3.4.21.B7: mannan-binding lectin-associated serine protease 1
This is an abbreviated version!
For detailed information about mannan-binding lectin-associated serine protease 1, go to the full flat file.
Word Map on EC 3.4.21.B7
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3.4.21.B7
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masp-3
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silk
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spider
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ficolins
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dragline
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c1s
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ampullate
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spidroins
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convertase
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collagen-like
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clavipes
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collectins
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m-ficolin
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autoactivation
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nephila
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subcomponents
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complement-activating
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c1-inhibitor
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latrodectus
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pattern-recognition
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widow
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fibrinogen-like
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protease-2
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opsonin
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extensibility
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urochord
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c1-inh
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hesperus
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medicine
- 3.4.21.B7
- masp-3
-
silk
- spider
- ficolins
-
dragline
- c1s
-
ampullate
-
spidroins
-
convertase
-
collagen-like
- clavipes
-
collectins
- m-ficolin
-
autoactivation
- nephila
-
subcomponents
-
complement-activating
- c1-inhibitor
- latrodectus
-
pattern-recognition
- widow
-
fibrinogen-like
-
protease-2
-
opsonin
-
extensibility
-
urochord
-
c1-inh
- hesperus
- medicine
Reaction
endopeptidase activity. It triggers the activation of complement cascade by activating the C4 and C2 components. It activates the C4 component by cleaving the alpha-chain of C4 =
Synonyms
mannan-binding lectin-associated serine protease, mannan-binding lectin-associated serine protease-1, mannose-binding lectin-associated serine protease, MASP-1, MASP1, MBL-associated serine protease, MBL-associated serine protease 1, MBL-associated serine protease-1, MBL-MASP, P100, Ra-reactive factor, RaRF, S01.198
ECTree
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General Information
General Information on EC 3.4.21.B7 - mannan-binding lectin-associated serine protease 1
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malfunction
metabolism
physiological function
additional information
enzyme-deficient mice lack alternative pathway activation because factor D remains as a proenzyme in the serum
malfunction
increased MASP-1 plasma levels in patients in the suba-cute phase of myocardial infarction, but decreased levels of MASP-1 in patients withacute ischemic stroke
malfunction
N-terminal parts of MASP-1 enzyme which only contain non-enzymatic domains, and a stable zymogen mutant form of enzyme MASP-1 are ineffective to stimulate endothelial cells
malfunction
presence of a functional alternative pathway in a human patient with Malpuech-Michels-Mingarelli-Carnevale (3MC) syndrome caused by a genetic defect in the MASP1 gene, which abolishes the production of all three splice products of this gene: mannan-binding lectin-associated serine proteases 1 and 3, and MBL-associated protein of 44 kDa, a human complement
among the components of the mannose-binding lectinMASPs complexes only enzyme MASP-1 is able to trigger response in human umbilical vein endothelial cells and the proteolytic activity of MASP-1 is essential
metabolism
both MASP-1 and MASP-2 are essential for lectin pathway activation in normal human serum
metabolism
human umbilical vein endothelial cells, activated by recombinnat MASP-1, secrete interleukin-6 and interleukin-8, but not interleukin-1alpha, interleukin-1ra, TNFalpha and MCP-1. rMASP-1 induces interleukin-6 and interleukin-8 production with different kinetics. Enzyme-triggered interleukin-6 and interleukin-8 production is regulated predominantly by the p38-MAPK pathway. The supernatant of rMASP-1-stimulated cells activates the chemotaxis of neutrophil granulocytes as an integrated effect of cytokine production
metabolism
influence of buffer composition on the activity of the alternative pathway of complement activation in mice in the presence and the absence of the Masp1 gene products: MASP-1, MASP-3, and MAp44
metabolism
target binding of pattern recognition molecules leads to the activation of zymogen mannan-binding lectin-associated serine proteases and triggers the lectin pathway, an antibody-independent activation route of the complement system, which provides immediate defense against pathogens and altered self-cells, but also causes severe tissue damage after stroke, heart attack, and other ischemia reperfusion injuries. MASP-2 and MASP-1 are both essential pathway components
metabolism
the enzyme is associated with humoral pattern-recognition molecules, overview
metabolism
the enzyme is part of the lectin pathway complement cascade, that is part of the innate immune system responsible for the initiation of inflammation and elimination of invading foreign cells
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MASP-1 does not require binding to mannose binding lectin-A, mannose binding lectin-C, or ficolin-A to activate the alternative pathway of complement
physiological function
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the bradykinin production by MASP-1 may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in hereditary angioedema patients
physiological function
besides playing a crucial role in complement activation, the enzyme also triggers other cascade systems and even cells to mount a more powerful innate immune response, multiple roles of MASP-1 in the initiation of the innate immune response, overview. Enzyme MASP-1 is the one responsible for triggering the lectin pathway via its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. MASP-1 interacts with the coagulation cascade and the kinin generating system, and it can also activate endothelial cells eliciting pro-inflammatory signaling. MASP-1 seems to be a major link between the complementsystem and coagulation. Role of MASP-1 in endothelial cell activation and blood coagulation, and role of the enzyme in cardiovascular diseases, detailed overview
physiological function
enzyme MASP-1 plays a central role in the early innate immune response. The initiation complexes of the lectin pathway, consisting of mannose-binding lectin and associated serine proteases (MASPs) elicit Ca2+-signaling in cultured endothelial cells. The recombinant catalytic fragment of MASP-1 activates endothelial cells by cleaving protease activated receptor 4. Mannose binding lectin-mannan-binding lectin-associated serine protease 1 complexes trigger intracellular Ca2+-signaling in human umbilical vein endothelial cells, overview
physiological function
mannan-binding lectin-associated serine proteases MASP-1 and MASP-2 can readily form heterodimers after dissociation and re-association, however, in the presence of Ca2+ exchange of subunits is slow between the homodimers. Modeling of isoforms MASP-1:MASP-3 heterodimer formation indicates that subunits of these proteins are readily exchanged even in the presence of Ca2+
physiological function
MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative complement system pathways
physiological function
MASP-1 cleaves complement component C2 but not complement component C4 and therefore is not capable of generating C3 convertase alone
physiological function
MASP-1, the most abundant enzyme of the complement lectin pathway, can induce p38-MAPK activation, NFkappaB signaling, and Ca2+-mobilization in endothelial cells and induces a unique cytokine pattern in endothelial cells linking complement system and neutrophil granulocytes. Besides initializing the complement lectin pathway, MASP-1 may activate neutrophils indirectly, via the endothelial cells, which link these effective antimicrobial host defense mechanisms
physiological function
the addition of mannan-binding lectin or ficolins allows the formation of serine proteases MASP-1-MASP-2 co-complexes. Co-complexes have a functional role in activating complement and are present in serum at varying levels, impacting on the degree of complement activation. Coexpression of MASP-2 with MASP-1, MASP-3, or mannan-binding lectin-associated protein 4 leads to detectable levels of heterodimers
physiological function
the enzyme MASP-1 is part of the lectin pathway of the complement system and is able to induce and promote clot formation, MASP-1-induced clotting is dependent on prothrombin
physiological function
the mannose-binding lectin-associated serine protease-1 is a significant contributor to coagulation in a murine model of occlusive thrombosis, it plays a key role in thrombus formation in vitro and in vivo. Whole blood aggregation demonstrated increased mannose-binding lectin-mannose-binding lectin-associated serine protease complex-dependent platelet aggregation
physiological function
the pro-factor D cleaving activity of MASP-1/-3 is not required for alternative pathway function, overview
physiological function
the pro-factor D cleaving activity of MASP-1/-3 is not required for alternative pathway function, overview. In humans, neither MASP-1 nor MASP-3 are required for alternative pathway function, overview
physiological function
addition of recombinant active MASP-1 to a a microvascular, whole blood flow model results in accelerated fibrin clot formation while addition of inhibitor SGMI-1 delays it. MASP-1 inhibition and especially inhibition of both lectin pathway and complement pathway significantly diminishes fibrin deposition upon complement activation
physiological function
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in cells over-expressing gcMASP-1, transcript levels of almost all immune components, except gcMBL and gcC5, are significantly enhanced, and gcIL1beta, gcTNF-alpha, gcIFN, gcCD59, gcC5aR1, and gcITGb-2 are significantly upregulated after exposure to Aeromonas hydrophila. MASP-1 interference downregulates the transcript levels after Aeromonas hydrophila challenge. In addition, gcMASP-1 activates NF-kappaB signaling
physiological function
MASP-1 is not an activator of complement factor D precursor
physiological function
recombinant expression of MASP-1 in HUVECs decreases the expression of ICAM-2 and increases that of E-selectin, whereas ICAM-1, VCAM-1 and P-selectin expression remain unchanged. These changes result in increased adherence between differentiated PLB-985 cells and endothelial cells. Complement MASP-1 can increase adhesion between neutrophils and endothelial cells ina direct fashion
enzyme MASP-1 shows a more relaxed substrate specificity compared to the related complement enzymes, crystal structure analysis, overview. The catalytic triad of zymogen MASP-1 is in an active-like conformation, while the S1 pocket is blocked and the oxyanion hole is distorted, which are typical features of zymogen serine proteases. Upon activation, the new amino-terminus forms a salt-bridge with Asp645 rearranging the surface loopsand allowing the oxyanion hole and the S1 pocket to form. In the structure of zymogen MASP-1 two positive side chains might be able to substitute for the amino-terminus aiding Aspc194to rotateto the active-like position
additional information
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enzyme MASP-1 shows a more relaxed substrate specificity compared to the related complement enzymes, crystal structure analysis, overview. The catalytic triad of zymogen MASP-1 is in an active-like conformation, while the S1 pocket is blocked and the oxyanion hole is distorted, which are typical features of zymogen serine proteases. Upon activation, the new amino-terminus forms a salt-bridge with Asp645 rearranging the surface loopsand allowing the oxyanion hole and the S1 pocket to form. In the structure of zymogen MASP-1 two positive side chains might be able to substitute for the amino-terminus aiding Aspc194to rotateto the active-like position
additional information
the catalytic activity of MASP-1 suppresses its expression through intracellular rapid autoactivation and autodegradation
additional information
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the catalytic activity of MASP-1 suppresses its expression through intracellular rapid autoactivation and autodegradation