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Enzyme Nomenclature
Information on EC 3.4.24.18 - meprin A
for references in articles please use BRENDA:EC3.4.24.18
Word Map on EC 3.4.24.18
- 3.4.24.18
- renal
- metalloendopeptidase
- astacins
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brush
- metalloproteases
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natriuretic
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math
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brush-border
- actinonin
- phosphoramidon
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azocasein
- enkephalinase
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astacin-like
- microvillar
- thiorphan
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metzincins
- sheddase
- medicine
- pharmacology
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
3.4.24.18
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RECOMMENDED NAME
GeneOntology No.
meprin A
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of protein and peptide substrates preferentially on carboxyl side of hydrophobic residues
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of arylamide bond
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hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
148938-24-3
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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667471, 685446, 687981, 688204, 707623, 710819, 717227, 717474, 733064, 733519, 734259, 734296, 734332, 734610
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31018, 31019, 31022, 31026, 31028, 31030, 669250, 685446, 696035, 711053, 713492, 733064, 733065, 733066, 733288, 733947, 734296, 734610, 735169
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db/db mice lacking the hypothalamic leptin receptor, representing a model of type 2 diabetes mellitus
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treated with streptozocin, representing a model of type 1 diabetes mellitus
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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homology modeling of the protease domain of meprin alpha on the astacin crystal structure and molecular dynamics simulation study, overview
evolution
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meprin A, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases
evolution
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meprin A, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases
evolution
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meprin A, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases
evolution
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meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily
evolution
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meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily. Meprins belong to the astacin family of metalloproteases, comprising only six members in humans. These enzymes are characterized by a conserved zinc-binding motif (HExxHxxGxxHxxxRxDR) and by a sequence in close proximity to the active-site cleft, the so called Met-turn, that includes a tyrosine residue as a fifth zinc ligand. Within the astacin family, meprins exhibit a unique domain composition
evolution
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meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily
evolution
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meprin alpha is a metalloprotease of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR). Human meprin-alpha and -beta protease, EC 3.4.24.63, subunits are 55% identical at the amino acid level, while the substrate and peptide bond specificities vary markedly
evolution
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meprin A, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases
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malfunction
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meprin inhibition elevates levels of natriuretic peptides in plasma and the vascular wall, decreases plaque volume and suppresses lipid deposition in carotid arteries, reduces production of reactive oxygen species and apoptosis (which are associated with atherosclerosis) in the vascular wall, and increases natriuretic peptide function on cell apoptosis, proliferation, and intracellular reactive oxygen species generation in the THP-1 cell line and primary vascular smooth muscle cells
malfunction
knockdown of meprin alpah1 mRNA causes defects in general tissue differentiation; meprin alpha2 morphants show severe failures in the formation of the vascular system
malfunction
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breast cancer MDA-MB-435 cells treated with the meprin inhibitor actinonin are less invasive in vitro. Altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
malfunction
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altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
malfunction
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altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
malfunction
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monocytes from meprin knockout mice on a C57BL/6 background are less able to migrate through an MDCK cell monolayer than monocytes from their wild-type counterparts
malfunction
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the knockdown of meprin beta in zebrafish embryos leads to a general failure in organogenesis, resulting in the death of the embryos between days 1 and 3 postfertilization
malfunction
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mice lacking meprin alpha and meprin beta are significantly protected against renal ischaemia/reperfusion injury and bladder inflammation. Meprin alpha-knockout mice exhibit less renal damage compared with wild-type mice
malfunction
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enzyme downregulation causes impaired intestinal mucin release and barrier function,and decreases tensile strength in the skin, but it also leads to protection against sepsis and renal injury. Enzyme upregulation can cause fibrosis, pulmonary hypertension, the Kawasaki syndrome, inflammatory bowel disease, and is involved in nephritis, cancer, and Alzheimer's disease, overview
malfunction
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meprin alpha knock-out mice exhibit decreased collagen deposition in skin resulting in impaired tensile strength, overview. Overexpression of meprin metalloproteases occurs under fibrotic conditions in the skin (keloids) and the lung (pulmonary hypertension)
malfunction
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enzyme-deficient mice show lower amounts of mature collagen I compared with wild-type mice and exhibit significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength
malfunction
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monocytes from meprin knockout mice on a C57BL/6 background are less able to migrate through an MDCK cell monolayer than monocytes from their wild-type counterparts
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malfunction
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altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
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metabolism
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following ischemia-reperfusion- and cisplatin-induced acute kidney injury, meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine
metabolism
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following ischemia-reperfusion- and cisplatin-induced acute kidney injury, meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine
metabolism
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following ischemia-reperfusion- and cisplatin-induced acute kidney injury, meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine
metabolism
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meprin A is more effective than meprin B, EC 3.4.24.63, in impairing MDCK epithelial barrier function
metabolism
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role of interaction of mannan-binding protein with meprins at the initial step of complement activation in ischemia/reperfusion injury to mouse kidney. Co-localization of the enzyme with serum-type mannan-binding protein and C3b on both the cortex and the medulla in the renal I/R-operated mouse kidney
metabolism
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meprins show higher substrate and cleavage specificity compared to matrix metalloproteases
metabolism
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meprins show higher substrate and cleavage specificity compared to matrix metalloproteases
metabolism
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meprin A is more effective than meprin B, EC 3.4.24.63, in impairing MDCK epithelial barrier function
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metabolism
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role of interaction of mannan-binding protein with meprins at the initial step of complement activation in ischemia/reperfusion injury to mouse kidney. Co-localization of the enzyme with serum-type mannan-binding protein and C3b on both the cortex and the medulla in the renal I/R-operated mouse kidney
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metabolism
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following ischemia-reperfusion- and cisplatin-induced acute kidney injury, meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine
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physiological function
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meprin beta induces a dramatic change in cell morphology and a significant reduction in cell number, whereas meprin alpha plays a role for basal keratinocyte proliferation in vitro
physiological function
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meprin A plays a role in the regulation of B-type natriuretic peptide 1-32 bioactivity in the kidney
physiological function
meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Meprins play a significant role in VEGF-A processing, subsequently regulating angiogenesis; meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Meprins play a significant role in VEGF-A processing, subsequently regulating angiogenesis
physiological function
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meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Meprins play a significant role in vascular endothelial growth factor-A processing, subsequently regulating angiogenesis
physiological function
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meprin-alpha is capable of increasing lipopolysaccharide-induced production of cytokines in peripheral blood mononuclear cells, which is associated with the activation of nuclear factor-kappaB
physiological function
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meprins stimulate epithelial Na+ channel (ENaC) expressed exogenously in Xenopus oocytes and endogenously in epithelial cells. Co-expression of ENaC subunits and meprin beta or alpha/beta in Xenopus oocytes increases amiloride-sensitive Na+ currents 2fold. The meprin-mediated increase in ENaC currents in oocytes and epithelial cell monolayers requires meprin beta, but not the alpha subunit
physiological function
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the enzyme is involved in the progression of colon cancer, the ability of meprins to degrade extracellular matrix components is implicated in cell migration of leukocytes of mesenteric lymph nodes and invasion of tumor cells that express meprin
physiological function
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the activity of meprin A enables monocytes to migrate through an epithelial barrier more readily allowing inflammatory molecules such as cytokines and monocytes to gain access to sites of injury. Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin
physiological function
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the activity of meprin A enables monocytes to migrate through an epithelial barrier more readily allowing inflammatory molecules such as cytokines and monocytes to gain access to sites of injury. Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin
physiological function
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meprins may impact kidney injury, in part, via modulation of protein kinase A signaling pathways, meprins are implicated in ischemia-reperfusion-induced renal injury and diabetic nephropathy. Meprin cleavage decreases the kinase activity of protein kinase A subunits Calpha, Cbeta1, and Cbeta2
physiological function
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besides its contribution in the regulation of angiogenesis, meprin alpha is involved in cardiovascular homoeostasis by enzymatic cleavage of the 32-amino acid B-type natriuretic peptide in vitro and in vivo, leading to its reduced bioactivity. Procollagen III is processed to its mature form by meprin alpha and meprin beta, an essential step in collagen fibril assembly. The metalloprotease meprin alpha is involved in inflammation, neurodegeneration, cancer and fibrosis, overview. Gene MEP1A is genetically associated with inflammatory bowel disease, on the basis of single nucleotide polymorphisms in ulcerative colitis patients. Meprin alpha induces inflammation by transactivation of the EGF receptor through the release of its ligands transforming growth factor alpha and EGF from the cell surface, meprin alpha is able to release soluble EGF and TGFalpha, consequently activating the EGFR and ERK1/2 (extracellular-signal-regulated kinase 1/2) signalling cascade in a ligand-dependent manner. Meprin alpha expressed in basal epidermis promotes cell proliferation
physiological function
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the metalloproteases meprin alpha and meprin beta are involved in inflammation, neurodegeneration, cancer and fibrosis, overview
physiological function
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serum-type mannan-binding protein interacts with meprins in vivo in the I/R-operated mouse kidney and initiates the complement activation through the interaction with meprins in vitro, overview
physiological function
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the enzyme is involved in inflammation by the release and maturation of cytokines and proteoglycans, it induces extracellular matrix assembly and fibrosis, and enhances cancer progression through transactivation of epidermal growth factor receptors. The cleavage of fibrillar procollagen by the enzyme is required and sufficient to induce collagen fibril assembly
physiological function
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the enzyme is involved in inflammation by the release and maturation of cytokines and proteoglycans, it induces extracellular matrix assembly and fibrosis, and enhances cancer progression through transactivation of epidermal growth factor receptors. The cleavage of fibrillar procollagen by the enzyme is required and sufficient to induce collagen fibril assembly
physiological function
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physiological relevance of the unique ability of meprin alpha and meprin beta, EC 3.4.24.63, to remove the both the C- and N-propeptides of type I procollagen, subsequently releasing fibril-forming mature collagen molecules. The enzyme contributes to the integrity of connective tissue in skin
physiological function
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the activity of meprin A enables monocytes to migrate through an epithelial barrier more readily allowing inflammatory molecules such as cytokines and monocytes to gain access to sites of injury. Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin
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physiological function
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serum-type mannan-binding protein interacts with meprins in vivo in the I/R-operated mouse kidney and initiates the complement activation through the interaction with meprins in vitro, overview
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physiological function
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the activity of meprin A enables monocytes to migrate through an epithelial barrier more readily allowing inflammatory molecules such as cytokines and monocytes to gain access to sites of injury. Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin
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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
2-aminobenzoic acid-RPPGFSPFRK(2,4-dinitrophenyl)G-OH + H2O
?
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?
2-aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Gly-Pro-Phe + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Hyp-Gly-Phe + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Ala + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Glu + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Leu + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly + Lys-Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Ile-Phe + Ser-Pro-(4-nitro)Phe-Arg
2-aminobenzoyl-RPPGFSPFRK-(dinitrophenyl)-G + H2O
?
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fluorogenic bradykinin analog substrate
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?
annexin A1 + H2O
?
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substrate identified by 2D IEF/SDS-PAGE-based image analysis
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?
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ala-Pro-Phe-Arg
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Arg-Pro-Phe-Arg
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Lys-Pro-Phe-Arg
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Phe-Pro-Phe-Arg
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ser-Pro-Phe-Arg
B-type natriuretic peptide 1-32 + H2O
B-type natriuretic peptide 8-32 + Ser-Pro-Lys-Met-Val-Gln-Gly
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?
Benzyloxycarbonyl-Glu-Lys-Lys 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 9.1% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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Benzyloxycarbonyl-Val-Leu-Lys 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 10.4% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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collagen type V + H2O
?
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substrate identified by 2D IEF/SDS-PAGE-based image analysis
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?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
gastri-releasing peptide-(14-27) + H2O
?
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peptide of the gastrointestinal tract
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?
Glutaryl-Phe 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 2.4% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 6.2% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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Luliberin + H2O
?
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i.e. luteinizing-hormone releasing hormone, preferred cleavage site: Trp3-Ser4, other sites are Ser4-Tyr5 and Tyr5-Gly6
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luteinizing hormone releasing hormone LHRH + H2O
?
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peptide of the gastrointestinal tract
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?
lysyl oxidase + H2O
?
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substrate identified by 2D IEF/SDS-PAGE-based image analysis
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?
Parathyroid hormone + H2O
Hydrolyzed parathyroid hormone
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i.e. hPTH-(1-84), in vivo and in vitro
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pro-interleukin 1beta + H2O
interleukin 1beta + H2O
cleavage at the H115-D116 bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin beta site. Both oligomeric meprin A and recombinant meprin alpha are capable of cleaving
the biological activity of the pro-interleukin-1beta cleaved product produced by meprin A, is 3fold higher to that of the interleukin-1beta product produced by meprin b or caspase-1
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?
pro-KLK7 + H2O
KLK7 + ?
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meprin beta cleaves pro-KLK7 between Gly17 and Asp18
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?
protein kinase A + H2O
?
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the enzyme cleaves at defined sites, isoform-specific interactions between the catalytic subunit of PKA (PKA C) and meprins, overview
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?
protein kinase A catalytic subunit Cbeta1 + H2O
?
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the enzyme cleaves at defined sites, cytosolic-enriched kidney proteins from meprin alphabeta double knockout mice, and purified forms of recombinant mouse PKA Calpha, Cbeta1, and Cbeta2, are incubated with activated forms of either homomeric meprinA or meprin B, EC 3.4.24.63, product analysis by mass spectrometry, overview. Meprin A only cleaves PKA Cbeta1
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-
?
Succinyl-Ala-Ala-Pro-Phe 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 9% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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Succinyl-Ala-Pro-Ala 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 2.8% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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-
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Succinyl-Gly-Pro 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 10.7% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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-
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Succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 5.6% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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tissue growth factor-alpha + H2O
?
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meprin alpha can process tissue growth factor-alpha
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?
Tyr 4-methylcoumarin 7-amide + H2O
?
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poor substrate, hydrolysis at 3.3% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
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-
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VEGF-A + H2O
?
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human meprin alpha cleaves VEGF-A in vitro, generating proteolytic fragments as found in wild-type zebrafish
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-
?
vinculin + H2O
?
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substrate identified by 2D IEF/SDS-PAGE-based image analysis
-
-
?
2-aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Gly-Pro-Phe + Ser-Pro-(4-nitro)Phe-Arg
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fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Gly-Pro-Phe + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Hyp-Gly-Phe + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Hyp-Gly-Phe + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Ala + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Ala-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Ala + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Ala-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Glu + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Glu-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Glu + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage site: Glu-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Leu + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage sites: Leu-Ser (major site) and Gly-Leu
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Leu + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage sites: Leu-Ser (major site) and Gly-Leu
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly + Lys-Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage sites: Gly-Lys (major site) and Lys-Ser
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly + Lys-Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrate, cleavage sites: Gly-Lys (major site) and Lys-Ser
major products
-
2-aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Ile-Phe + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrates, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Ile-Phe + Ser-Pro-(4-nitro)Phe-Arg
-
fluorogenic bradykinin analog substrates, cleavage site: Phe-Ser
-
-
alpha-melanocyte stimulating hormone + H2O
?
-
i.e. acetyl-Ser-Tyr-Ser-Met-Gly-His-Phe-Arg-Trp-Gly-Lys-Pro-Val, cleavage sites: Ser-Met, Gly-Lys, mouse
-
-
-
alpha-melanocyte stimulating hormone + H2O
?
-
peptide of the gastrointestinal tract
-
?
alpha-melanocyte-stimulating hormone + H2O
?
-
human homomeric recombinant enzyme
-
-
?
alpha-melanocyte-stimulating hormone + H2O
?
-
murine homomeric recombinant enzyme
-
-
?
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
2 cleavage sites: Tyr-Ile and Phe-His
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
cleavage site: Tyr-Ile
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
poor substrate
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
cleavage site: Tyr-Ile
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
poor substrate
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
poor substrate
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ala-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ala-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Arg-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Arg-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Lys-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Lys-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Phe-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Phe-Pro-Phe-Arg
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ser-Pro-Phe-Arg
-
i.e. nitrobradykinin, chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ser-Pro-Phe-Arg
-
i.e. nitrobradykinin, chromogenic bradykinin analog
-
-
azocasein + H2O
fragments of azocasein
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
azocasein + H2O
fragments of azocasein
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
azocasein + H2O
fragments of azocasein
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
azocasein + H2O
fragments of azocasein
-
better substrate for mouse enzyme than for rat enzyme
-
-
-
azocasein + H2O
fragments of azocasein
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
azocasein + H2O
fragments of azocasein
-
better substrate for mouse enzyme than for rat enzyme
-
-
-
B-type natriuretic peptide + H2O
?
-
meprin A degrades rat BNP but not human BNP
-
-
?
benzoyl-Gly-His-Leu + H2O
?
-
very poor substrate, t1/2 of more than 16 h
-
-
-
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
?
-
poor substrate, hydrolysis at 8.2% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
?
-
poor substrate, hydrolysis at 8.2% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
-
poor substrate, hydrolysis at 3.6% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
-
poor substrate, hydrolysis at 3.6% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
i.e. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, bradykinin(1-7) and bradykinin(1-8) best substrates next to substance P
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
one cleavage site: Phe-Ser
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
one cleavage site: Phe-Ser
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
one cleavage site: Phe-Ser (major cleavage site)
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
one cleavage site: Phe-Ser
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
-
minor cleavage site: Gly-Phe
-
-
-
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
Fibronectin + H2O
?
-
cleavage at positions Y294-Q295, N709-T210 and in the linker regions between fibronectin type I repeats 5 and 6 and fibronectin type II repeats 1 and 2
-
-
?
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
7 major and 3 minor sites
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
7 major and 3 minor sites
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
the others are Leu6-Cys(SO3-)7, Ala14-Leu15, Gly8-Ser9, His10-Leu11, Leu15-Tyr16, His5-Leu6 and Leu17-Val18
13 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
10 cleavage sites
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
7 major and 3 minor sites
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
oxidized form
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
oxidized form
13 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
10 cleavage sites
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
oxidized form
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
I125-iodinated
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
7 major and 3 minor sites
-
-
-
interleukin-6 + H2O
?
-
recombinant human substrate expressed in eukaryotic B9 cell line, inactivation. Human meprin A cleaves 20% of human interleukin-6 of about 22 kDa to a smaller product of about 21 kDa within 2 h. Meprin A cleaves human interleukin-6 at its C-terminus, fragmentation pattern, overview
-
-
?
interleukin-6 + H2O
?
-
recombinant human substrate expressed in an eukaryotic cell line, inactivation
-
-
?
interleukin-6 + H2O
?
-
recombinant murine substrate expressed in Escherichia coli, inactivation. The enzyme cleaves 90% of the substrate within 2 h, approximately 50 and 15% of the mIL-6 signal remain after 0.5 and 1 h of incubation with mouse meprin A, fragmentation pattern, overview
-
-
?
interleukin-6 + H2O
?
-
recombinant human substrate expressed in an eukaryotic cell line, inactivation
-
-
?
interleukin-6 + H2O
?
-
recombinant murine substrate expressed in Escherichia coli, inactivation. The enzyme cleaves 90% of the substrate within 2 h, approximately 50 and 15% of the mIL-6 signal remain after 0.5 and 1 h of incubation with mouse meprin A, fragmentation pattern, overview
-
-
?
luteinizing-hormone-releasing hormone + H2O
?
-
human homomeric recombinant enzyme
-
-
?
luteinizing-hormone-releasing hormone + H2O
?
-
murine homomeric recombinant enzyme
-
-
?
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
i.e. PABA-peptide, rat, human, arylamidolysis
-
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
very poor substrate, t1/2 of more than 16 h
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
very poor substrate, t1/2 of more than 16 h
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
-
-
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
i.e. PABA-peptide, rat, human, arylamidolysis
-
-
-
neurotensin + H2O
?
-
i.e. pyro-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, mouse, rat, cleavage sites: Glu-Asn, Asn-Lys
-
-
-
neurotensin + H2O
?
-
i.e. pyro-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, mouse, rat, cleavage sites: Glu-Asn, Asn-Lys
-
-
-
occludin + H2O
?
-
recombinant MBP-conjugated human substrate and recombinant enzyme, cleavage products of extracellular loop 1 and loop 2 are determined by mass spectrometry, overview. The cleavage site is between Gly100 and Ser101 is on the first extracellular loop of occludin
-
-
?
occludin + H2O
?
-
recombinant MBP-conjugated human substrate and recombinant enzyme, cleavage products of extracellular loop 1 and loop 2 are determined by mass spectrometry, overview. The cleavage site is between Gly100 and Ser101 is on the first extracellular loop of occludin
-
-
?
occludin + H2O
?
-
recombinant substrate in micelles and recombinant enzyme, cleavage products of extracellular loop 1 and loop 2 are determined by mass spectrometry, overview. The cleavage site is between Gly100 and Ser101 is on the first extracellular loop of occludin
-
-
?
occludin + H2O
?
-
recombinant substrate in micelles and recombinant enzyme, cleavage products of extracellular loop 1 and loop 2 are determined by mass spectrometry, overview. The cleavage site is between Gly100 and Ser101 is on the first extracellular loop of occludin
-
-
?
Parathyroid hormone + H2O
?
-
involved in PTH-degradation in human kidney
-
-
-
Parathyroid hormone + H2O
?
-
murine homomeric recombinant enzyme
-
-
?
parathyroid hormone fragment 13-34 + H2O
?
-
peptide of the gastrointestinal tract
-
?
procollagen I + H2O
collagen I + propeptide of collagen III
-
meprin alpha removes both the C- and N-propeptides of type I procollagen, subsequently releasing fibril-forming mature collagen molecules. The C-terminal cleavage sites in the proalpha1(I) chain generated by the enzyme is identified as Ala1218/Asp1219, identical to the BMP-1 cleavage site, and also Arg1227/Asp1228, nine residues C-terminal to the BMP-1 cleavage site
-
-
?
procollagen I + H2O
collagen I + propeptide of collagen III
-
recombinant human substrate, generation of mature collagen molecules that spontaneously assemble into collagen fibrils
-
-
?
Substance P + H2O
Hydrolyzed substance P
-
cleavage sites: Glu6-Phe7, Phe7-Phe8, Phe8-Gly9
-
-
-
Tyr-Leu-Val-Cys(SO3-)-Gly-Glu-Arg-Gly + H2O
?
-
synthetic peptide derived from insulin B-chain
-
-
-
Tyr-Leu-Val-Cys(SO3-)-Gly-Glu-Arg-Gly + H2O
?
-
synthetic peptide derived from insulin B-chain
-
-
-
vascular endothelial growth factor-A + H2O
?
-
cleavage of the vascular endothelial growth factor-A monomer by meprin alpha yields in two distinct fragments of 19600 Da, the N-terminal cleavage site in human vascular endothelial growth factor-A165 is between Ala30 and Glu31 due to recombinant human meprin alpha activity
-
-
?
Vasoactive intestinal peptide + H2O
?
-
peptide of the gastrointestinal tract
-
?
additional information
?
-
-
2D IEF/SDS-PAGE-based image analysis procedure to analyse candidate substrates for meprin in a cell culture system-based approach and identification of meprin substrates with cleaved non-trypsin-generated N- and C-termini in peptide fragments upon LC-MS/MS analysis
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
-
-
-
additional information
?
-
-
poor substrates are compounds with 3 or less amino acids
-
-
-
additional information
?
-
-
dansyl-(D)-Ala-Gly-4-phenylalanylglycine, [Leu]-enkephalin, [Met]-enkephalin
-
-
-
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
-
-
-
additional information
?
-
-
dansyl-(D)-Ala-Gly-4-phenylalanylglycine, [Leu]-enkephalin, [Met]-enkephalin
-
-
-
additional information
?
-
-
poor substrates are compounds with 3 or less amino acids
-
-
-
additional information
?
-
-
little or no activity towards benzoylarginine 2-naphthylamide, benzoylglycylarginine, benzyloxycarbonyl-Glu-Tyr, acetyl-Phe 2-naphthylester
-
-
-
additional information
?
-
-
no hydrolysis of Leu 4-nitroanilide, benzoyl-Arg-4-nitroanilide, succinyl-Ala 4-nitroanilide, Arg 4-methylcoumarinin 7-amide, benzoyl-Phe-Val-Arg 4-methylcoumarin 7-amide, Gly-Gly-Phe-Leu, Tyr-Gly-Gly-Phe-Leu, Tyr-Gly-Gly-Phe-Met, Leu-Arg-Arg-Ala-Ser-Leu-Gly, Ala-Phe-Pro-Leu-Gly-Phe, benzoyl-Phe-Val-Arg
-
-
-
additional information
?
-
-
hydrolyzes peptides of at least 8 amino acids and prefers peptide bonds flanked by hydrophobic or neutral amino acid residues although hydrolysis is not limited to these bonds
-
-
-
additional information
?
-
-
orcokinin and gastrin 17 are no substrates
-
?
additional information
?
-
-
orcokinin, gastrin 17, peptide YY, kinetensin, [Lys8]-vasopressin, somatostatin, kassinin, oxytocin, and alpha-neurokinin are no substrates
-
?
additional information
?
-
-
cleaves growth factors, extracellular matrix proteins, and biological active peptides
-
?
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
-
-
-
additional information
?
-
-
insulin, [Arg8]-vasopressin, cytochrome c, ovalbumin, serum albumin
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
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
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
procollagen I + H2O
collagen I + propeptide of collagen III
-
meprin alpha removes both the C- and N-propeptides of type I procollagen, subsequently releasing fibril-forming mature collagen molecules. The C-terminal cleavage sites in the proalpha1(I) chain generated by the enzyme is identified as Ala1218/Asp1219, identical to the BMP-1 cleavage site, and also Arg1227/Asp1228, nine residues C-terminal to the BMP-1 cleavage site
-
-
?
protein kinase A + H2O
?
-
the enzyme cleaves at defined sites, isoform-specific interactions between the catalytic subunit of PKA (PKA C) and meprins, overview
-
-
?
tissue growth factor-alpha + H2O
?
-
meprin alpha can process tissue growth factor-alpha
-
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
-
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
Parathyroid hormone + H2O
?
-
involved in PTH-degradation in human kidney
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
cleaves growth factors, extracellular matrix proteins, and biological active peptides
-
?
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
no activity with claudin-4 in MDCK cells
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Calcium
Zinc
Zn2+
additional information
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); Ca2+ reactivates inactive apoenzyme; metalloendopeptidase
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; tightly bound, no addition of Ca2+ required
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); Ca2+ reactivates inactive apoenzyme; metalloendopeptidase
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); Ca2+ reactivates inactive apoenzyme; metalloendopeptidase
Zinc
-
metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zinc
-
1 mol zinc per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; tightly bound, no addition of Zn2+ required
Zinc
-
1 mol zinc per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zinc
-
metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zn2+
-
meprin alpha is a metalloprotease of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR)
additional information
-
considerable stimulation of azocasein hydrolysis at ionic strength values up to 0.15-0.2
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(N-Hydroxycarboxamido)-4-methylpentanoyl-L-alanyl-glycylamide
-
i.e. Zinkov inhibitor
3-[(E)-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl]diazenyl]-7-nitronaphthalene-1,5-disulfonic acid
-
competitive inhibition
N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide
-
-
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide
-
-
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
-
-
verapamil
-
verapamil at 1 mg/kg, i.v. can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats
actinonin
-
a hydroxamate derivate and naturally occurring compound produced in actinomycetes. Hydroxamate inhibitors chelate the zinc ion in the active site
actinonin
-
i.e. 3-[[1-[[2-(hydroxymethyl)-1-pyrolidinyl]carbonyl]-2-methylpropyl]carbamoyl]octano hydroxamic acid, strong, kinetics
actinonin
-
in a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum interleukin 1beta, meprin inhibitor actinonin significantly reduces levels of serum interleukin 1beta
actinonin
-
a hydroxamate derivate and naturally occurring compound produced in actinomycetes. Hydroxamate inhibitors chelate the zinc ion in the active site
actinonin
-
pre-ischemic treatment with actinonin at 10 or 30 mg/kg, i.v. dose-ependently attenuates the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats
EDTA
-
restored by divalent metal ions, Zn2+ being more effective than Ca2+ or Mg2+
Pro-Leu-Gly-hydroxamate
-
binding structure in S subsites, overview. A decrease in solvent accessibility values at specific residues upon inhibitor binding occurs. The S subsite of the enzyme interacts with residues at P site of the inhibitor
additional information
-
amastatin, bestatin, puromycin, N-tosyl-L-Phe chloromethyl ketone, monoclonal antibody HBB 3/716/36; iodoacetate; leupeptin; no inhibition by phosphoramidon; PMSF, pepstatin
-
additional information
-
inhibitors of elastase, aminopeptidase, serine, aspartic or cysteic proteases; no inhibition by phosphoramidon
-
additional information
-
3,4-dichloroisocoumarin; iodoacetate; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
additional information
-
inhibitor screening, overview. Poor inhibition by NF449, a suramin analogue
-
additional information
-
binding sites and binding structure of hydroxamic acid derivative inhibitors, molecular dynamics simulation study, overview
-
additional information
-
diisopropyl phosphofluoridate, p-hydroxymercuribenzoate, phenylmercurisulfonate, antipain, cystine, oxidized glutathione; iodoacetate; leupeptin; no inhibition by phosphoramidon; PMSF, pepstatin
-
additional information
-
iodoacetate; L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (i.e. E-64); no inhibition by phosphoramidon; soybean trypsin inhibitor
-
additional information
-
3,4-dichloroisocoumarin; iodoacetate; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
additional information
-
hippuryl-His-Leu, His-Leu, benzamidine; soybean trypsin inhibitor
-
additional information
-
leupeptin; L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (i.e. E-64); NEM, tissue inhibitor of metalloproteinases; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
additional information
-
3,4-dichloroisocoumarin; iodoacetate; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
alpha- and beta-tryptase, urokinase plasminogen activator, KLK2, KLK6, KLK7, and KLK11 do not activate meprin alpha and beta
-
additional information
-
contrary to meprin B only very little activation by trypsin treatment
-
additional information
-
no activation by organomercurials or trypsin treatment
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
gastrin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0732
orcokinin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0296
protein GRP
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
additional information
additional information
-
Michaelis-Menten enzyme kinetics, overview
-
0.0223
alpha-MSH
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.292
alpha-MSH
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.101
bradykinin
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.125
bradykinin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0565
LHRH
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
0.156
LHRH
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 for between 8-30 min
-
0.018
protein PTH12-34
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0672
protein PTH12-34
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0339
secretin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.111
secretin
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0306
Substance P
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0413
Substance P
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00053
DL-Pro-DL-Leu-Gly-NH2
-
pH and temperature not specified in the publication
0.0004
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
-
pH 7.5, 37°C
0.0022
N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide
-
pH and temperature not specified in the publication
0.0015
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide
-
pH and temperature not specified in the publication
0.0004
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
-
pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.067
3-[(E)-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl]diazenyl]-7-nitronaphthalene-1,5-disulfonic acid
Homo sapiens;
-
pH 7.5, 25°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2.9
additional information
additional information
-
4.6673 mg azocasein/min/mg (untreated enzyme), 7.2512 mg azocasein/min/mg (trypsin-treated enzyme)
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
additional information
additional information
-
marked microheterogeneity due to glycosylation with pIs in the range of 6-6.85
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in human epidermis, meprin alpha is expressed exclusively in the keratinocytes of the stratum basale
-
in human epidermis, meprin beta is restricted to the cells of the stratum granulosum
additional information
-
in human epidermis, meprin alpha is expressed exclusively in the keratinocytes of the stratum basale, whereas meprin beta is restricted to the cells of the stratum granulosum