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Information on EC 3.4.21.104 - mannan-binding lectin-associated serine protease-2 and Organism(s) Rattus norvegicus and UniProt Accession Q9JJS8
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3.4.21.104 mannan-binding lectin-associated serine protease-2Specify your search results
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- 3.4.21.104
-
masps
- spider
-
silk
- ficolins
-
ampullate
-
dragline
-
spidroins
- c1s
- clavipes
- nephila
-
collectins
- m-ficolin
- widow
- hesperus
- latrodectus
- medicine
- molecular biology
- diagnostics
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Selective cleavage after Arg223 in complement component C2 (-Ser-Leu-Gly-Arg-/-Lys-Ile-Gln-Ile) and after Arg76 in complement component C4 (-Gly-Leu-Gln-Arg-/-Ala-Leu-Glu-Ile)
Synonyms
masp2, map19, mbl-associated serine protease 2, mannan-binding lectin-associated serine protease-2, mbp-associated serine protease, ccp1-ccp2-sp, mannan-binding lectin-associated serine protease 2, mannose-binding lectin-associated serine protease-2, mannose-binding lectin-associated serine protease 2, mannan-binding lectin associated serine protease-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
MASP-2A
-
catalytically inactive form in which the active site serine at position 613 has been replaced by alanine
MASP-2K
-
catalytically active form in which the arginine residue at the cleavage site for zymogen activation (Arg424) has been changed to a lysine residue to slow down the rate of spontaneous autoactivation during biosynthesis
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Selective cleavage after Arg223 in complement component C2 (-Ser-Leu-Gly-Arg-/-Lys-Ile-Gln-Ile) and after Arg76 in complement component C4 (-Gly-Leu-Gln-Arg-/-Ala-Leu-Glu-Ile)
mechanism
Selective cleavage after Arg223 in complement component C2 (-Ser-Leu-Gly-Arg-/-Lys-Ile-Gln-Ile) and after Arg76 in complement component C4 (-Gly-Leu-Gln-Arg-/-Ala-Leu-Glu-Ile)
substrate recognition mechanism, mechanism of complement cascade activation
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
214915-16-9
-
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
complement component C2 + H2O
?
-
the complement C3 convertase C4bC2b is generated by cleavage of complement C4 and complement C2
-
?
complement component C4 + H2O
?
-
the complement C3 convertase C4bC2b is generated by cleavage of complement C4 and complement C2
-
?
Protein + H2O
?
enzyme circulates as a complex with mannose-binding protein, minimal functional unit for complement activation is a ASP homodimer bound to two mannose-binding protein trimeric subunits, complex is formed more readily in the presence of Ca2+
-
?
complement component C2 + H2O
2 fragments of complement component C2
-
involved in activation of complement cascade
-
-
?
complement component C2 + H2O
2 fragments of complement component C2
-
only the activated enzyme binds to C2-component
C2a and C2b fragments, preferred substrate
-
?
complement component C4 + H2O
2 fragments of complement C4
-
involved in activation of complement cascade
-
-
?
complement component C4 + H2O
2 fragments of complement C4
-
no activity of the enzyme complexed with myelin basic protein before complex activation by binding to a suitable carbohydrate ligand
C4a fragment, an N-terminal portion, and C4b fragment, the activated form
-
?
prothrombin + H2O
thrombin + propeptide of thrombin
-
activation of thrombin covalentyl bound to a bacterial cell surface
-
-
?
prothrombin + H2O
thrombin + propeptide of thrombin
-
cleavage scheme, overview
-
-
?
additional information
?
-
-
the enzyme binds to the mannan-binding lectin, the complex activates the lectin pathway of the complement system, MASP-2 is the major protease of the lectin pathway besides MASP-1 and the minor component MASP-3, autoactivation of MASP-2 is the first step in the complement cascade, MASP-3 might be able to downregulate MASP-2 activity, overview
-
-
?
additional information
?
-
-
the enzyme is part of the lectin pathway of the complement system, it is also capable of promoting fibrinogen turnover by cleavage of prothrombin, generating thrombin
-
-
?
additional information
?
-
-
MASP-2 interactions with wild-type and mutant ficolins, overview
-
-
?
additional information
?
-
-
MASP2 acts in a mannan-bound MBL/MASP2 complex
-
-
?
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
Protein + H2O
?
enzyme circulates as a complex with mannose-binding protein, minimal functional unit for complement activation is a ASP homodimer bound to two mannose-binding protein trimeric subunits, complex is formed more readily in the presence of Ca2+
-
?
complement component C2 + H2O
2 fragments of complement component C2
-
involved in activation of complement cascade
-
-
?
complement component C4 + H2O
2 fragments of complement C4
-
involved in activation of complement cascade
-
-
?
prothrombin + H2O
thrombin + propeptide of thrombin
-
activation of thrombin covalentyl bound to a bacterial cell surface
-
-
?
additional information
?
-
-
the enzyme binds to the mannan-binding lectin, the complex activates the lectin pathway of the complement system, MASP-2 is the major protease of the lectin pathway besides MASP-1 and the minor component MASP-3, autoactivation of MASP-2 is the first step in the complement cascade, MASP-3 might be able to downregulate MASP-2 activity, overview
-
-
?
additional information
?
-
-
the enzyme is part of the lectin pathway of the complement system, it is also capable of promoting fibrinogen turnover by cleavage of prothrombin, generating thrombin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
-
Ca2+-dependent dimerization, Ca2+ is bound to the distal end of the CUB1 module of MAp19 and of MASP-2
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
myelin basic protein
-
no activity with substrate C4-component of the enzyme complexed with myelin basic protein before activation of the complex by binding to a suitable carbohydrate ligand
-
additional information
-
MASP-3 might be able to downregulate MASP-2 activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ficolin
-
MASP-2 interactions and activation activity with wild-type and mutant ficolins, overview
-
additional information
-
autoactivation activity is enhanced by complex formation with myelin basic protein, thus myelin basic protein has a regulating function
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
recombinant MASP-2K: kinetics of free enzyme and enzyme complexed with myelin basic protein
-
additional information
additional information
-
kinetics of MASP-2 interactions with wild-type and mutant ficolins, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
MASP-2 is associated with mannan-binding lectin II
-
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). MASP2_RAT
685
0
75667
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
74000
2 * 74000, SDS-PAGE, homodimers are stable in the presence of Ca2+
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
Ca2+-dependent homodimerization, no formation of heterodimers between MASP-2 and MAp19, eventhough they share the same N-terminal domains
additional information
-
enzyme structure and domain organization: CUB1 module, EGF module, CUB2 module, CCP1, CCP2, and serine protease domains, overview
dimer
2 * 74000, SDS-PAGE, homodimers are stable in the presence of Ca2+
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
zymogen is cleaved into the catalytically active protease
proteolytic modification
proteolytic modification
-
autoproteolytic activation of the zymogen, cleavage site contains a Lys residue near the C-terminus, cleavage into 2 fragements, a larger N-termnal and a smaller C-terminal one, the latter contains the protease active site, autoactivation activity is enhanced by complex formation with myelin basic protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structures of Ca2+-bound MASP dimers. Solution structures of the CUB1-EGF-CUB2 dimer indicate that the two CUB2 domains are tilted by 90 degreees compared with the crystal structures. Solution structures of the full-length MASP dimers in their zymogen and activated forms reveal similar structures that are much more bent than anticipated. MASP-2 and its activator MASP-1 are flexible at multiple sites and this flexibility may permit both intra- and inter-complex activation
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R424K
S613A
-
site-directed mutagenesis, the mutant zymogen cannot autoactivate and is secreted in the zymogen form
additional information
R424K
-
site-directed mutagenesis, mutation at the zymogen cleavage site, yielding an active form of MASP2 that is secreted as zymogen but is more stable than wild-type MASP2, since it only autoactivates in complex with MBL upon binding to a suitable surface
R424K
-
site-directed mutagenesis, the mutant shows a reduced autoactivation rate, due to more slowly autoactivation reaction compared to the wild-type enzyme, with reduced zymogen activation during biosynthesis, secretion, and purification
additional information
-
construction of an enzymatically inactive enzyme, also not exhibiting autocatalytic activity, by substitution of the active size catalytic Ser residue with alanine, i.e. MASP-2A, construction of a zymogen with reduced autoproteolytic activity by substitution of the Arg residue at the autocatalytic cleavage site with lysine, i.e. MASP-2K
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
MASP-2K mutant, inhibited in autoproteolytic activation, by affinity chromatography on an myelin basic protein-resin
-
secreted recombinant catalytically active and inactive wild-type and mutant MASP-2 zymogens from CHO cell culture medium
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Chinese hamster ovary cells, recombinant wild type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis
-
expression of catalytically active and inactive wild-type and mutant MASP-2 zymogens in CHO cells, enzyme secretion
-
MASP-2 promoter sequence analysis, phylogenetic analysis, expression regulation involves Stat3 and StatB, Stat3 is more important, overview
-
the MASP-2 catalytic SP-domain is encoded by a single exon, evolutionary aspects, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Feinberg, H.; Uitdehaag, J.C.M.; Davies, J.M.; Wallis, R.; Drickamer, K.; Weis, W.I.
Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2
EMBO J.
22
2348-2359
2003
Rattus norvegicus (Q9JJS8)
Chen, C.B.; Wallis, R.
Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases
J. Biol. Chem.
279
26058-26065
2004
Rattus norvegicus
Sorensen, R.; Thiel, S.; Jensenius, J.C.
Mannan-binding-lectin-associated serine proteases, characteristics and disease associations
Semin. Immunopathol.
27
299-319
2005
Homo sapiens (O00187), Rattus norvegicus (Q9JJS8)
Gal, P.; Barna, L.; Kocsis, A.; Zavodszky, P.
Serine proteases of the classical and lectin pathways: similarities and differences
Immunobiology
212
267-277
2007
Homo sapiens, Rattus norvegicus
Unterberger, C.; Hanson, S.; Klingenhoff, A.; Oesterle, D.; Frankenberger, M.; Endo, Y.; Matsushita, M.; Fujita, T.; Schwaeble, W.; Weiss, E.H.; Ziegler-Heitbrock, L.; Stover, C.
Stat3 is involved in control of gene expression
Biochem. Biophys. Res. Commun.
364
1022-1025
2007
Homo sapiens, Mus musculus (Q91WP0), Mus musculus, Rattus norvegicus
Girija, U.V.; Dodds, A.W.; Roscher, S.; Reid, K.B.; Wallis, R.
Localization and characterization of the mannose-binding lectin (MBL)-associated-serine protease-2 binding site in rat ficolin-A: equivalent binding sites within the collagenous domains of MBLs and ficolins
J. Immunol.
179
455-462
2007
Rattus norvegicus
Krarup, A.; Wallis, R.; Presanis, J.S.; Gal, P.; Sim, R.B.
Simultaneous activation of complement and coagulation by MBL-associated serine protease 2
PLoS ONE
2
e623
2007
Rattus norvegicus
Venkatraman Girija, U.; Furze, C.; Toth, J.; Schwaeble, W.J.; Mitchell, D.A.; Keeble, A.H.; Wallis, R.
Engineering novel complement activity into a pulmonary surfactant protein
J. Biol. Chem.
285
10546-10552
2010
Rattus norvegicus
Phillips, A.E.; Toth, J.; Dodds, A.W.; Girija, U.V.; Furze, C.M.; Pala, E.; Sim, R.B.; Reid, K.B.; Schwaeble, W.J.; Schmid, R.; Keeble, A.H.; Wallis, R.
Analogous interactions in initiating complexes of the classical and lectin pathways of complement
J. Immunol.
182
7708-7717
2009
Rattus norvegicus (Q9JJS8)
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