DB code: M00316

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. 3.4.21.42
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.10.25.10 : Laminin M00139 M00133 M00212 M00152 M00155 M00315
2.10.70.10 : Complement Module; domain 1 M00139 M00155 M00315
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 M00315 M00317 M00348 M00349 T00074 T00410 T00411
2.60.120.290 : Jelly Rolls M00139 M00227 M00315 M00317 M00348

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P09871 Complement C1s subcomponent
EC 3.4.21.42
C1 esterase
Complement component 1 subcomponent s
Complement C1s subcomponent heavy chain
Complement C1s subcomponent light chain
NP_001725.1 (Protein)
NM_001734.3 (DNA/RNA sequence)
NP_958850.1 (Protein)
NM_201442.2 (DNA/RNA sequence)
S01.193 (Serine)
PF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Complement subcomponent C_overbar_1s_
C1 esterase
Activated complement C1s
Complement C_overbar_1r_

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P09871 C1S_HUMAN Cleavage of Arg-|-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase. C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.

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
1nziA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nziB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nziA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1nziB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1elvA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1elvA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1elvA02 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 [3] & Swiss-prot;P09871

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1nziA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nziB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nziA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1nziB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1elvA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1elvA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 460;ASP 514
1elvA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 617 GLY 615;SER 617

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

References
[1]
Resource
Comments
Medline ID
PubMed ID 8172567
Journal Behring Inst Mitt
Year 1993
Volume (93)
Pages 189-95
Authors Arlaud GJ, Thielens NM, Illy C
Title Assembly of the C1 complex.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9422791
Journal J Biol Chem
Year 1998
Volume 273
Pages 1232-9
Authors Rossi V, Bally I, Thielens NM, Esser AF, Arlaud GJ
Title Baculovirus-mediated expression of truncated modular fragments from the catalytic region of human complement serine protease C1s. Evidence for the involvement of both complement control protein modules in the recognition of the C4 protein substrate.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 358-688.
Medline ID
PubMed ID 10775260
Journal EMBO J
Year 2000
Volume 19
Pages 1755-65
Authors Gaboriaud C, Rossi V, Bally I, Arlaud GJ, Fontecilla-Camps JC
Title Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle.
Related PDB 1elv
Related UniProtKB P09871
[4]
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
[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 12413689
Journal Mol Immunol
Year 2002
Volume 39
Pages 383-94
Authors Arlaud GJ, Gaboriaud C, Thielens NM, Budayova-Spano M, Rossi V, Fontecilla-Camps JC
Title Structural biology of the C1 complex of complement unveils the mechanisms of its activation and proteolytic activity.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 14674770
Journal Biochemistry
Year 2003
Volume 42
Pages 14939-45
Authors O'Brien G, Quinsey NS, Whisstock JC, Pike RN
Title Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING SITES, GLYCOSYLATION AT ASN-406.
Medline ID
PubMed ID 12788922
Journal J Biol Chem
Year 2003
Volume 278
Pages 32157-64
Authors Gregory LA, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
Title X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement.
Related PDB 1nzi
Related UniProtKB P09871
[9]
Resource
Comments
Medline ID
PubMed ID 15207504
Journal Trends Immunol
Year 2004
Volume 25
Pages 368-73
Authors Gaboriaud C, Thielens NM, Gregory LA, Rossi V, Fontecilla-Camps JC, Arlaud GJ
Title Structure and activation of the C1 complex of complement: unraveling the puzzle.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 16169853
Journal J Biol Chem
Year 2005
Volume 280
Pages 39510-4
Authors Kerr FK, O'Brien G, Quinsey NS, Whisstock JC, Boyd S, de la Banda MG, Kaiserman D, Matthews AY, Bird PI, Pike RN
Title Elucidation of the substrate specificity of the C1s protease of the classical complement pathway.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 19361285
Journal Biol Chem
Year 2009
Volume 390
Pages 503-7
Authors Boyd SE, Kerr FK, Albrecht DW, de la Banda MG, Ng N, Pike RN
Title Cooperative effects in the substrate specificity of the complement protease C1s.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 20592021
Journal J Biol Chem
Year 2010
Volume 285
Pages 32251-63
Authors Brier S, Pflieger D, Le Mignon M, Bally I, Gaboriaud C, Arlaud GJ, Daniel R
Title Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to peptidase family-S1.
A complement component, C1, is a trimolecular complex of the recognition protein C1q and the catalytic subunit C1s-C1r-C1r-C1s that consists of homologus serine proteases, C1r (see M00139 in EzCatDB) and C1s (this enzyme) (see [1]). C1r (M00139) activates C1s (this enzyme), so that it can activate C2 and C4 in the pathway of the complement system (see [6], [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 "classical pathway" of complement system, whereas a homologous enzyme, mannose-binding lectin-associated serine protease 2 (M00315 in EzCatDB), is involved in "lectin pathway" of complement system.
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

Created Updated
2011-03-08 2012-08-08