasagawa, N.; Maruyama, K.; Tanuma, S.I.; Ishiura, S.
Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase
Biochem. Biophys. Res. Commun.
301
231-235
2003
Homo sapiens
brenda
Zhou, M.; Graham, R.; Russell, G.; Croucher, P.I.
MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin
Biochem. Biophys. Res. Commun.
280
574-580
2001
Homo sapiens
brenda
Hotoda, N.; Koike, H.; Sasagawa, N.; Ishiura, S.
A secreted form of human ADAM9 has an alpha-secretase activity for APP
Biochem. Biophys. Res. Commun.
293
800-805
2002
Homo sapiens (Q13443), Homo sapiens
brenda
Koike, H.; Tomioka, S.; Sorimachi, H.; Saido, T.C.; Maruyama, K.; Okuyama, A.; Fujisawa-Sehara, A.; Ohno, S.; Suzuki, K.; Ishiura, S.
Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein
Biochem. J.
343
371-375
1999
Mus musculus
brenda
Izumi, Y.; Hirata, M.; Hasuwa, H.; Iwamoto, R.; Umata, T.; Miyado, K.; Tamai, Y.; Kurisaki, T.; Sehara-Fujisawa, A.; Ohno, S.; Mekada, E.
A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor
EMBO J.
17
7260-7272
1998
Mus musculus
brenda
Amour, A.; Knight, C.G.; English, W.R.; Webster, A.; Slocombe, P.M.; Knauper, V.; Docherty, A.J.; Becherer, J.D.; Blobel, C.P.; Murphy, G.
The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs
FEBS Lett.
524
154-158
2002
Homo sapiens
brenda
Howard, L.; Nelson, K.K.; Maciewicz, R.A.; Blobel, C.P.
Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1
J. Biol. Chem.
274
31693-31699
1999
Homo sapiens, Mus musculus
brenda
Roghani, M.; Becherer, J.D.; Moss, M.L.; Atherton, R.E.; Erdjument-Bromage, H.; Arribas, J.; Blackburn, R.K.; Weskamp, G.; Tempst, P.; Blobel, C.P.
Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity
J. Biol. Chem.
274
3531-3540
1999
Mus musculus
brenda
McCulloch, D.R.; Harvey, M.; Herington, A.C.
The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone
Mol. Cell. Endocrinol.
167
11-21
2000
Homo sapiens
brenda
Schwettmann, L.; Tschesche, H.
Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin
Protein Expr. Purif.
21
65-70
2001
Homo sapiens
brenda
Mahimkar, R.M.; Visaya, O.; Pollock, A.S.; Lovett, D.H.
The disintegrin domain of ADAM9: a ligand for multiple b1 renal integrins
Biochem. J.
385
461-468
2005
Mus musculus
brenda
Karadag, A.; Zhou, M.; Croucher, P.I.
ADAM-9 (MDC-9/meltrin-gamma), a member of the a disintegrin and metalloproteinase family, regulates myeloma-cell-induced interleukin-6 production in osteoblasts by direct interaction with the alpha(v)beta5 integrin
Blood
107
3271-3278
2006
Homo sapiens
brenda
Shintani, Y.; Higashiyama, S.; Ohta, M.; Hirabayashi, H.; Yamamoto, S.; Yoshimasu, T.; Matsuda, H.; Matsuura, N.
Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis
Cancer Res.
64
4190-4196
2004
Homo sapiens, Mus musculus
brenda
Mazzocca, A.; Coppari, R.; De Franco, R.; Cho, J.; Libermann, T.A.; Pinzani, M.; Toker, A.
A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions
Cancer Res.
65
4728-4738
2005
Homo sapiens
brenda
Peduto, L.; Reuter, V.E.; Shaffer, D.R.; Scher, H.I.; Blobel, C.P.
Critical function for ADAM9 in mouse prostate cancer
Cancer Res.
65
9312-9319
2005
Mus musculus
brenda
Sung, S.; Kubo, H.; Shigemura, K.; Arnold, R.S.; Logani, S.; Wang, R.; Konaka, H.; Nakagawa, M.; Mousses, S.; Amin, M.; Anderson, C.; Johnstone, P.; Petros, J.A.; Marshall, F.F.; Zhau, H.E.; Chung, L.W.
Oxidative stress induces ADAM9 protein expression in human prostate cancer cells
Cancer Res.
66
9519-9526
2006
Homo sapiens
brenda
Asayesh, A.; Alanentalo, T.; Khoo, N.K.; Ahlgren, U.
Developmental expression of metalloproteases ADAM 9, 10, and 17 becomes restricted to divergent pancreatic compartments
Dev. Dyn.
232
1105-1114
2005
Mus musculus
brenda
Hirao, T.; Nanba, D.; Tanaka, M.; Ishiguro, H.; Kinugasa, Y.; Doki, Y.; Yano, M.; Matsuura, N.; Monden, M.; Higashiyama, S.
Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells
Exp. Cell Res.
312
331-339
2006
Mus musculus
brenda
Zigrino, P.; Mauch, C.; Fox, J.W.; Nischt, R.
Adam-9 expression and regulation in human skin melanoma and melanoma cell lines
Int. J. Cancer
116
853-859
2005
Homo sapiens
brenda
Carl-McGrath, S.; Lendeckel, U.; Ebert, M.; Roessner, A.; Roecken, C.
The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer
Int. J. Oncol.
26
17-24
2005
Homo sapiens
brenda
Yamada, D.; Ohuchida, K.; Mizumoto, K.; Ohhashi, S.; Yu, J.; Egami, T.; Fujita, H.; Nagai, E.; Tanaka, M.
Increased expression of ADAM 9 and ADAM 15 mRNA in pancreatic cancer
Anticancer Res.
27
793-799
2007
Homo sapiens
brenda
Deuss, M.; Reiss, K.; Hartmann, D.
Part-time alpha-secretases: the functional biology of ADAM 9, 10 and 17
Curr. Alzheimer Res.
5
187-201
2008
Mus musculus
brenda
Zigrino, P.; Steiger, J.; Fox, J.W.; Loeffek, S.; Schild, A.; Nischt, R.; Mauch, C.
Role of ADAM-9 disintegrin-cysteine-rich domains in human keratinocyte migration
J. Biol. Chem.
282
30785-30793
2007
Homo sapiens
brenda
Ma, G.F.; Liljestroem, M.; Ainola, M.; Chen, T.; Tiainen, V.M.; Lappalainen, R.; Konttinen, Y.T.; Salo, J.
Expression of ADAM9 (meltrin-gamma) around aseptically loosened total hip replacement implants
Rheumatology
45
808-814
2006
Homo sapiens
brenda
Parry, D.A.; Toomes, C.; Bida, L.; Danciger, M.; Towns, K.V.; McKibbin, M.; Jacobson, S.G.; Logan, C.V.; Ali, M.; Bond, J.; Chance, R.; Swendeman, S.; Daniele, L.L.; Springell, K.; Adams, M.; Johnson, C.A.; Booth, A.P.; Jafri, H.; Rashid, Y.; Banin, E.; Strom, T.M.; Farber, D.B.; Sharon, D.; Blobel, C.P.; Pugh, E.
Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice
Am. J. Hum. Genet.
84
683-691
2009
Homo sapiens, Mus musculus
brenda
Oksala, N.; Levula, M.; Airla, N.; Pelto-Huikko, M.; Ortiz, R.M.; Jaervinen, O.; Salenius, J.P.; Ozsait, B.; Komurcu-Bayrak, E.; Erginel-Unaltuna, N.; Huovila, A.P.; Kytoemaeki, L.; Soini, J.T.; Kaehoenen, M.; Karhunen, P.J.; Laaksonen, R.; Lehtimaeki, T.
ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries--Tampere vascular study
Ann. Med.
41
279-290
2009
Homo sapiens
brenda
Zubel, A.; Flechtenmacher, C.; Edler, L.; Alonso, A.
Expression of ADAM9 in CIN3 lesions and squamous cell carcinomas of the cervix
Gynecol. Oncol.
114
332-336
2009
Homo sapiens
brenda
Kropatsch, R.; Petrasch-Parwez, E.; Seelow, D.; Schlichting, A.; Gerding, W.M.; Akkad, D.A.; Epplen, J.T.; Dekomien, G.
Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene
Mol. Cell. Probes
24
357-263
2010
Canis lupus familiaris (E7AIM5), Canis lupus familiaris
brenda
Cong, L.; Jia, J.
Promoter polymorphisms which regulate ADAM9 transcription are protective against sporadic Alzheimers disease
Neurobiol. Aging
32
54-62
2009
Homo sapiens
brenda
Mongaret, C.; Alexandre, J.; Thomas-Schoemann, A.; Bermudez, E.; Chereau, C.; Nicco, C.; Goldwasser, F.; Weill, B.; Batteux, F.; Lemare, F.
Tumor invasion induced by oxidative stress is dependent on membrane ADAM 9 protein and its secreted form
Int. J. Cancer
129
791-798
2011
Homo sapiens
brenda
Zigrino, P.; Nischt, R.; Mauch, C.
The disintegrin-like and cysteine-rich domains of ADAM-9 mediate interactions between melanoma cells and fibroblasts
J. Biol. Chem.
286
6801-6807
2011
Homo sapiens
brenda
Abety, A.N.; Fox, J.W.; Schoenefuss, A.; Zamek, J.; Landsberg, J.; Krieg, T.; Blobel, C.; Mauch, C.; Zigrino, P.
Stromal fibroblast-specific expression of ADAM-9 modulates proliferation and apoptosis in melanoma cells in vitro and in vivo
J. Invest. Dermatol.
132
2451-2458
2012
Mus musculus (Q61072), Mus musculus
brenda
Wang, X.; Polverino, F.; Rojas-Quintero, J.; Zhang, D.; Sánchez, J.; Yambayev, I.; Lindqvist, E.; Virtala, R.; Djukanovic, R.; Davies, D.; Wilson, S.; ODonnell, R.; Cunoosamy, D.; Hazon, P.; Higham, A.; Singh, D.; Olsson, H.; Owen, C.
A disintegrin and metalloproteinase domain-9 A novel proteinase culprit with multifarious contributions to chronic obstructive pulmonary disease
Am. J. Respir. Crit. Care Med.
198
1500-1518
2018
Mus musculus, Homo sapiens (Q13443)
-
brenda
English, W.; Siviter, R.; Hansen, M.; Murphy, G.
ADAM9 is present at endothelial cell - cell junctions and regulates monocyte - endothelial transmigration
Biochem. Biophys. Res. Commun.
493
1057-1062
2017
Mus musculus (Q61072)
brenda
Maretzky, T.; Swendeman, S.; Mogollon, E.; Weskamp, G.; Sahin, U.; Reiss, K.; Blobel, C.
Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays
Biochem. J.
474
1469-1479
2017
Mus musculus (Q61072)
brenda
Baggen, J.; Jan Thibaut, H.; Hurdiss, D.; Wahedi, M.; Van Vliet, A.; Van Kuppeveld, F.
Identification of the cell-surface protease adam9 as an entry factor for encephalomyocarditis virus
mBio
10
e1780
2019
Homo sapiens (Q13443), Homo sapiens
brenda
Wang, J.; Zhou, Y.; Fei, X.; Chen, X.; Yan, J.; Liu, B.; Zhu, Z.
ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126
Oncol. Rep.
37
2033-2040
2017
Homo sapiens (Q13443)
brenda
Chiu, K.; Kuo, T.; Kuok, Q.; Lin, Y.; Hua, C.; Lin, C.; Su, P.; Lai, L.; Sher, Y.
ADAM9 enhances CDCP1 protein expression by suppressing MIR-218 for lung tumor metastasis
Sci. Rep.
5
16426
2015
Homo sapiens (Q13443), Homo sapiens
brenda
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