DB code: M00139

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. 3.4.21.41
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.10.25.10 : Laminin M00133 M00212 M00152 M00155 M00315 M00316
2.10.70.10 : Complement Module; domain 1 M00155 M00315 M00316
2.40.10.10 : Thrombin, subunit H 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 M00316 M00317 M00348 M00349 T00074 T00410 T00411
2.60.120.290 : Jelly Rolls M00227 M00315 M00316 M00317 M00348

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P00736 Complement C1r subcomponent
EC 3.4.21.41
Complement component 1, r subcomponent
Complement C1r subcomponent heavy chain
Complement C1r subcomponent light chain
NP_001724.3 (Protein)
NM_001733.4 (DNA/RNA sequence)
S01.192 (Serine)
PF00431 (CUB)
PF07645 (EGF_CA)
PF00084 (Sushi)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
complement subcomponent C_overbar_1r_
activated complement C1r
C_overbar_1r_ esterase
activated complement C1r

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00736 C1R_HUMAN Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42). C1 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.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00087 C00001 L00088 I00087 I00085 I00086
E.C.
Compound Complement subcomponent C1s H2O Complement subcomponent C1s- Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 962
22247451
1apqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md7A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1gpzB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1md8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot & literature [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1apqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gpzA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gpzB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gpzA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gpzB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1md7A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1md8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gpzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 485;ASP 540
1gpzB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 485;ASP 540
1md7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 485;ASP 540
1md8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 485;ASP 540
1gpzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 637 GLY 635;SER 637
1gpzB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 637 GLY 635;SER 637
1md7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 635; mutant S637A
1md8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 637 GLY 635;SER 637

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.111

References
[1]
Resource
Comments
Medline ID
PubMed ID 6281332
Journal J Immunol
Year 1982
Volume 128
Pages 2500-4
Authors Ziccardi RJ
Title Spontaneous activation of the first component of human complement (C1) by an intramolecular autocatalytic mechanism.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2842400
Journal J Immunol
Year 1988
Volume 141
Pages 1610-4
Authors Hosoi S, Borsos T
Title Activation of human C1r: Western blot analysis reveals slow and dose-dependent activation.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2539098
Journal Biochem J
Year 1989
Volume 257
Pages 885-91
Authors Lacroix MB, Aude CA, Arlaud GJ, Colomb MG
Title Isolation and functional characterization of the proenzyme form of the catalytic domains of human C1r.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8216203
Journal Biochem J
Year 1993
Volume 295
Pages 109-14
Authors Perkins SJ, Smith KF
Title Identity of the putative serine-proteinase fold in proteins of the complement system with nine relevant crystal structures.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9174342
Journal Biochemistry
Year 1997
Volume 36
Pages 6270-82
Authors Lacroix M, Rossi V, Gaboriaud C, Chevallier S, Jaquinod M, Thielens NM, Gagnon J, Arlaud GJ
Title Structure and assembly of the catalytic region of human complement protease C1r: a three-dimensional model based on chemical cross-linking and homology modeling.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9151255
Journal J Pept Res
Year 1997
Volume 49
Pages 221-31
Authors Hernandez JF, Bersch B, Petillot Y, Gagnon J, Arlaud GJ
Title Chemical synthesis and characterization of the epidermal growth factor-like module of human complement protease C1r.
Related PDB
Related UniProtKB
[7]
Resource
Comments STRUCTURE BY NMR OF 140-192.
Medline ID 98138432
PubMed ID 9477945
Journal Biochemistry
Year 1998
Volume 37
Pages 1204-14
Authors Bersch B, Hernandez JF, Marion D, Arlaud GJ
Title Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
Related PDB 1apq
Related UniProtKB P00736
[8]
Resource
Comments
Medline ID
PubMed ID 9777414
Journal Immunobiology
Year 1998
Volume 199
Pages 303-16
Authors Arlaud GJ, Rossi V, Thielens NM, Gaboriaud C, Bersch B, Hernandez JF
Title Structural and functional studies on C1r and C1s: new insights into the mechanisms involved in C1 activity and assembly.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9777415
Journal Immunobiology
Year 1998
Volume 199
Pages 317-26
Authors Gal P, Zavodszky P
Title Structure and function of the serine-protease subcomponents of C1: protein engineering studies.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11414355
Journal Immunol Rev
Year 2001
Volume 180
Pages 136-45
Authors Arlaud GJ, Gaboriaud C, Thielens NM, Rossi V, Bersch B, Hernandez JF, Fontecilla-Camps JC
Title Structural biology of C1: dissection of a complex molecular machinery.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11445589
Journal J Biol Chem
Year 2001
Volume 276
Pages 36233-40
Authors Lacroix M, Ebel C, Kardos J, Dobo J, Gal P, Zavodszky P, Arlaud GJ, Thielens NM
Title Assembly and enzymatic properties of the catalytic domain of human complement protease C1r.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11823416
Journal EMBO J
Year 2002
Volume 21
Pages 231-9
Authors Budayova-Spano M, Lacroix M, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C
Title The 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 PDB 1gpz
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12429092
Journal Structure (Camb)
Year 2002
Volume 10
Pages 1509-19
Authors Budayova-Spano M, Grabarse W, Thielens NM, Hillen H, Lacroix M, Schmidt M, Fontecilla-Camps JC, Arlaud GJ, Gaboriaud C
Title Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.
Related PDB 1md7 1md8
Related UniProtKB

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.

Created Updated
2004-03-19 2012-08-08