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 15377
PubChem			22247451 962 22247451 962

1nziA01	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1nziB01	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1nziA02	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1nziB02	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1elvA03	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1elvA01	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1elvA02	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
1nziB01
1nziA02
1nziB02
1elvA03
1elvA01	HIS 460;ASP 514
1elvA02	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.

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