EzCatDB: M00315
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DB codeM00315
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.60.120.290 : Jelly Rolls
Domain 22.10.25.10 : Laminin
Domain 32.60.120.290 : Jelly Rolls
Domain 42.10.70.10 : Complement Module; domain 1
Domain 52.10.70.10 : Complement Module; domain 1
Domain 62.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 72.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.104

CATH domainRelated DB codes (homologues)
2.10.25.10 : LamininM00139,M00133,M00212,M00152,M00155,M00316
2.10.70.10 : Complement Module; domain 1M00139,M00155,M00316
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00316,M00317,M00348,M00349,T00074,T00410,T00411
2.60.120.290 : Jelly RollsM00139,M00227,M00316,M00317,M00348

Enzyme Name
UniProtKBKEGG

Q9JJS8O00187
Protein nameMannan-binding lectin serine protease 2Mannan-binding lectin serine protease 2Mannan-binding lectin-associated serine protease-2
MASP-2
MASP2
MBP-associated serine protease-2
Mannose-binding lectin-associated serine protease-2
p100
Mannan-binding lectin-associated serine peptidase 2
SynonymsEC 3.4.21.104
MBL-associated serine protease 2
Mannose-binding protein-associated serine protease 2
MASP-2
EC 3.4.21.104
MBL-associated serine protease 2
Mannose-binding protein-associated serine protease 2
MASP-2
ContainsMannan-binding lectin serine protease 2 A chain
Mannan-binding lectin serine protease 2 B chain
Mannan-binding lectin serine protease 2 A chain
Mannan-binding lectin serine protease 2 B chain
RefSeqNP_742040.1 (Protein)
NM_172043.1 (DNA/RNA sequence)
NP_006601.2 (Protein)
NM_006610.3 (DNA/RNA sequence)
NP_631947.1 (Protein)
NM_139208.2 (DNA/RNA sequence)
MEROPSS01.229 (Serine)
S01.229 (Serine)
PfamPF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical view]
PF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberQ9JJS8O00187
Entry nameMASP2_RATMASP2_HUMAN
ActivitySelective cleavage after Arg-223 in complement component C2 (-Ser-Leu-Gly-Arg-|-Lys-Ile-Gln-Ile) and after Arg-76 in complement component C4 (-Gly-Leu-Gln-Arg-|-Ala-Leu-Glu-Ile).Selective cleavage after Arg-223 in complement component C2 (-Ser-Leu-Gly-Arg-|-Lys-Ile-Gln-Ile) and after Arg-76 in complement component C4 (-Gly-Leu-Gln-Arg-|-Ala-Leu-Glu-Ile).
SubunitHomodimer. disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1 By similarity.Homodimer. disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1. Dimerization and MBL2 binding requires calcium ions. of C3. Interacts with SERPING1.
Subcellular locationSecreted.Secreted.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idL00082L00083C00001L00084L00085L00086L00080I00087I00085I00086
CompoundComplement component C2Complement component C4H2OComplement component C2aComplement component C2bComplement component C4aComplement component C4bPeptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/proteinpeptide/proteinpeptide/protein


ChEBI

15377







PubChem

962
22247451







                  
1nt0A01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nt0G01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1szbA01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1szbB01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nt0A02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nt0G02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1szbA02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1szbB02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nt0A03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nt0G03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zjkA01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xA01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xB01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zjkA02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3tvjAUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xA02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xB02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zjkA03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3tvjB01UnboundAnalogue:LYS 30-LEU 31(chain I) UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xA03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1q3xB03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zjkA04UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3tvjB02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [11], [14] & Swiss-prot;O00187
pdbCatalytic residuesMain-chain involved in catalysis
          
1nt0A01 
 
1nt0G01 
 
1szbA01 
 
1szbB01 
 
1nt0A02 
 
1nt0G02 
 
1szbA02 
 
1szbB02 
 
1nt0A03 
 
1nt0G03 
 
1zjkA01 
 
1q3xA01 
 
1q3xB01 
 
1zjkA02 
 
3tvjA 
 
1q3xA02SER 633
GLY 631;SER 633
1q3xB02SER 633
GLY 631;SER 633
1zjkA03SER 633
GLY 631;SER 633
3tvjB01SER 633
GLY 631;SER 633
1q3xA03HIS 483;ASP 532
 
1q3xB03HIS 483;ASP 532
 
1zjkA04HIS 483;ASP 532
 
3tvjB02HIS 483;ASP 532
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Figure 5, p.4505-4508

references
[1]
CommentsFUNCTION, INTERACTION WITH SERPING1.
PubMed ID10946292
JournalJ Immunol
Year2000
Volume165
Pages2637-42
AuthorsMatsushita M, Thiel S, Jensenius JC, Terai I, Fujita T
TitleProteolytic activities of two types of mannose-binding lectin-associated serine protease.
[2]
PubMed ID10925294
JournalJ Immunol
Year2000
Volume165
Pages2093-100
AuthorsVorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC
TitleDistinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.
[3]
PubMed ID12369900
JournalCurr Protein Pept Sci
Year2001
Volume2
Pages43-59
AuthorsGal P, Ambrus G
TitleStructure and function of complement activating enzyme complexes: C1 and MBL-MASPs.
[4]
PubMed ID11527969
JournalJ Biol Chem
Year2001
Volume276
Pages40880-7
AuthorsRossi V, Cseh S, Bally I, Thielens NM, Jensenius JC, Arlaud GJ
TitleSubstrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2.
[5]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[6]
PubMed ID12396007
JournalImmunobiology
Year2002
Volume205
Pages455-66
AuthorsSchwaeble W, Dahl MR, Thiel S, Stover C, Jensenius JC
TitleThe mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 20-299, HYDROXYLATION AT ASN-158, DISULFIDE BONDS, GLYCOSYLATION AT ASN-103.
PubMed ID12743029
JournalEMBO J
Year2003
Volume22
Pages2348-59
AuthorsFeinberg H, Uitdehaag JC, Davies JM, Wallis R, Drickamer K, Weis WI
TitleCrystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2.
Related PDB1nt0
Related UniProtKBQ9JJS8
[8]
PubMed ID12538697
JournalJ Immunol
Year2003
Volume170
Pages1374-82
AuthorsAmbrus G, Gal P, Kojima M, Szilagyi K, Balczer J, Antal J, Graf L, Laich A, Moffatt BE, Schwaeble W, Sim RB, Zavodszky P
TitleNatural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments.
[9]
PubMed ID15060079
JournalJ Biol Chem
Year2004
Volume279
Pages26058-65
AuthorsChen CB, Wallis R
TitleTwo mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 16-181 (ISOFORM 2), CHARACTERIZATION OF VARIANT GLY-120, CALCIUM-BINDING SITES, DIMERIZATION, MUTAGENESIS OF TYR-74; TYR-121 AND GLU-124, INTERACTION WITH MBL2 AND FCN2, DISULFIDE BONDS.
PubMed ID15117939
JournalJ Biol Chem
Year2004
Volume279
Pages29391-7
AuthorsGregory LA, Thielens NM, Matsushita M, Sorensen R, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
TitleThe X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.
Related PDB1szb
Related UniProtKBO00187
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 363-686, DISULFIDE BONDS.
PubMed ID15364579
JournalJ Mol Biol
Year2004
Volume342
Pages1533-46
AuthorsHarmat V, Gal P, Kardos J, Szilagyi K, Ambrus G, Vegh B, Naray-Szabo G, Zavodszky P
TitleThe structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions.
Related PDB1q3x
Related UniProtKBO00187
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF 287-686, AUTOCATALYTIC CLEAVAGE AT ARG-444, MUTAGENESIS OF ARG-444.
PubMed ID16040602
JournalJ Biol Chem
Year2005
Volume280
Pages33435-44
AuthorsGal P, Harmat V, Kocsis A, Bian T, Barna L, Ambrus G, Vegh B, Balczer J, Sim RB, Naray-Szabo G, Zavodszky P
TitleA true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations.
Related PDB1zjk
Related UniProtKBO00187
[13]
PubMed ID17709141
JournalMol Immunol
Year2008
Volume45
Pages670-7
AuthorsKerr FK, Thomas AR, Wijeyewickrema LC, Whisstock JC, Boyd SE, Kaiserman D, Matthews AY, Bird PI, Thielens NM, Rossi V, Pike RN
TitleElucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor.
[14]
PubMed ID19477526
JournalMol Immunol
Year2009
Volume46
Pages2745-52
AuthorsGal P, Dobo J, Zavodszky P, Sim RB
TitleEarly complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions.
[15]
PubMed ID22511776
JournalJ Biol Chem
Year2012
Volume287
Pages20290-300
AuthorsHeja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G
TitleMonospecific inhibitors show that both mannan-binding lectin-associated serine protease-1 (MASP-1) and -2 Are essential for lectin pathway activation and reveal structural plasticity of MASP-2.
Related PDB3tvj

comments
This enzyme belongs to peptidase family-S1.
This enzyme (MASP-2) can activate C2 and C4 in the lectin pathway of the complement system (see [3], [9]). The products of this enzyme, C4b and C2a, bind to form C3 convertase, which activates another complement component, C3.
This enzyme is involved in "lectin pathway" of complement system, whereas a homologous enzyme, Complement subcomponent C1s (M00316 in EzCatDB), is involved in "classical pathway" of complement system. The lectin pathway is an antibody-independent activation route of the complement system (see [15]). It provides immediate defense against pathogens and altered self-cells (see [15]).
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

createdupdated
2011-02-242012-08-10


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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