Masp2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001855 complement component C4b binding	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO from human MASP2: binding of complement C4b. Reason: MASP-2 binds its substrate C4 through accessory sites in the CCP-SP region and continues to bind the C4b product after cleavage, which is thought to localise C4b deposition near the activating complex. This is real but ancillary to the core C4/C2-cleaving protease activity, so kept as non-core. Supporting Evidence: PMID:17204478 Following cleavage of C4, C4b still binds to MASP-2 PMID:15060079 Once these sites become exposed, MASP-2 binds to C4 while separate structural changes create a functional catalytic site able to cleave C4.
GO:0001867 complement activation, lectin pathway	IBA GO_REF:0000033	ACCEPT	Summary: IBA (PAINT) lectin-pathway complement activation, seeded on human MASP2 and mouse Masp2. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0001867 complement activation, lectin pathway	ISO GO_REF:0000121	ACCEPT	Summary: ISO from mouse Masp2 (MGI) with acts_upstream_of_or_within; mouse Masp2-deficient phenotype in lectin pathway activity. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. The mouse loss-of-function source is consistent with the direct biochemical role. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0001867 complement activation, lectin pathway	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 lectin-pathway complement activation. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0001867 complement activation, lectin pathway	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 lectin-pathway complement activation. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0001867 complement activation, lectin pathway	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 lectin-pathway complement activation. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0001867 complement activation, lectin pathway	ISS GO_REF:0000024	ACCEPT	Summary: ISS (UniProt) from human MASP2 lectin-pathway complement activation. Reason: MASP-2 is the protease that initiates the lectin pathway: on binding of MBL or ficolins to pathogen carbohydrate, MASP-2 is activated and itself cleaves C4 and C2 to form the C3 convertase C4b2a. Rat MASP-2 has been shown directly to be part of the rat MBL activation complex and to cleave C4 and C2. Core process. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex
GO:0002752 cell surface pattern recognition receptor signaling pathway	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: ISO from human MASP2: cell surface pattern recognition receptor signaling pathway. Reason: The lectin pathway is initiated by soluble pattern-recognition molecules (MBL, ficolins) binding microbial carbohydrate, with MASP-2 acting as an extracellular protease; it is a proteolytic cascade, not intracellular signalling initiated by a cell surface PRR. The term (signalling downstream of a host cell-surface receptor) misdescribes MASP-2 participation; lectin-pathway complement activation (GO:0001867, accepted) captures the biology. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:O00187 SUPPORTS SOURCE BUT NOT TARGET Human MASP2 participates in pattern recognition by soluble MBL/ficolin complexes, but the cell-surface receptor signalling term does not describe that role for either ortholog. Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade.
GO:0004252 serine-type endopeptidase activity	IBA GO_REF:0000033	ACCEPT	Summary: IBA (PAINT) serine-type endopeptidase activity across the C1r/C1s/MASP clade; the target appears among the descendant sources. Reason: Rat MASP-2 is a chymotrypsin-fold (peptidase S1) serine endopeptidase. Recombinant rat MASP-2 autoactivates and cleaves C4 and C2 at single Arg-X bonds; mutating the active-site Ser613 (mature numbering; Ser632 of Q9JJS8) abolishes activity. Core molecular function. Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 MASP-2A is a catalytically inactive form in which the active site serine at position 613 has been replaced by an alanine. file:rat/Masp2/Masp2-uniprot.txt Belongs to the peptidase S1 family.
GO:0004252 serine-type endopeptidase activity	IDA PMID:15060079 Two mechanisms for mannose-binding protein modulation of the...	ACCEPT	Summary: IDA from rat recombinant zymogen and activated MASP-2 (Chen and Wallis 2004). Reason: Rat MASP-2 is a chymotrypsin-fold (peptidase S1) serine endopeptidase. Recombinant rat MASP-2 autoactivates and cleaves C4 and C2 at single Arg-X bonds; mutating the active-site Ser613 (mature numbering; Ser632 of Q9JJS8) abolishes activity. Core molecular function. Abstract-only cache, but the abstract directly reports rat MASP-2 cleavage of C4 and C2. Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:15060079 MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP.MASP-2 complexes bind to a glycan-coated surface
GO:0004252 serine-type endopeptidase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA (InterPro/ARBA) serine-type endopeptidase activity. Reason: Rat MASP-2 is a chymotrypsin-fold (peptidase S1) serine endopeptidase. Recombinant rat MASP-2 autoactivates and cleaves C4 and C2 at single Arg-X bonds; mutating the active-site Ser613 (mature numbering; Ser632 of Q9JJS8) abolishes activity. Core molecular function. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Belongs to the peptidase S1 family. PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade.
GO:0004252 serine-type endopeptidase activity	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 serine-type endopeptidase activity. Reason: Rat MASP-2 is a chymotrypsin-fold (peptidase S1) serine endopeptidase. Recombinant rat MASP-2 autoactivates and cleaves C4 and C2 at single Arg-X bonds; mutating the active-site Ser613 (mature numbering; Ser632 of Q9JJS8) abolishes activity. Core molecular function. Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 MASP-2A is a catalytically inactive form in which the active site serine at position 613 has been replaced by an alanine.
GO:0004252 serine-type endopeptidase activity	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 B chain serine-type endopeptidase activity. Reason: Rat MASP-2 is a chymotrypsin-fold (peptidase S1) serine endopeptidase. Recombinant rat MASP-2 autoactivates and cleaves C4 and C2 at single Arg-X bonds; mutating the active-site Ser613 (mature numbering; Ser632 of Q9JJS8) abolishes activity. Core molecular function. Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 MASP-2A is a catalytically inactive form in which the active site serine at position 613 has been replaced by an alanine.
GO:0005509 calcium ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: IEA (InterPro Ca2+-binding EGF) calcium ion binding. Reason: MASP-2 CUB1, EGF and CUB2 domains carry Ca2+ sites that are required for Ca2+-dependent binding to MBL collagenous stalks. True and structurally grounded, but an ancillary feature of the assembly rather than the core activity. Supporting Evidence: PMID:10913141 both MASPs associate independently with rat MBP in a Ca(2+)-dependent manner PMID:22167201 There are four MBL collagen-binding sites on each MASP-2 (or MASP-1) dimer, and one MBL site within each CUB domains that is near a Ca2+ site (57, 58).
GO:0005576 extracellular region	EXP PMID:10913141 Interaction of mannose-binding protein with associated serin...	ACCEPT	Summary: EXP: recombinant rat MASP-2 fragments secreted (Wallis and Dodd 2000). Reason: Rat MASP-2 is a hepatically synthesised, secreted plasma protein with a cleavable signal peptide; it circulates in complex with MBL. Extracellular region is correct; the more specific extracellular space term is obsolete in current GO, so the row is kept as is. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. PMID:10586086 demonstrate their exclusively hepatic biosynthesis
GO:0005576 extracellular region	IBA GO_REF:0000033	ACCEPT	Summary: IBA extracellular region for the secreted S1 complement proteases. Reason: Rat MASP-2 is a hepatically synthesised, secreted plasma protein with a cleavable signal peptide; it circulates in complex with MBL. Extracellular region is correct; the more specific extracellular space term is obsolete in current GO, so the row is kept as is. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. PMID:10586086 demonstrate their exclusively hepatic biosynthesis
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: IEA (InterPro/SubCell) extracellular region. Reason: Rat MASP-2 is a hepatically synthesised, secreted plasma protein with a cleavable signal peptide; it circulates in complex with MBL. Extracellular region is correct; the more specific extracellular space term is obsolete in current GO, so the row is kept as is. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. PMID:10586086 demonstrate their exclusively hepatic biosynthesis
GO:0005576 extracellular region	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 extracellular region. Reason: Rat MASP-2 is a hepatically synthesised, secreted plasma protein with a cleavable signal peptide; it circulates in complex with MBL. Extracellular region is correct; the more specific extracellular space term is obsolete in current GO, so the row is kept as is. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. PMID:10586086 demonstrate their exclusively hepatic biosynthesis
GO:0005576 extracellular region	ISS GO_REF:0000024	ACCEPT	Summary: ISS (UniProt) extracellular region. Reason: Rat MASP-2 is a hepatically synthesised, secreted plasma protein with a cleavable signal peptide; it circulates in complex with MBL. Extracellular region is correct; the more specific extracellular space term is obsolete in current GO, so the row is kept as is. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. PMID:10586086 demonstrate their exclusively hepatic biosynthesis
GO:0005794 Golgi apparatus	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: ISO from human MASP2: Golgi apparatus. Reason: MASP-2 is a secreted plasma protease made in hepatocytes; it transits the Golgi on the secretory route like any secreted glycoprotein, but no evidence places it as a Golgi resident or functioning there. Per the organelle policy the root organelle claim was examined and does not hold as a location of the mature protein, so the row is an over-annotation from secretory transit (probably antibody staining in the human source). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:O00187 SOURCE WEAK OR INFERRED Golgi signal for a secreted plasma protease reflects biosynthetic transit, not a functional location. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269\|PubMed:10913141}. file:rat/Masp2/Masp2-uniprot.txt Highly expressed in liver. Secreted in plasma. file:rat/Masp2/Masp2-deep-research-manual.md Golgi apparatus (secretory transit only)
GO:0006508 proteolysis	IEA GO_REF:0000002	MODIFY	Summary: IEA (InterPro trypsin domain) proteolysis. Reason: Correct but general. The proteolytic events MASP-2 performs are activation of complement zymogens (C4, C2) and its own autocatalytic activation cleavage; both zymogen activation (GO:0031638, already carried) and protein autoprocessing (GO:0016540, proposed NEW) are is_a descendants of proteolysis (checked with OAK). Proposed replacements: zymogen activation protein autoprocessing Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:15060079 MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP.MASP-2 complexes bind to a glycan-coated surface PMID:20118239 Recombinant wild-type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis.
GO:0006508 proteolysis	ISO GO_REF:0000121	MODIFY	Summary: ISO from human MASP2 proteolysis. Reason: Correct but general. The proteolytic events MASP-2 performs are activation of complement zymogens (C4, C2) and its own autocatalytic activation cleavage; both zymogen activation (GO:0031638, already carried) and protein autoprocessing (GO:0016540, proposed NEW) are is_a descendants of proteolysis (checked with OAK). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS TRANSFER Proteolysis is true of human and rat MASP-2; the specific zymogen-activation and autoprocessing terms are preferable. Proposed replacements: zymogen activation protein autoprocessing Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:15060079 MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP.MASP-2 complexes bind to a glycan-coated surface PMID:20118239 Recombinant wild-type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis.
GO:0006956 complement activation	IEA GO_REF:0000002	MODIFY	Summary: IEA (InterPro C1r/C1s/MASP family) complement activation. Reason: Correct but general: MASP-2 acts specifically in the lectin pathway, and complement activation, lectin pathway (GO:0001867, already carried with IBA/ISO/ISS) is an is_a descendant of complement activation. Proposed replacements: complement activation, lectin pathway Supporting Evidence: PMID:20118239 In the lectin pathway, mannose-binding lectin (MBL)5 and serum ficolins bind to terminal mannose-like epitopes or N-acetyl groups on pathogens to activate MBL-associated serine protease-2 (MASP-2). PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade.
GO:0006956 complement activation	NAS PMID:10586086 The rat and mouse homologues of MASP-2 and MAp19, components...	MODIFY	Summary: NAS from the rat MASP-2/MAp19 cloning paper (Stover et al. 1999). Reason: Correct but general: MASP-2 acts specifically in the lectin pathway, and complement activation, lectin pathway (GO:0001867, already carried with IBA/ISO/ISS) is an is_a descendant of complement activation. The paper itself describes MASP-2 as a constituent of the MBL pathway activation complex. Proposed replacements: complement activation, lectin pathway Supporting Evidence: PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex PMID:10586086 MASP-2 cleaves the fourth complement component C4
GO:0008233 peptidase activity	IDA PMID:15060079 Two mechanisms for mannose-binding protein modulation of the...	MODIFY	Summary: IDA peptidase activity from rat recombinant MASP-2 (Chen and Wallis 2004). Reason: Correct but general: MASP-2 is specifically a serine-type endopeptidase (peptidase S1, catalytic triad His/Asp/Ser), which the gene already carries (GO:0004252, a descendant of peptidase activity). Proposed replacements: serine-type endopeptidase activity Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 MASP-2A is a catalytically inactive form in which the active site serine at position 613 has been replaced by an alanine.
GO:0008233 peptidase activity	ISO GO_REF:0000121	MODIFY	Summary: ISO from human MASP2 peptidase activity. Reason: Correct but general: MASP-2 is specifically a serine-type endopeptidase (peptidase S1, catalytic triad His/Asp/Ser), which the gene already carries (GO:0004252, a descendant of peptidase activity). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS TRANSFER Peptidase activity is true for both orthologs; serine-type endopeptidase activity is the precise term. Proposed replacements: serine-type endopeptidase activity Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 MASP-2A is a catalytically inactive form in which the active site serine at position 613 has been replaced by an alanine.
GO:0009986 cell surface	IEA GO_REF:0000044	MODIFY	Summary: IEA (UniProt SubCell SL-0310 mapping) cell surface. Reason: MASP-2 is not on the host cell surface; UniProt notes it is recruited to the surface of pathogens by MBL, and C4b generated by MASP-2 deposits covalently on the pathogen surface. GO:0009986 cell surface denotes the external part of the cell wall/plasma membrane of the annotated organism, so the appropriate term is symbiont cell surface (GO:0106139), which the gene already carries (lateral correction; not a descendant). Proposed replacements: symbiont cell surface Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Note=Recruited to the surface of pathogens by the mannose-binding proteins, such as MBL2. PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester PMID:20118239 indicating that all MBLs activate only on a carbohydrate target
GO:0009986 cell surface	ISO GO_REF:0000121	MODIFY	Summary: ISO from human MASP2 cell surface. Reason: MASP-2 is not on the host cell surface; UniProt notes it is recruited to the surface of pathogens by MBL, and C4b generated by MASP-2 deposits covalently on the pathogen surface. GO:0009986 cell surface denotes the external part of the cell wall/plasma membrane of the annotated organism, so the appropriate term is symbiont cell surface (GO:0106139), which the gene already carries (lateral correction; not a descendant). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS SOURCE BUT NOT TARGET The human surface location is the pathogen surface; transferred as host cell surface. Proposed replacements: symbiont cell surface Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Note=Recruited to the surface of pathogens by the mannose-binding proteins, such as MBL2. PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester PMID:20118239 indicating that all MBLs activate only on a carbohydrate target
GO:0009986 cell surface	ISS GO_REF:0000024	MODIFY	Summary: ISS (UniProt) from human MASP2 cell surface. Reason: MASP-2 is not on the host cell surface; UniProt notes it is recruited to the surface of pathogens by MBL, and C4b generated by MASP-2 deposits covalently on the pathogen surface. GO:0009986 cell surface denotes the external part of the cell wall/plasma membrane of the annotated organism, so the appropriate term is symbiont cell surface (GO:0106139), which the gene already carries (lateral correction; not a descendant). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS SOURCE BUT NOT TARGET The human surface location is the pathogen surface; transferred as host cell surface. Proposed replacements: symbiont cell surface Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Note=Recruited to the surface of pathogens by the mannose-binding proteins, such as MBL2. PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester PMID:20118239 indicating that all MBLs activate only on a carbohydrate target
GO:0031638 zymogen activation	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2 B chain: zymogen activation. Reason: MASP-2 performs zymogen activation: it cleaves the complement zymogens C4 and C2 to their active fragments, and its own zymogen autoactivates (rat MASP-2 shown directly). Core process at the level of the proteolytic step. Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:15060079 MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP.MASP-2 complexes bind to a glycan-coated surface PMID:20118239 Recombinant wild-type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis.
GO:0042802 identical protein binding	ISO GO_REF:0000121	MODIFY	Summary: ISO from human MASP2: identical protein binding. Reason: MASP-2 forms a Ca2+-independent homodimer through its CUB1-EGF region (shown for rat MASP-2 fragments and the rat CUB1-EGF-CUB2 crystal structure). The more precise protein homodimerization activity (GO:0042803, is_a identical protein binding, checked with OAK) is supported. Non-core assembly property. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS TRANSFER Homodimerisation is shared by human and rat MASP-2; the specific homodimerisation term is preferable. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:10913141 each truncated MASP is a Ca(2+)-independent homodimer in solution PMID:12743029 The CUB1-EGF-CUB2 region mediates homodimerization and binding to MBP.
GO:0048306 calcium-dependent protein binding	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO from human MASP2: calcium-dependent protein binding. Reason: Rat MASP-2 binds the collagen-like stalks of MBL in a Ca2+-dependent manner via its N-terminal CUB1-EGF-CUB2 region; this is how it joins the recognition complex. True, assembly-level, non-core. Supporting Evidence: PMID:10913141 both MASPs associate independently with rat MBP in a Ca(2+)-dependent manner PMID:14724269 MASPs bind on the C-terminal side of the hinge region
GO:0051604 protein maturation	ISO GO_REF:0000121	MODIFY	Summary: ISO from human MASP2: protein maturation. Reason: The maturation events MASP-2 carries out are proteolytic activation of zymogens (C4, C2 and its own zymogen). Zymogen activation (GO:0031638, already carried) and protein autoprocessing (GO:0016540) express this precisely; in the current GO release neither is a descendant of protein maturation (checked with OAK), so this is a lateral refinement to the terms that state the actual step. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O00187 SUPPORTS TRANSFER True for both orthologs in the sense of zymogen activation; the more informative terms are preferred. Proposed replacements: zymogen activation protein autoprocessing Supporting Evidence: PMID:15060079 MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. PMID:20118239 Recombinant wild-type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis.
GO:0106139 symbiont cell surface	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2: is_active_in symbiont cell surface. Reason: MASP-2 acts where MBL/ficolin complexes bind microbial carbohydrate: it is recruited to pathogen surfaces and deposits C4b there; rat MASP-2 activates only when MBL engages a carbohydrate target. is_active_in symbiont cell surface is appropriate. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Note=Recruited to the surface of pathogens by the mannose-binding proteins, such as MBL2. PMID:20118239 indicating that all MBLs activate only on a carbohydrate target PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester
GO:0106139 symbiont cell surface	ISS GO_REF:0000024	ACCEPT	Summary: ISS (UniProt) from human MASP2 B chain: is_active_in symbiont cell surface. Reason: MASP-2 acts where MBL/ficolin complexes bind microbial carbohydrate: it is recruited to pathogen surfaces and deposits C4b there; rat MASP-2 activates only when MBL engages a carbohydrate target. is_active_in symbiont cell surface is appropriate. Supporting Evidence: file:rat/Masp2/Masp2-uniprot.txt Note=Recruited to the surface of pathogens by the mannose-binding proteins, such as MBL2. PMID:20118239 indicating that all MBLs activate only on a carbohydrate target PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester
GO:1903028 positive regulation of opsonization	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO from human MASP2: positive regulation of opsonization. Reason: By cleaving C4 so that C4b (and downstream C3b) is deposited covalently on the microbial surface, MASP-2 promotes opsonization. The effect is real but downstream of the core proteolytic step, so non-core. Supporting Evidence: PMID:17204478 generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester
GO:1905370 serine-type endopeptidase complex	ISO GO_REF:0000121	ACCEPT	Summary: ISO from human MASP2: part_of serine-type endopeptidase complex. Reason: MASP-2 is the catalytic subunit of the circulating MBL (or ficolin)-MASP complexes; rat MASP-2 is part of the rat MBL pathway activation complex. No more specific GO complex term exists for MBL-MASP-2 (GO:1905370 descendants are signal peptidase and mitochondrial IMP complexes). Supporting Evidence: PMID:10586086 We show that both MASP-2 and MAp19 are part of the rat MBL pathway activation complex PMID:10913141 both MASPs associate independently with rat MBP in a Ca(2+)-dependent manner
GO:0016540 protein autoprocessing	IDA PMID:15060079 Two mechanisms for mannose-binding protein modulation of the...	NEW	Summary: Proposed: rat MASP-2 autocatalytically cleaves its own zymogen at the Arg-Ile activation bond. Reason: MASP-2 itself performs the activation cleavage of its own zymogen (autoactivation), stimulated when MBL-MASP-2 complexes bind a glycan surface; wild-type rat MASP-2 autoactivates even during biosynthesis, and an Arg424Lys activation-site mutant slows this. The gene product carries out the step (it is both enzyme and substrate), so the term passes the NEW bar; protein autoprocessing is the GO term for exactly this case. MASP-1-mediated activation in serum is an additional route. Supporting Evidence: PMID:15060079 MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP.MASP-2 complexes bind to a glycan-coated surface PMID:20118239 Recombinant wild-type rat MASP-2 is toxic to producing Chinese hamster ovary cells and autoactivates during biosynthesis. PMID:20118239 MASP-2K is a 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. file:rat/Masp2/Masp2-uniprot.txt The uncleaved zymogen is inactive towards synthetic substrates, but has sufficient activity to effect autocatalytic cleavage.

Gene Description

Existing Annotations Review

Core Functions

Lectin-pathway initiating serine protease: when MBL/ficolin-MASP-2 complexes bind microbial carbohydrate, MASP-2 autoactivates and cleaves complement C4 and C2 to assemble the C3 convertase C4b2a on the pathogen surface.

Autocatalytic activation: the MASP-2 zymogen cleaves its own activation bond, a step accelerated by MBL binding to a glycan surface.

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