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Information on EC 3.4.21.41 - complement subcomponent C1r and Organism(s) Homo sapiens
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3.4.21.41 complement subcomponent C1rSpecify your search results
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
proteases c1r, c1r-lp, xolloid, c1r protease, complement subcomponent c1r, complement protease c1r, c1r serine protease, complement c1r subcomponent-like protein, serine protease c1r, multiprotein complex c1, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
activated complement C1r
-
-
-
-
C1r
C1rbar-esterase
-
-
-
-
complement C1r, activated
-
-
-
-
multiprotein complex C1
the multiprotein complex C1 is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2
CAS REGISTRY NUMBER
COMMENTARY
80295-69-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
benzyloxycarbonyl-Lys-thiobenzyl ester + H2O
benzyloxycarbonyl-Lys + phenylmethanethiol
-
-
-
?
MASP-3 K448Q zymogen + H2O
active MASP-3 protein + ?
poor activity with the wild-type MASP-3
-
-
?
N-acetyl-Gly-Lys methyl ester + H2O
N-acetyl-Gly-Lys + methanol
-
-
-
-
?
N-carbobenzoxy-Lys-p-nitrophenyl ester + H2O
N-carbobenzoxy-Lys + 4-nitrophenyl
-
-
-
-
?
N-carbobenzoxy-Tyr-p-nitrophenyl ester + H2O
N-carbobenzoxy-Tyr + 4-nitrophenol
-
-
-
-
?
prohaptoglobin + H2O
haptoglobin + ?
the enzyme cleaves prohaptoglobin after arginine R102 in variants Hp1F and Hp1S or after R161 in variant Hp2FS
-
-
?
complement C1q zymogen + H2O
active complement C1q + ?
no or reduced activity with substrate mutants K59A, K61A, K58A, and K58A/K59A/K61A
-
-
?
complement component C1s
?
-
binding of C1 to activator is mediated by C1q and triggers activation of proenzyme C1r into an active protease C1rbar, which in turn activates C1s, thereby initiating the classical pathway of complement
-
-
?
complement component C1s
?
-
activates the proenzyme form of C1s by limited proteolysis
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system, interaction anaylsis of the C1 complex and regulatory proteins, overview
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
C1r cleaves proenzyme C1s at an Arg-Ile bond in the serine domain
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
C1r cleaves proenzyme C1s at an Arg-Ile bond in the serine domain, enzyme-product binding structure, overview
-
-
?
complement component C1s + H2O
complement component C1sbar
-
cleavage of a single Arg-Ile or Lys-Ile bond in C1s
-
-
?
complement component C1s + H2O
complement component C1sbar
-
cleavage of a single Arg-Ile bond in the sequence Lys-Gln-Arg-Ile-Ile-Gly
-
-
?
complement component C1s + H2O
complement component C1sbar
-
C1rbar does not hydrolyze any amino acid ester tested nor any protein substrate except subcomponent C1s
-
-
?
complement component C1s + H2O
complement component C1sbar
-
C1R and its activated fragments all cleave C1s, in the order of increasing efficiency: C21r, CCP1/2-SP, CCP2-SP. CCP1 is not involved in C1s recognition
-
?
zymogen C1s + H2O
active C1s protease + ?
the enzyme is active with the substrate fragment consisting of complement control protein domains, CCP1 and CCP2, plus serine protease domain of wild-type and mutant Q462N, Q462G, I464A, and Q462N/I464A forms of C1s, mutant Q462N/I464A substrate gives very low activity
-
-
?
additional information
?
-
-
the ability of autoactivation of C1r and C1s cleavage activity is an inherent property of the SP domain
-
?
additional information
?
-
the enzyme recognizes the a short collagen-like peptide containing the sequence Hyp-Gly-Lys-Leu-Gly-Pro
-
-
?
additional information
?
-
the residues found in the activation loop of the zymogens capable of being activated by enzyme C1r play a major role in recognition of the active site of enzyme C1r
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
prohaptoglobin + H2O
haptoglobin + ?
the enzyme cleaves prohaptoglobin after arginine R102 in variants Hp1F and Hp1S or after R161 in variant Hp2FS
-
-
?
complement component C1s
?
-
binding of C1 to activator is mediated by C1q and triggers activation of proenzyme C1r into an active protease C1rbar, which in turn activates C1s, thereby initiating the classical pathway of complement
-
-
?
complement component C1s
?
-
activates the proenzyme form of C1s by limited proteolysis
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system
-
-
?
complement component C1s + H2O
activated complement component C1s + ?
-
the enzyme is part of the Ca2+-dependent tetramer C1s-C1r-C1r-C1s, termed as C1 complex, which is associated with the recognition molecule C1q, autoactivation of C1r, which then activates proenzyme C1s through cleavage at an Arg-Ile bond in the serine domain, C1r is active in the classical pathway of the complement system, interaction anaylsis of the C1 complex and regulatory proteins, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
-
the NH2-terminal alpha fragment of the enzyme contains one high affinity Ca2+ binding site
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
C1-inhibitor
-
regulates the classical and the lectin complement pathway inhibiting complement components C1r and C1s, and MASP-2, factor XIa, Factor XIIa, and plasma kallikrein, mechanism, overview
-
C1INH
-
sole inhibitor of the activated proteases C1r and C1s. Hereditary angioedema results from functional deficiency of the C1 inhibitor (C1INH) protein, which plays a key role in the classical pathway of complement activation
-
C1 inhibitor
-
during complex formation, C1 inhibitor dissociates C1r and C1s from the activated C1 macromolecule, a process that is determined primarily by the interaction with C1r
-
C1bar-inhibitor
-
Ca2+ decreases the rate at which C1rbar complexes with C1bar-inhibitor. C1rbar-(C1bar-inhibitor) interaction is accelerated by heparin. Flufenamic acid inhibits the action of the inhibitor
-
additional information
-
above 0.0005 mM C1rbar the enzyme aggregates with loss of activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the recognition molecule C1q to the C1 complex triggers its autoactivation via C1r, the C-reactive protein, CRP, activates the C1 complex by binding to C1q
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000022
zymogen C1s
pH 7.4, 37°C, substrate is a fragment consisting of complement control protein domains, CCP1 and CCP2, plus serine
-
additional information
additional information
-
activated C1r and its wild-type CCP1/2-SP and CCP2-SP fragments all cleave acetyl-Gly-Lys-methyl ester with KM-values ranging from 1.3 mM to 2.1 mM
-
additional information
additional information
-
KM-values of the C1r fragments with benzyloxycarbonyl-Lys-thiobenzyl ester or benzyloxycarbonyl-Gly-Arg-thiobenzyl ester as substrate
-
additional information
additional information
-
kinetic interaction anaylsis of the C1 complex and regulatory proteins, e.g. the C-reactive protein, overview
-
additional information
additional information
kinetics of activation of C1s and MASP-3 mutants, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0645
zymogen C1s
pH 7.4, 37°C, substrate is a fragment consisting of complement control protein domains, CCP1 and CCP2, plus serine
-
additional information
additional information
-
activated C1r and its wild-type CCP1/2-SP and CCP2-SP fragments all cleave acetyl-Gly-Lys-methyl ester with turnover numbers ranging from 8.2 s to 9.2 s
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2900
zymogen C1s
pH 7.4, 37°C, substrate is a fragment consisting of complement control protein domains, CCP1 and CCP2, plus serine
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
binding residues are conserved in the CUB1 domains of C1r, MASP-1/-3, and MASP-2, indicating that the interaction mechanism is conserved in initiating complexes of the lectin and classical pathways
metabolism
physiological function
additional information
metabolism
C1r and C1s pro-enzymes form a heterotetrameric structure that associates with the recognition molecule, C1q, in the C1 complex
metabolism
complement is an important part of the immune system. It is initiated through three different pathways known as the classical, lectin, and alternative pathway. The multimolecular C1 complex of the classical pathway consists of a subcomponent, C1q, which binds to a tetramer comprising two C1r and two C1s proteases, EC 3.4.21.41 and EC 3.4.21.42, respectively
metabolism
hexameric complement C1q is a versatile recognition protein that senses a wide variety of immune and nonimmune ligands, including pathogens and altered self components, and triggers the classical complement pathway through activation of its associated proteases C1r and C1s, EC 3.4.21.42. Residues LysB61 and LysC58 each play a key role in the interaction with C1s-C1r-C1r-C1s, with LysA59 being involved to a lesser degree
physiological function
C1r is a zymogen, activation of C1 occurs when the C1q subcomponent binds to a pathogen via its globular heads resulting in autolytic activation of C1r followed, in turn, by C1r-mediated activation of C1s
physiological function
the large multicomponent assembly C1 complex, binds to immune complexes, protein modulators (e.g., C-reactive protein), and polyanionic structures on pathogens to initiate complement activation. Binding to pathogens induces a conformational change that drives activation of the zymogen proteases in stepwise fashion: C1r first autoactivates, then activates C1s. C1s subsequently cleaves substrates C4 and C4b-bound C2, to form the C3 convertase (C4b2a), the downstream component of the reaction cascade
physiological function
multiprotein complex C1 triggers the destruction of invading pathogens via lysis or by stimulation of innate and adaptive immune processes
additional information
subsite profiling of human C1r using a phage display library with a fixed P1 arginine, specificity determinants, overview. Gln and Ile residues at P2 and P1', respectively, are important for cleavage of phage displayed substrates, the enzyme displays considerable specificity at every position apart from P4, P3', and P4'
additional information
the C1s/C1r/C1r/C1s tetramer forms a complex with C1q by interacting with the stems. C1r is a homologous multidomain protease containing an N-terminal CUB module, an EGF-like module, a second CUB module, two complement control modules CCP, and a serine protease domain SP. The three domains that constitute the catalytic fragment of C1r (CCP1-CCP2-SP) readily form head-to-tail dimers. The CUB1-EGF-CUB2 fragments of C1r also dimerize. Interaction analysis and structure-function relationship, formation of the C1 complex, molecular dynamics simulations and thermodynamics, detailed overview
additional information
the large multicomponent assembly C1 complex is composed of a recognition subcomponent, C1q (460 kDa), and two serine protease subcomponents, C1r (90 kDa) and C1s (80 kDa) in a 1:2:2 ratio, with an overall molecular mass of about790 kDa. C1r is a modular protease with two N-terminal complement C1r/C1s, Uegf and bone morphogenetic protein-1(CUB) domains, separated by an epidermal growth factor (EGF)-ike domain, followed by two complement control modules (CCP) and a C-terminal serine protease (SP) domain
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). C1R_HUMAN
705
0
80119
Swiss-Prot
Secretory Pathway (Reliability: 2)
A0A3B3ISR2_HUMAN
705
0
80174
TrEMBL
Secretory Pathway (Reliability: 2)
B4DPQ0_HUMAN
719
0
81890
TrEMBL
Secretory Pathway (Reliability: 2)
Q53HU9_HUMAN
705
0
80300
TrEMBL
Secretory Pathway (Reliability: 2)
F5H2D0_HUMAN
671
0
76614
TrEMBL
Secretory Pathway (Reliability: 2)
A8K5J8_HUMAN
705
0
80199
TrEMBL
Secretory Pathway (Reliability: 2)
D3DUT5_HUMAN
376
0
42957
TrEMBL
Secretory Pathway (Reliability: 2)
B4E1B0_HUMAN
599
0
68538
TrEMBL
other Location (Reliability: 2)
Q53HT9_HUMAN
705
0
80241
TrEMBL
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
83000
-
2 * 83000, SDS-PAGE of reduced protein, gel filtration in 6 M guanidinium hydrochloride
85000
-
2 * 85000, the C1rbar subunits consist of one polypeptide chain of 56000 Da, A-chain, that is disulfide-linked to a 27000 Da B-chain, SDS-PAGE
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
-
2 * 83000, SDS-PAGE of reduced protein, gel filtration in 6 M guanidinium hydrochloride
dimer
-
2 * 85000, the C1rbar subunits consist of one polypeptide chain of 56000 Da, A-chain, that is disulfide-linked to a 27000 Da B-chain, SDS-PAGE
dimer
-
CCP1 is essential to the assembly of the dimer, but formation of a stable dimer is not a prerequisite for self-activation
dimer
-
deletion of CCP1 domain from CCP1-CCP2-SP fragment results in the loss of the dimeric structure. Dimerization of C1r is not a prerequisite for autoactivation
additional information
-
the C1 complex comprises two loosely interacting subunits, C1q and the Ca2+-dependent C1s-C1r-C1r-C1s tetramer. Binding of C1 to activator is mediated by C1q and triggers activation of proenzyme C1r into an active protease C1rbar, which in turn activates C1s, thereby initiating the classical pathway of complement
additional information
-
on activation the single polypeptide chain of C1r is cleaved probably at a single position, the C1rbar subunits consist of 1 polypeptide chain of 56000 Da, A-chain, that is disulfide-linked to a 27000 Da B-chain
additional information
-
C1rbar and the proenzyme C1r are noncovalent dimers, the subunit of C1r has a MW of 53000-85000 Da, SDS-PAGE
additional information
C1r and C1s pro-enzymes form a heterotetrameric structure that associates with the recognition molecule, C1q, in the C1 complex
additional information
each C1r monomer consists of six domains, CUB1-EGF-CUB2-CCP1-CCP2-SP, i.e. an N-terminal CUB module, an EGF-like module, a second CUB module, two complement control modules CCP, and a serine protease domain SP. The three domains that constitute the catalytic fragment of C1r (CCP1-CCP2-SP) readily form head-to-tail dimers. The CUB1-EGF-CUB2 fragments of C1r also dimerize
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
side-chain modification
proteolytic modification
-
binding of C1 to activator is mediated by C1q and triggers activation of proenzyme C1r into an active protease C1rbar
proteolytic modification
-
activation of C1r involves cleavage of a single peptide bond which converts the proenzyme into active enzyme. Activation of the serine-proteinase domain of C1r is controlled by a Ca2+-dependent intramolecular mechanism involving the Ca2+-binding alpha-region. This control is released in C1 by a signal originating in C1q and transmitted through the C1q/C1r interface
proteolytic modification
-
autolytic proteolysis involves cleavage of the Arg279-Gly280 bond in the sequence Asp-Ser-Arg-Gly-Trp-Lys
proteolytic modification
-
activation of the proenzyme C1r can be mimicked under certain conditions by digestion of C1r with trypsin or plasmin
proteolytic modification
-
the proenzyme C1r is not autoactivatable but undergoes proteolysis by exogenous C1rbar
proteolytic modification
autoactivation of C1r as part of the C1 complex, modeling, overview
side-chain modification
-
the A-chain contains 7.4% carbohydrate and the B-chain contains 12.4% carbohydrate
side-chain modification
-
C1rbar contains about 40 carbohydrate residues per molecule
side-chain modification
-
postranslational modification of C1r by beta-hydroxylation of specific Asp and Asn residues, 10% of the recombinant C1r is hydroxylated
side-chain modification
-
in the case of the recombinant proteins the incompletely processed N-linked carbohydrate chains lack at least the terminal sialic acid residues
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complex between the CUB1-EGF-CUB2 domains of C1r and C1s, sitting drop vapor diffusion method, in imidazole buffer at pH 8.0 with PEG 8000 as the precipitant
hanging drop vapour diffusion method, crystal structure of two fragments from the human C1r catalytic domain, each encompassing the second complement control protein CCP2 module and the SP domain. The wild-type species has an active structure, whereas the S637A mutant is a zymogen
hanging drop vapour diffusion, crystal structure of a mutated proenzyme form of the catalytic domain of human C1r, and the serine protease domain solved and refined to 2.9 A resolution
purified recombinant isolated active catalytic region forming a dimer in a head-to-tail fashion, complex of enzyme and product, hanging drop vapour diffusion method, 15°C, mixing of 0.008 ml protein solution, containing 0.2 mg/ml protein, 20 mM Tris-HCl, pH 7.4, and 130 mM NaC, with 0.008 ml reservoir solution containing 14% w/v PEG 6000, 0.2 M NaCl, 10% v/v glycerol, and 0.1 M Tris-HCl, pH 7.4, cryoprotection of crystals in 20% glycerol, X-ray diffraction structure determination and analysis at 2.6 A resolution, molecular replacement
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I306-C309del
the deletion mutations are associated with periodontal Ehlers-Danlos syndrome
R401-Y405del
the deletion mutations are associated with periodontal Ehlers-Danlos syndrome
R446Q
-
stabilized in the single-chain proenzyme form by mutation at the cleavage site, no esterolytic activity with acetyl-Gly-Lys-methyl ester
R463X
S637A
-
stabilized in the single-chain proenzyme form by mutation at the active site serine residue, no esterolytic activity with acetyl-Gly-Lys-methyl ester
additional information
-
by the point mutation of C1r - Arg-Phe - of the natural cleavage site Arg-Ile - the zymogen is stabilized, while the biological activity is not affected
R463X
-
construction of a stable zymogen by mutating the Arg463Ile bond shows that one active C1r in the C1 complex is sufficient for the full activity of the entire complex
R463X
-
the mutants of the proenzyme Arg463Lys,Ile464Phe have increased stability, they retain their ability to autoactivate and have wild-type like hemolytic activity
R463X
-
the mutations Arg463Gln, Arg463Lys or Arg463Phe all stabilize the zymogen state
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
high temperature transition occurs at 53°C, the low-temperature transition varies between 26°C at low ionic strength and 40°C in the presence of 0.5 M NaCl
additional information
-
high temperature transition occurs at 53°C, the low-temperature transition varies between 26°C at low ionic strength and 40°C in the presence of 0.5 M NaCl
additional information
-
melting transition of SP fragment is 47.5°C, melting point of the CCP2-SP fragment is 55.4°C, the CCP1-CCP2-SP fragment shows an unfolding transition at 57.5°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
after reduction and alkylation C1rbar undergoes proteolytic cleavage which lead to the successive removal of two fragments of 35000 Da and of 7000-10000 Da, leaving a divalent molecule of reduced size. The product C1rbar II retains the original antigenic properties of C1rbar and a functional active site, but loses the capacity to bind C1s
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from inclusion bodies, ion exchange chromatography (Q-Sepharose), gel filtration
-
nickel-Sepharose affinity column chromatography and Superdex 200 gel filtration
recombinant active catalytic region of C1r from Escherichia coli strain BL21(DE3) by ion exchange chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
baculovirus-mediated expression is used to produce fragments containing the SP domain and either 2 CCP modules (CCP1/2-SP) or only the second CCP module (CCP2-SP). In each case the wild-type species and two mutants stabilized in the proenzyme form by mutations at the cleavage site (R446Q) or at the active site serine residue (S637A) are produced
-
CUB2-complement control protein 1 module expressed in Escherichia coli BL21(DE3) pLysS
-
development and evaluation of a method for expression of recombinant full-length human C-terminally tagged C1q involving stable transfection of HEK 293-F mammalian cells
expression of complement control protein module 2 (I356-V433), complement control protein module 1 - complement control protein module 2 (I289-V433), CUB2 - complement control protein module 1 (Q173-D358) and CUB2 - complement control protein module 1 - complement control protein module 2 (Q173-V433)
-
expression of modules: Q173-D358 (CUB2-complement control protein 1) and I356-V433 (complement control protein 2)
-
expression of the isolated active catalytic region, containing the C-terminal serine protease domain, and two preceding complement control protein modules, of C1r in Escherichia coli strain BL21(DE3)
production of the CCP1-CCP2-SP, the CCP2-SP and the SP fragments in Escherichia coli
-
recombinant expression of full-length C1r protease and the CUB1-EGF-CUB2 fragment with low yield
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of the C1 complex using purified C1q, C1r and C1s in the presence of C1-INH, interaction with C-reactive protein CRP, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
anti-inflammatory functions are exerted via inhibition of complement system proteases (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Busby, T.F.; Ingham, K.C.
Calcium-sensitive thermal transitions and domain structure of human complement subcomponent C1r
Biochemistry
26
5564-5571
1987
Homo sapiens
Journet, A.; Tosi, M.
Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r
Biochem. J.
240
783-787
1986
Homo sapiens
Thielens, N.M.; Illy, C.; Bally, I.M.; Arlaud, G.J.
Activation of human complement serine-proteinase C1r is down-regulated by a Ca(2+)-dependent intramolecular control that is released in the C1 complex through a signal transmitted by C1q
Biochem. J.
301
509-516
1994
Homo sapiens
Loos, M.; Clas, F.; Heinz, H.P.
C1rbar-esterase
Methods Enzym. Anal. , 3rd Ed. (Bergmeyer, H. U. , ed. )
5
514-527
1984
Homo sapiens
-
Illy, C.; Thielens, N.M.; Arlaud, G.J.
Chemical characterization and location of ionic interactions involved in the assembly of the C1 complex of human complement
J. Protein Chem.
12
771-781
1993
Homo sapiens
Gal, P.; Zavodzky, P.
Structure and function of the serine-protease subcomponents of C1: protein engineering studies
Immunobiology
199
317-326
1998
Homo sapiens
Andrews, J.M.; Baillie, R.D.
The enzymatic nature of human c1r: a subcomponent of the first component of complement
J. Immunol.
123
1403-1408
1979
Homo sapiens
Sim, R.B.; Porter, R.R.; Reid, K.B.M.; Gigli, I.
The structure and enzymic activities of the C1r and C1s subcomponents of C1, the first component of human serum complement
Biochem. J.
163
219-227
1977
Homo sapiens
Sim, R.; Arlaud, G.J.; Colomb, M.G.
Kinetics of reaction of human C1bar-inhibitor with the human complement system proteases C1rbar and C1sbar
Biochim. Biophys. Acta
612
433-449
1980
Homo sapiens
Sim, R.B.
The human complement system serine proteases C1bar and C1sbar and their proenzymes
Methods Enzymol.
80
26-42
1981
Homo sapiens
Nilsson, T.; Wiman, B.
Kinetics of the reaction between human C1-esterase inhibitor and C1r or C1s
Eur. J. Biochem.
129
663-667
1983
Homo sapiens
Reboul, A.; Bensa, J.C.; Colomb, M.G.
Characteristics of complement subcomponents C1r and C1s synthesized by Hep G2 cells
Biochem. J.
233
559-564
1986
Homo sapiens
Arlaud, G.J.; Villiers, C.L.; Chesne, S.; Colomb, M.G.
Purified proenzyme C1r. Some characteristics of its activation and subsequent proteolytic cleavage
Biochim. Biophys. Acta
616
116-129
1980
Homo sapiens
Thielens, N.M.; Aude, C.A.; Lacroix, M.B.; Gagnon, J.; Arlaud, G.J.
Ca2+ binding properties and Ca2+-dependent interactions of the isolated NH2-terminal alpha fragments of human complement proteases C1rbar and C1sbar
J. Biol. Chem.
265
14469-14475
1990
Homo sapiens
Katz, Y.; Guterman, M.; Lahat, E.
Regulation of synthesis of complement proteins in HEp2 cells
Clin. Immunol. Immunopathol.
67
117-123
1993
Homo sapiens
Zavodszky, P.; Gal, P.; Cseh, S.; Schumaker, V.N.
Protein engineering studies on C1r and C1s
Behring Inst. Mitt.
93
103-114
1993
Homo sapiens
Gulati, P.; Lemercier, C.; Guc, D.; Lappin, D.; Whaley, K.
Regulation of the synthesis of C1 subcomponents and C1-inhibitor
Behring Inst. Mitt.
93
196-203
1993
Homo sapiens
Arlaud, G.J.; Thielens, N.M.
Human complement serine proteases C1r and C1s and their proenzymes
Methods Enzymol.
223
61-82
1993
Homo sapiens
Kam, C.M.; Oglesby, T.J.; Pangburn, M.K.; Volanakis, J.E.; Powers, J.C.
Substituted isocoumarins as inhibitors of complement serine proteases
J. Immunol.
149
163-168
1992
Homo sapiens
Dobo, J.; Gal, P.; Szilagyi, K.; Cseh, S.; Lrincz, Z.; Schumaker, V.N.; Zavodszky, P.
One active C1r subunit is sufficient for the activity of the complement C1 complex: stabilization of C1r in the zymogen form by point mutations
J. Immunol.
162
1108-1112
1999
Homo sapiens
Budayova-Spano, M.; Lacroix, M.; Thielens, N.M.; Arlaud, G.J.; Fontecilla-Camps, J.C.; Gaboriaud, C.
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
EMBO J.
21
231-239
2002
Homo sapiens (P00736), Homo sapiens
Lacroix, M.; Ebel, C.; Kardos, J.; Dobo, J.; Gal, P.; Zavodszky, P.; Arlaud, G.J.; Thielens, N.M.
Assembly and enzymatic properties of the catalytic domain of human complement protease C1r
J. Biol. Chem.
276
36233-36240
2001
Homo sapiens
Kardos, J.; Gal, P.; Szilagyi, L.; Thielens, N.M.; Szilagyi, K.; Lorincz, Z.; Kulcsar, P.; Graf, L.; Arlaud, G.J.; Zavodszky, P.
The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r
J. Immunol.
167
5202-5208
2001
Homo sapiens
Budayova-Spano, M.; Grabarse, W.; Thielens, N.M.; Hillen, H.; Lacroix, M.; Schmidt, M.; Fontecilla-Camps, J.C.; Arlaud, G.J.; Gaboriaud, C.
Monomeric structures of the zymogen and active catalytic domain of complement protease C1r: further insights into the C1 activation mechanism
Structure
10
1509-1519
2002
Homo sapiens (P00736), Homo sapiens
Duncan, R.C.; Wijeyewickrema, L.C.; Pike, R.N.
The initiating proteases of the complement system: controlling the cleavage
Biochimie
90
387-395
2008
Homo sapiens
Biro, A.; Rovo, Z.; Papp, D.; Cervenak, L.; Varga, L.; Fuest, G.; Thielens, N.M.; Arlaud, G.J.; Prohaszka, Z.
Studies on the interactions between C-reactive protein and complement proteins
Immunology
121
40-50
2007
Homo sapiens
Kardos, J.; Harmat, V.; Pallo, A.; Barabas, O.; Szilagyi, K.; Graf, L.; Naray-Szabo, G.; Goto, Y.; Zavodszky, P.; Gal, P.
Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r
Mol. Immunol.
45
1752-1760
2008
Homo sapiens (P00736), Homo sapiens
Goesswein, T.; Kocot, A.; Emmert, G.; Kreuz, W.; Martinez-Saguer, I.; Aygoeren-Puersuen, E.; Rusicke, E.; Bork, K.; Oldenburg, J.; Mueller, C.R.
Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema
Cytogenet. Genome Res.
121
181-188
2008
Homo sapiens
Davis, A.E.; Mejia, P.; Lu, F.
Biological activities of C1 inhibitor
Mol. Immunol.
45
4057-4063
2008
Homo sapiens
Lang, A.; Szilagyi, K.; Major, B.; Gal, P.; Zavodszky, P.; Perczel, A.
Intermodule cooperativity in the structure and dynamics of consecutive complement control modules in human C1r: structural biology
FEBS J.
277
3986-3998
2010
Homo sapiens
Lang, A.; Major, B.; Szilagyi, K.; Gaspari, Z.; Gal, P.; Zavodszky, P.; Perczel, A.
Interaction between separated consecutive complement control modules of human C1r: implications for dimerization of the full-length protease
FEBS Lett.
584
4565-4569
2010
Homo sapiens
Major, B.; Kardos, J.; Kekesi, K.A.; Lorincz, Z.; Zavodszky, P.; Gal, P.
Calcium-dependent conformational flexibility of a CUB domain controls activation of the complement serine protease C1r
J. Biol. Chem.
285
11863-11869
2010
Homo sapiens
Brier, S.; Pflieger, D.; Le Mignon, M.; Bally, I.; Gaboriaud, C.; Arlaud, G.J.; Daniel, R.
Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex
J. Biol. Chem.
285
32251-32263
2010
Homo sapiens
Valck, C.; Ramirez, G.; Lopez, N.; Ribeiro, C.H.; Maldonado, I.; Sanchez, G.; Ferreira, V.P.; Schwaeble, W.; Ferreira, A.
Molecular mechanisms involved in the inactivation of the first component of human complement by Trypanosoma cruzi calreticulin
Mol. Immunol.
47
1516-1521
2010
Homo sapiens
Kaplan, A.P.; Ghebrehiwet, B.
The plasma bradykinin-forming pathways and its interrelationships with complement
Mol. Immunol.
47
2161-2169
2010
Homo sapiens
Wijeyewickrema, L.C.; Yongqing, T.; Tran, T.P.; Thompson, P.E.; Viljoen, J.E.; Coetzer, T.H.; Duncan, R.C.; Kass, I.; Buckle, A.M.; Pike, R.N.
Molecular determinants of the substrate specificity of the complement-initiating protease, C1r
J. Biol. Chem.
288
15571-15580
2013
Homo sapiens (P00736)
Venkatraman Girija, U.; Gingras, A.R.; Marshall, J.E.; Panchal, R.; Sheikh, M.A.; Gal, P.; Schwaeble, W.J.; Mitchell, D.A.; Moody, P.C.; Wallis, R.
Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation
Proc. Natl. Acad. Sci. USA
110
13916-13920
2013
Homo sapiens (P00736)
Bally, I.; Ancelet, S.; Moriscot, C.; Gonnet, F.; Mantovani, A.; Daniel, R.; Schoehn, G.; Arlaud, G.J.; Thielens, N.M.
Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites
Proc. Natl. Acad. Sci. USA
110
8650-8655
2013
Homo sapiens (P00736), Homo sapiens
Beveridge, A.J.; Wallis, R.; Samani, N.J.
A molecular dynamics study of C1r and C1s dimers: implications for the structure of the C1 complex
Proteins
80
1987-1997
2012
Homo sapiens (P00736)
Kapferer-Seebacher, I.; Pepin, M.; Werner, R.; Aitman, T.J.; Nordgren, A.; Stoiber, H.; Thielens, N.; Gaboriaud, C.; Amberger, A.; Schossig, A.; Gruber, R.; Giunta, C.; Bamshad, M.; Bjoerck, E.; Chen, C.; Chitayat, D.; Dorschner, M.; Schmitt-Egenolf, M.; Hale, C.J.; Hanna, D.; Hennies, H.C.; Heiss-Kisielewsky, I.
Periodontal Ehlers-Danlos syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement
Am. J. Hum. Genet.
99
1005-1014
2016
Homo sapiens (P00736)
Schaer, C.A.; Owczarek, C.; Deuel, J.W.; Schauer, S.; Baek, J.H.; Yalamanoglu, A.; Hardy, M.P.; Scotney, P.D.; Schmidt, P.M.; Pelzing, M.; Soupourmas, P.; Buehler, P.W.; Schaer, D.J.
Phenotype-specific recombinant haptoglobin polymers co-expressed with C1r-like protein as optimized hemoglobin-binding therapeutics
BMC Biotechnol.
18
15
2018
Homo sapiens (Q9NZP8), Homo sapiens
Almitairi, J.O.M.; Venkatraman Girija, U.; Furze, C.M.; Simpson-Gray, X.; Badakshi, F.; Marshall, J.E.; Schwaeble, W.J.; Mitchell, D.A.; Moody, P.C.E.; Wallis, R.
Structure of the C1r-C1s interaction of the C1 complex of complement activation
Proc. Natl. Acad. Sci. USA
115
768-773
2018
Homo sapiens (P00736)
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