EzCatDB: M00139
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DB codeM00139
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.3.4.21.41

CATH domainRelated DB codes (homologues)
2.10.25.10 : LamininM00133,M00212,M00152,M00155,M00315,M00316
2.10.70.10 : Complement Module; domain 1M00155,M00315,M00316
2.40.10.10 : Thrombin, subunit HD00214,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,M00316,M00317,M00348,M00349,T00074,T00410,T00411
2.60.120.290 : Jelly RollsM00227,M00315,M00316,M00317,M00348

Enzyme Name
UniProtKBKEGG

P00736
Protein nameComplement C1r subcomponentcomplement subcomponent C_overbar_1r_
activated complement C1r
C_overbar_1r_ esterase
activated complement C1r
SynonymsEC 3.4.21.41
Complement component 1, r subcomponent
ContainsComplement C1r subcomponent heavy chain
Complement C1r subcomponent light chain
RefSeqNP_001724.3 (Protein)
NM_001733.4 (DNA/RNA sequence)
MEROPSS01.192 (Serine)
PfamPF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP00736
Entry nameC1R_HUMAN
ActivitySelective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42).
SubunitC1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idL00087C00001L00088I00087I00085I00086
CompoundComplement subcomponent C1sH2OComplement subcomponent C1s-Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinH2Opeptide/protein


ChEBI
15377




PubChem
962
22247451




              
1apqAUnbound Unbound   
1gpzA04Unbound Unbound   
1gpzB04Unbound Unbound   
1gpzA03Unbound Unbound   
1gpzB03Unbound Unbound   
1md7A03Unbound Unbound   
1md8A03Unbound Unbound   
1gpzA01Unbound Unbound   
1gpzB01Unbound Unbound   
1md7A01Unbound Unbound   
1md8A01Unbound Unbound   
1gpzA02Unbound Unbound   
1gpzB02Unbound Unbound   
1md7A02Unbound Unbound   
1md8A02Unbound Unbound   

Active-site residues
resource
Swiss-prot & literature [4]
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1apqA 
 
 
1gpzA04 
 
 
1gpzB04 
 
 
1gpzA03 
 
 
1gpzB03 
 
 
1md7A03 
 
 
1md8A03 
 
 
1gpzA01HIS 485;ASP 540
 
 
1gpzB01HIS 485;ASP 540
 
 
1md7A01HIS 485;ASP 540
 
 
1md8A01HIS 485;ASP 540
 
 
1gpzA02SER 637
GLY 635;SER 637
 
1gpzB02SER 637
GLY 635;SER 637
 
1md7A02       
GLY 635;       
mutant S637A
1md8A02SER 637
GLY 635;SER 637
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.111

references
[1]
PubMed ID6281332
JournalJ Immunol
Year1982
Volume128
Pages2500-4
AuthorsZiccardi RJ
TitleSpontaneous activation of the first component of human complement (C1) by an intramolecular autocatalytic mechanism.
[2]
PubMed ID2842400
JournalJ Immunol
Year1988
Volume141
Pages1610-4
AuthorsHosoi S, Borsos T
TitleActivation of human C1r: Western blot analysis reveals slow and dose-dependent activation.
[3]
PubMed ID2539098
JournalBiochem J
Year1989
Volume257
Pages885-91
AuthorsLacroix MB, Aude CA, Arlaud GJ, Colomb MG
TitleIsolation and functional characterization of the proenzyme form of the catalytic domains of human C1r.
[4]
PubMed ID8216203
JournalBiochem J
Year1993
Volume295
Pages109-14
AuthorsPerkins SJ, Smith KF
TitleIdentity of the putative serine-proteinase fold in proteins of the complement system with nine relevant crystal structures.
[5]
PubMed ID9174342
JournalBiochemistry
Year1997
Volume36
Pages6270-82
AuthorsLacroix M, Rossi V, Gaboriaud C, Chevallier S, Jaquinod M, Thielens NM, Gagnon J, Arlaud GJ
TitleStructure and assembly of the catalytic region of human complement protease C1r: a three-dimensional model based on chemical cross-linking and homology modeling.
[6]
PubMed ID9151255
JournalJ Pept Res
Year1997
Volume49
Pages221-31
AuthorsHernandez JF, Bersch B, Petillot Y, Gagnon J, Arlaud GJ
TitleChemical synthesis and characterization of the epidermal growth factor-like module of human complement protease C1r.
[7]
CommentsSTRUCTURE BY NMR OF 140-192.
Medline ID98138432
PubMed ID9477945
JournalBiochemistry
Year1998
Volume37
Pages1204-14
AuthorsBersch B, Hernandez JF, Marion D, Arlaud GJ
TitleSolution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
Related PDB1apq
Related UniProtKBP00736
[8]
PubMed ID9777414
JournalImmunobiology
Year1998
Volume199
Pages303-16
AuthorsArlaud GJ, Rossi V, Thielens NM, Gaboriaud C, Bersch B, Hernandez JF
TitleStructural and functional studies on C1r and C1s: new insights into the mechanisms involved in C1 activity and assembly.
[9]
PubMed ID9777415
JournalImmunobiology
Year1998
Volume199
Pages317-26
AuthorsGal P, Zavodszky P
TitleStructure and function of the serine-protease subcomponents of C1: protein engineering studies.
[10]
PubMed ID11414355
JournalImmunol Rev
Year2001
Volume180
Pages136-45
AuthorsArlaud GJ, Gaboriaud C, Thielens NM, Rossi V, Bersch B, Hernandez JF, Fontecilla-Camps JC
TitleStructural biology of C1: dissection of a complex molecular machinery.
[11]
PubMed ID11445589
JournalJ Biol Chem
Year2001
Volume276
Pages36233-40
AuthorsLacroix M, Ebel C, Kardos J, Dobo J, Gal P, Zavodszky P, Arlaud GJ, Thielens NM
TitleAssembly and enzymatic properties of the catalytic domain of human complement protease C1r.
[12]
PubMed ID11823416
JournalEMBO J
Year2002
Volume21
Pages231-9
AuthorsBudayova-Spano M, Lacroix M, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
TitleThe crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex.
Related PDB1gpz
[13]
PubMed ID12429092
JournalStructure (Camb)
Year2002
Volume10
Pages1509-19
AuthorsBudayova-Spano M, Grabarse W, Thielens NM, Hillen H, Lacroix M, Schmidt M, Fontecilla-Camps JC, Arlaud GJ, Gaboriaud C
TitleMonomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.
Related PDB1md7,1md8

comments
This enzyme belongs to the peptidase family-S1.
According to the literature [4], this enzyme has got a similar catalytic triad (Ser/His/Asp) to that of trypsin, suggesting a similar mechanism.

createdupdated
2004-03-192012-08-08


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