EzCatDB: M00316
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DB codeM00316
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.3.4.21.42

CATH domainRelated DB codes (homologues)
2.10.25.10 : LamininM00139,M00133,M00212,M00152,M00155,M00315
2.10.70.10 : Complement Module; domain 1M00139,M00155,M00315
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,M00315,M00317,M00348,M00349,T00074,T00410,T00411
2.60.120.290 : Jelly RollsM00139,M00227,M00315,M00317,M00348

Enzyme Name
UniProtKBKEGG

P09871
Protein nameComplement C1s subcomponentComplement subcomponent C_overbar_1s_
C1 esterase
Activated complement C1s
Complement C_overbar_1r_
SynonymsEC 3.4.21.42
C1 esterase
Complement component 1 subcomponent s
ContainsComplement C1s subcomponent heavy chain
Complement C1s subcomponent light chain
RefSeqNP_001725.1 (Protein)
NM_001734.3 (DNA/RNA sequence)
NP_958850.1 (Protein)
NM_201442.2 (DNA/RNA sequence)
MEROPSS01.193 (Serine)
PfamPF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP09871
Entry nameC1S_HUMAN
ActivityCleavage 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.
SubunitC1 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.
Subcellular location
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







                  
1nziA01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nziB01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nziA02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1nziB02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1elvA03UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1elvA01UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1elvA02UnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [3] & Swiss-prot;P09871
pdbCatalytic residuesMain-chain involved in catalysis
          
1nziA01 
 
1nziB01 
 
1nziA02 
 
1nziB02 
 
1elvA03 
 
1elvA01HIS 460;ASP 514
 
1elvA02SER 617
GLY 615;SER 617

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

references
[1]
PubMed ID8172567
JournalBehring Inst Mitt
Year1993
Volume(93)
Pages189-95
AuthorsArlaud GJ, Thielens NM, Illy C
TitleAssembly of the C1 complex.
[2]
PubMed ID9422791
JournalJ Biol Chem
Year1998
Volume273
Pages1232-9
AuthorsRossi V, Bally I, Thielens NM, Esser AF, Arlaud GJ
TitleBaculovirus-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.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 358-688.
PubMed ID10775260
JournalEMBO J
Year2000
Volume19
Pages1755-65
AuthorsGaboriaud C, Rossi V, Bally I, Arlaud GJ, Fontecilla-Camps JC
TitleCrystal structure of the catalytic domain of human complement c1s: a serine protease with a handle.
Related PDB1elv
Related UniProtKBP09871
[4]
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.
[5]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[6]
PubMed ID12413689
JournalMol Immunol
Year2002
Volume39
Pages383-94
AuthorsArlaud GJ, Gaboriaud C, Thielens NM, Budayova-Spano M, Rossi V, Fontecilla-Camps JC
TitleStructural biology of the C1 complex of complement unveils the mechanisms of its activation and proteolytic activity.
[7]
PubMed ID14674770
JournalBiochemistry
Year2003
Volume42
Pages14939-45
AuthorsO'Brien G, Quinsey NS, Whisstock JC, Pike RN
TitleImportance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING SITES, GLYCOSYLATION AT ASN-406.
PubMed ID12788922
JournalJ Biol Chem
Year2003
Volume278
Pages32157-64
AuthorsGregory LA, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
TitleX-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement.
Related PDB1nzi
Related UniProtKBP09871
[9]
PubMed ID15207504
JournalTrends Immunol
Year2004
Volume25
Pages368-73
AuthorsGaboriaud C, Thielens NM, Gregory LA, Rossi V, Fontecilla-Camps JC, Arlaud GJ
TitleStructure and activation of the C1 complex of complement: unraveling the puzzle.
[10]
PubMed ID16169853
JournalJ Biol Chem
Year2005
Volume280
Pages39510-4
AuthorsKerr FK, O'Brien G, Quinsey NS, Whisstock JC, Boyd S, de la Banda MG, Kaiserman D, Matthews AY, Bird PI, Pike RN
TitleElucidation of the substrate specificity of the C1s protease of the classical complement pathway.
[11]
PubMed ID19361285
JournalBiol Chem
Year2009
Volume390
Pages503-7
AuthorsBoyd SE, Kerr FK, Albrecht DW, de la Banda MG, Ng N, Pike RN
TitleCooperative effects in the substrate specificity of the complement protease C1s.
[12]
PubMed ID20592021
JournalJ Biol Chem
Year2010
Volume285
Pages32251-63
AuthorsBrier S, Pflieger D, Le Mignon M, Bally I, Gaboriaud C, Arlaud GJ, Daniel R
TitleMapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex.

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.

createdupdated
2011-03-082012-08-08


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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)
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