DB code: M00315

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.60.120.290 : Jelly Rolls
2.10.25.10 : Laminin
2.60.120.290 : Jelly Rolls
2.10.70.10 : Complement Module; domain 1
2.10.70.10 : Complement Module; domain 1
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.104
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.10.25.10 : Laminin M00139 M00133 M00212 M00152 M00155 M00316
2.10.70.10 : Complement Module; domain 1 M00139 M00155 M00316
2.40.10.10 : Thrombin, subunit H M00139 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 Rolls M00139 M00227 M00316 M00317 M00348

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
Q9JJS8 Mannan-binding lectin serine protease 2
EC 3.4.21.104
MBL-associated serine protease 2
Mannose-binding protein-associated serine protease 2
MASP-2
Mannan-binding lectin serine protease 2 A chain
Mannan-binding lectin serine protease 2 B chain
NP_742040.1 (Protein)
NM_172043.1 (DNA/RNA sequence)
S01.229 (Serine)
PF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical View]
O00187 Mannan-binding lectin serine protease 2
EC 3.4.21.104
MBL-associated serine protease 2
Mannose-binding protein-associated serine protease 2
MASP-2
Mannan-binding lectin serine protease 2 A chain
Mannan-binding lectin serine protease 2 B chain
NP_006601.2 (Protein)
NM_006610.3 (DNA/RNA sequence)
NP_631947.1 (Protein)
NM_139208.2 (DNA/RNA sequence)
S01.229 (Serine)
PF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Mannan-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O00187 MASP2_HUMAN 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). Homodimer. disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1. Dimerization and MBL2 binding requires calcium ions. of C3. Interacts with SERPING1. Secreted.
Q9JJS8 MASP2_RAT 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). Homodimer. disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1 By similarity. Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00082 L00083 C00001 L00084 L00085 L00086 L00080 I00087 I00085 I00086
E.C.
Compound Complement component C2 Complement component C4 H2O Complement component C2a Complement component C2b Complement component C4a Complement component C4b Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1nt0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nt0G01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1szbA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1szbB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nt0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nt0G02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1szbA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1szbB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nt0A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nt0G03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zjkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zjkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3tvjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zjkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3tvjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:LYS_30-LEU_31(chain I) Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1q3xB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zjkA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3tvjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [11], [14] & Swiss-prot;O00187

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1nt0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nt0G01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1szbA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1szbB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nt0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nt0G02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1szbA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1szbB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nt0A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nt0G03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1zjkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1q3xA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1q3xB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1zjkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3tvjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1q3xA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 633 GLY 631;SER 633
1q3xB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 633 GLY 631;SER 633
1zjkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 633 GLY 631;SER 633
3tvjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 633 GLY 631;SER 633
1q3xA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 483;ASP 532
1q3xB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 483;ASP 532
1zjkA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 483;ASP 532
3tvjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 483;ASP 532

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
Figure 5, p.4505-4508

References
[1]
Resource
Comments FUNCTION, INTERACTION WITH SERPING1.
Medline ID
PubMed ID 10946292
Journal J Immunol
Year 2000
Volume 165
Pages 2637-42
Authors Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T
Title Proteolytic activities of two types of mannose-binding lectin-associated serine protease.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10925294
Journal J Immunol
Year 2000
Volume 165
Pages 2093-100
Authors Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC
Title Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12369900
Journal Curr Protein Pept Sci
Year 2001
Volume 2
Pages 43-59
Authors Gal P, Ambrus G
Title Structure and function of complement activating enzyme complexes: C1 and MBL-MASPs.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11527969
Journal J Biol Chem
Year 2001
Volume 276
Pages 40880-7
Authors Rossi V, Cseh S, Bally I, Thielens NM, Jensenius JC, Arlaud GJ
Title Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12475199
Journal Chem Rev
Year 2002
Volume 102
Pages 4501-24
Authors Hedstrom L
Title Serine protease mechanism and specificity.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12396007
Journal Immunobiology
Year 2002
Volume 205
Pages 455-66
Authors Schwaeble W, Dahl MR, Thiel S, Stover C, Jensenius JC
Title The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 20-299, HYDROXYLATION AT ASN-158, DISULFIDE BONDS, GLYCOSYLATION AT ASN-103.
Medline ID
PubMed ID 12743029
Journal EMBO J
Year 2003
Volume 22
Pages 2348-59
Authors Feinberg H, Uitdehaag JC, Davies JM, Wallis R, Drickamer K, Weis WI
Title Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2.
Related PDB 1nt0
Related UniProtKB Q9JJS8
[8]
Resource
Comments
Medline ID
PubMed ID 12538697
Journal J Immunol
Year 2003
Volume 170
Pages 1374-82
Authors Ambrus G, Gal P, Kojima M, Szilagyi K, Balczer J, Antal J, Graf L, Laich A, Moffatt BE, Schwaeble W, Sim RB, Zavodszky P
Title Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15060079
Journal J Biol Chem
Year 2004
Volume 279
Pages 26058-65
Authors Chen CB, Wallis R
Title Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-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.
Medline ID
PubMed ID 15117939
Journal J Biol Chem
Year 2004
Volume 279
Pages 29391-7
Authors Gregory LA, Thielens NM, Matsushita M, Sorensen R, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
Title The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.
Related PDB 1szb
Related UniProtKB O00187
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 363-686, DISULFIDE BONDS.
Medline ID
PubMed ID 15364579
Journal J Mol Biol
Year 2004
Volume 342
Pages 1533-46
Authors Harmat V, Gal P, Kardos J, Szilagyi K, Ambrus G, Vegh B, Naray-Szabo G, Zavodszky P
Title The 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 PDB 1q3x
Related UniProtKB O00187
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF 287-686, AUTOCATALYTIC CLEAVAGE AT ARG-444, MUTAGENESIS OF ARG-444.
Medline ID
PubMed ID 16040602
Journal J Biol Chem
Year 2005
Volume 280
Pages 33435-44
Authors Gal P, Harmat V, Kocsis A, Bian T, Barna L, Ambrus G, Vegh B, Balczer J, Sim RB, Naray-Szabo G, Zavodszky P
Title A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations.
Related PDB 1zjk
Related UniProtKB O00187
[13]
Resource
Comments
Medline ID
PubMed ID 17709141
Journal Mol Immunol
Year 2008
Volume 45
Pages 670-7
Authors Kerr FK, Thomas AR, Wijeyewickrema LC, Whisstock JC, Boyd SE, Kaiserman D, Matthews AY, Bird PI, Thielens NM, Rossi V, Pike RN
Title Elucidation 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.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 19477526
Journal Mol Immunol
Year 2009
Volume 46
Pages 2745-52
Authors Gal P, Dobo J, Zavodszky P, Sim RB
Title Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 22511776
Journal J Biol Chem
Year 2012
Volume 287
Pages 20290-300
Authors Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G
Title Monospecific 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 PDB 3tvj
Related UniProtKB

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.

Created Updated
2011-02-24 2012-08-10