Affinage

C1R

Complement C1r subcomponent · UniProt P00736

Length
705 aa
Mass
80.1 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C1r is a modular serine protease zymogen that initiates the classical complement pathway by undergoing Ca2+-regulated autoactivation and subsequently cleaving and activating its sole physiological substrate, C1s, within the C1 macromolecular complex. The proenzyme assembles with C1s into a Ca2+-dependent C1s–C1r–C1r–C1s heterotetramer via CUB1-EGF-CUB2 domain interactions, which binds C1q collagen stems through high-affinity salt bridges between acidic Ca2+-coordinating residues in the C1r CUB domains and reactive lysines (LysB61, LysC58) on C1q (PMID:19473974, PMID:23650384, PMID:29311313). Upon C1q recognition of immune complexes, mechanical disruption of the CCP1–SP interface in the head-to-tail C1r homodimer triggers autolytic cleavage at Arg446–Ile447, generating the active two-chain enzyme whose SP domain exhibits stringent specificity for Gln(P2)–Arg–Ile(P1') in C1s, augmented by CCP2-mediated exosite contacts (PMID:11823416, PMID:11445589, PMID:23589288). Heterozygous missense mutations in C1R cause periodontal Ehlers–Danlos syndrome through constitutive intracellular activation of C1r/C1s and autonomous complement activation rather than loss of complex assembly (PMID:27745832, PMID:31749804).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1976 High

    Establishing that C1r is a serine protease zymogen activated by proteolytic cleavage into disulfide-linked subunits answered the fundamental question of how the classical pathway is enzymatically initiated, and revealed that C1r bridges C1q to C1s in a Ca2+-dependent manner.

    Evidence Biochemical fractionation, SDS-PAGE, radiolabeled binding assays, functional C1 reconstitution

    PMID:1249422 PMID:814163

    Open questions at the time
    • Cleavage site identity unknown
    • Whether activation is autolytic or requires an exogenous protease was unresolved
    • Domain architecture undefined
  2. 1977 High

    Demonstrating that activated C1r cleaves only C1s among tested protein substrates established C1r as a highly specific protease rather than a general trypsin-like enzyme, defining its singular role as the activator of C1s.

    Evidence Amino acid composition, N-terminal sequencing, synthetic ester substrate assays

    PMID:869924

    Open questions at the time
    • Molecular basis for substrate restriction unknown
    • Active-site sequence not yet determined
  3. 1986 High

    Determination of the complete cDNA sequence and domain architecture (CUB1-EGF-CUB2-CCP1-CCP2-SP) resolved how C1r combines recognition/interaction domains with a catalytic module and explained homology with C1s, suggesting gene duplication origin.

    Evidence Full-length cDNA sequencing from liver/HepG2 libraries, confirmed by two independent groups

    PMID:2459702 PMID:3021205 PMID:3030286

    Open questions at the time
    • Functions of individual domains not experimentally tested
    • C1q binding site not mapped
  4. 1994 High

    Reconstitution experiments with truncated C1q fragments showed that Ca2+ suppresses C1r autoactivation intramolecularly, that the C1s–C1r–C1r–C1s tetramer stabilizes the proenzyme, and that intact C1q globular heads plus collagen stems are required to transmit the activation signal — resolving the question of how C1r activation is held in check until target recognition.

    Evidence Spontaneous activation assays, sedimentation, Ca2+ titration, reconstitution with C1q fragments

    PMID:8042996

    Open questions at the time
    • Nature of the C1q-transmitted mechanical signal unknown
    • Ca2+-binding domain not identified
  5. 2001 High

    Domain-deletion and active-site mutagenesis (R446Q, S637A) proved that C1r activation is autolytic rather than requiring an external protease, that autoactivation and C1s cleavage are intrinsic to the SP domain, and that CCP2 enhances C1s cleavage while CCP1 drives dimerization but is dispensable for catalysis.

    Evidence Recombinant domain fragments, site-directed mutagenesis, sedimentation, cleavage assays in E. coli and baculovirus systems

    PMID:11445589 PMID:11673533

    Open questions at the time
    • Structural basis for the CCP1–SP interface restraining activation unknown
    • How dimerization relates to activation in the C1 complex unresolved
  6. 2002 High

    Crystal structures of zymogen and active C1r catalytic region revealed a head-to-tail homodimer where the active site and cleavage site of partner monomers are maximally separated, establishing that mechanical stress disrupting the CCP1–SP interface is the trigger for autoactivation within the C1 complex.

    Evidence X-ray crystallography at 2.9 Å (zymogen S647A mutant) and active CCP2-SP structures

    PMID:11823416 PMID:12429092

    Open questions at the time
    • Source and magnitude of mechanical stress in physiological C1 not measured
    • Full C1 complex structure unavailable
  7. 2010 High

    Mapping C1q-binding sites to acidic Ca2+-ligand residues in C1r CUB1 and CUB2 (high affinity) and C1s CUB1 (lower affinity), and identifying reactive lysines LysB61/LysC58 on C1q stems as their partners, resolved the molecular interface holding the C1 complex together.

    Evidence Site-directed mutagenesis, SPR, ITC, NMR of CUB2, recombinant C1q variants

    PMID:19473974 PMID:20178990 PMID:23650384

    Open questions at the time
    • Stoichiometry of engagement with all six C1q stems not fully resolved
    • Role of partial Ca2+ saturation of CUB2 in vivo unclear
  8. 2013 High

    Phage-display substrate profiling and mutagenesis defined the stringent P2-Gln/P1'-Ile specificity of C1r's active site and demonstrated that CCP domains contribute exosite interactions for efficient C1s cleavage, explaining why C1r is restricted to C1s as its sole natural substrate.

    Evidence Phage display library, C1s activation-site mutagenesis, MD simulation

    PMID:23589288

    Open questions at the time
    • Atomic structure of the C1r–C1s enzyme–substrate complex not determined
    • Whether CCP exosite contacts are essential or merely rate-enhancing unclear
  9. 2016 High

    Discovery that heterozygous C1R mutations cause periodontal Ehlers–Danlos syndrome linked C1r to connective-tissue homeostasis, and subsequent work showed that pEDS variants cause constitutive intracellular C1r/C1s activation and autonomous complement activation rather than loss of C1 complex assembly.

    Evidence Whole-exome sequencing of 19 families, immunofluorescence, patient fibroblast C4-activation assays, overexpression in HEK293T

    PMID:27745832 PMID:31749804

    Open questions at the time
    • How complement activation in connective tissue leads to periodontitis and skin fragility unknown
    • Whether intracellular activation damages the ER or acts extracellularly unresolved
  10. 2018 High

    The crystal structure of the C1r–C1s CUB1-EGF-CUB2 heterodimer revealed an antiparallel L-shaped architecture with Ca2+ at each interface, explaining preferential heterotetramer over homodimer assembly and supporting a model where surface binding separates C1r–C1s pairs to trigger activation.

    Evidence X-ray crystallography of the C1r–C1s interaction domain complex

    PMID:29311313

    Open questions at the time
    • Full-length C1 complex structure still unavailable
    • Dynamics of pair separation upon C1q bending not captured
  11. 2021 Medium

    Beyond complement, CRISPR knockout of C1r in cutaneous SCC cells established a complement-independent tumor-promoting function: C1r drives MMP-1/10/12/13 expression, collagen degradation, ERK1/2–Akt signaling, and xenograft invasion; conversely, in HCC, C1r sequesters CRP to suppress NF-κB/HIF-1α–driven glycolysis, acting as a tumor suppressor.

    Evidence CRISPR KO and siRNA in cSCC lines, mRNA-seq, Western blot, xenograft models; co-IP of CRP–C1r, reporter assays, methylation-specific PCR in HCC

    PMID:31049937 PMID:34756877 PMID:39150096

    Open questions at the time
    • Whether the oncogenic function requires C1r catalytic activity or is scaffold-mediated unknown
    • CRP–C1r interaction awaits structural characterization
    • Single-lab findings for both cancer contexts
  12. 2021 High

    The crystal structure of Borrelia BBK32 bound to activated C1r revealed that pathogen-derived inhibitors block C1r by occluding the S1/S1' substrate-binding subsites, providing atomic-level insight into immune evasion and a template for therapeutic C1r inhibitor design.

    Evidence X-ray crystallography, SAXS, site-directed mutagenesis, SPR, complement assays

    PMID:34759015

    Open questions at the time
    • Whether other microbial C1r inhibitors use the same mechanism unknown
    • No small-molecule inhibitor of C1r yet designed from this template

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete atomic structure of the full C1 complex (C1q bound to the C1s–C1r–C1r–C1s tetramer) is still lacking, and the precise mechanical forces and conformational changes that relay C1q target recognition to C1r autoactivation remain unresolved; additionally, the complement-independent roles of C1r in connective tissue homeostasis and cancer require mechanistic dissection of whether they depend on its catalytic activity or scaffold functions.
  • Full C1 complex structure not determined
  • Force transduction mechanism from C1q to C1r activation site not measured
  • Catalytic vs. non-catalytic roles in pEDS pathogenesis and cancer not distinguished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 4
Partners
C1QAC1QBC1QCC1SCRPSERPING1
Complex memberships
C1 complex (C1q:C1r2:C1s2)C1s-C1r-C1r-C1s tetramer

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1976 C1r functions as a serine protease zymogen that undergoes proteolytic cleavage to become activated; activation converts each 95,000 Da chain into disulfide-linked subunits of 60,000 and 35,000 Da and enables C1r to cleave and activate C1s. C1r also serves as the physical link between C1q and C1s in macromolecular C1, requiring C1q and calcium for binding to sensitized erythrocytes. Biochemical fractionation, SDS-PAGE, radiolabeled binding assays, functional reconstitution of C1 Journal of immunology High 1249422 814163
1976 Activation of C1r by proteolytic cleavage is inhibited by calcium ions (which stabilize the proenzyme form), C1 inactivator (which forms a complex with the light chain of activated C1r), polyanethol sulfonate, and DFP. Activation is triggered when C1r is incorporated into the C1 complex with C1q and aggregated IgG. Biochemical activation assays, SDS-PAGE analysis of cleavage products, inhibitor titration experiments Journal of immunology High 1249422
1977 Activated C1r (C1-r) is a serine protease with a catalytic B chain (~27,000 Da) homologous to the trypsin family of serine proteases; it hydrolyses lysine and tyrosine ester bonds but cleaves only C1s as a protein substrate, demonstrating highly restricted proteolytic specificity. Amino acid composition analysis, N-terminal sequencing, synthetic ester substrate assays The Biochemical journal High 869924
1983 The catalytic B chain of activated C1r contains 242 amino acids with a serine protease active site triad (His-39, Asp-94, Ser-191 by chymotrypsinogen numbering); it lacks the histidine-loop disulfide bridge found in other serine proteases and has five half-cystine residues. Direct amino acid sequence determination by chemical fragmentation and sequencing Biochemistry High 6303394
1985 C1r undergoes autocatalytic (autolytic) activation involving two intermolecular reactions: a DFP-insensitive zymogen-catalyzed step and a DFP-sensitive enzyme-catalyzed step, consistent with activation proceeding through a conformational isomer intermediate before full proteolytic cleavage. Kinetic analysis of activation time-course, DFP inhibition experiments, surface radiolabeling Journal of biochemistry Medium 2987200
1986 The C1r polypeptide precursor of 705 amino acids contains an N-terminal non-catalytic A chain with an EGF-like domain, two pairs of internal repeats (one pair related to C1s N-terminal sequence; the other related to complement factor B and beta2-glycoprotein I), and a C-terminal B chain encoding the serine protease domain homologous to the trypsin family. cDNA sequencing of full-length C1r transcript from human liver and HepG2 libraries Biochemistry High 3021205 3030286
1987 The A chain of activated C1r (446 residues) contains a beta-hydroxyaspartic acid residue at position 150 within an EGF consensus sequence, two carbohydrate chains attached at Asn-108 and Asn-204, and is subdivided by autolytic cleavage into three fragments (alpha, beta, gamma); fragment gamma is disulfide-linked to the catalytic B chain. Complete amino acid sequence determination from autolytic fragments and chemical cleavage peptides The Biochemical journal High 3036070
1988 The human C1R and C1S genes are located on chromosome 12p13 in a closely linked tail-to-tail arrangement separated by approximately 9.5 kb, consistent with gene duplication from a common ancestor; both genes are primarily expressed in liver. cDNA sequencing, genomic DNA blotting, in situ hybridization, RNA blot analysis Proceedings of the National Academy of Sciences High 2459702
1994 Ca2+ ions suppress C1r autoactivation by an intramolecular mechanism involving the Ca2+-binding alpha-region; this inhibitory effect is released in the C1 complex by a signal originating in C1q and transmitted through the C1q/C1r interface. Incorporation of C1r into the C1s-C1r-C1r-C1s tetramer fully stabilizes C1r in proenzyme form, and interaction with intact C1q (but not collagen-like C1q fragments) is required to trigger activation above 25°C. Spontaneous activation assays, sedimentation analysis, Ca2+ titration, reconstitution of C1 with truncated C1q fragments The Biochemical journal High 8042996
1997 The catalytic domain of C1r (CCP1-CCP2-SP) forms a non-covalent homodimer in a head-to-tail arrangement; chemical cross-linking and homology modeling identified an intramonomer cross-link between Lys426 (CCP module V) and the C-terminal Asp688 (SP domain) and an intermonomer cross-link between Gly280 and Glu493, supporting a model where CCP module V interacts with the SP domain on the side opposite to the active site. Chemical cross-linking with EDC, CNBr cleavage, N-terminal sequencing, mass spectrometry, homology modeling Biochemistry High 9174342
1998 The EGF-like module of C1r (residues 123–175) has a well-ordered C-terminal part with canonical EGF fold and a disordered large N-terminal loop between the first two cysteines; Ca2+ at 80 mM did not significantly alter the EGF module structure, indicating Ca2+ binding is mediated by a different mechanism in the full-length protein. NMR structure determination, restrained molecular dynamics calculations Biochemistry High 9477945
2000 In human serum, C1r and C1s are found exclusively in complex with C1q and not with MBL, while MASP-1, MASP-2, and MAp19 are found exclusively with MBL; C1r-deficient serum shows no complement activation on IgG-coated surfaces, confirming that C1r is essential for classical pathway activation via antibody complexes. Gel-permeation chromatography of serum fractions, ELISA, complement activation assays with deficient sera Journal of immunology High 10878362
2001 Autoactivation and C1s cleavage are intrinsic properties of the C1r SP domain alone; the CCP2 module significantly increases proteolytic activity toward C1s and stabilizes the SP domain structure; CCP1 is required for dimer formation but is not required for autoactivation or C1s cleavage. Dimerization of C1r is not a prerequisite for autoactivation. Recombinant expression of domain-deletion fragments in E. coli, renaturation, esterolytic and C1s-cleavage assays, differential scanning calorimetry, sedimentation analysis Journal of immunology High 11673533
2001 Both CCP1/2-SP and CCP2-SP fragments of C1r activate autolytically (confirmed by recovery as two-chain proteases while R446Q and S637A mutants remain single-chain zymogens), proving C1r activation is an autolytic process. CCP1 drives dimerization (5.5 S) but is not required for self-activation; relative C1s-cleavage efficiency is C1r < CCP1/2-SP < CCP2-SP, showing CCP1 is not involved in C1s recognition. Baculovirus expression, site-directed mutagenesis (R446Q, S637A), sedimentation velocity, C1s cleavage assays The Journal of biological chemistry High 11445589
2002 Crystal structure of the zymogen and active catalytic domain (CCP1-CCP2-SP) of C1r shows a homodimer with head-to-tail arrangement where the active site of one monomer and the cleavage site (Arg446) of its partner are at opposite ends, demonstrating that a mechanical stress disrupting the CCP1-SP interface is required to trigger C1r activation in the C1 complex. X-ray crystallography to 2.9 Å (zymogen, S647A mutant) and crystal structures of active CCP2-SP domain The EMBO journal / Structure High 11823416 12429092
2004 C1r-like protein (C1r-LP), a complement-related serine protease, mediates proteolytic cleavage of prohaptoglobin in the endoplasmic reticulum; mutation of the active-site Ser abolished cleavage; substituting Gly for Arg-161 in proHp blocked cleavage; RNAi knockdown of C1r-LP reduced proHp cleavage by up to 45% in HepG2 cells. (Note: This is C1r-LP, a paralog/related protein, not C1r itself, but the abstract identifies it as a distinct gene.) Coexpression in COS-1 cells, active-site mutagenesis, substrate mutagenesis, RNAi knockdown, in vitro cleavage assay with purified proteins Proceedings of the National Academy of Sciences Medium 15385675
2007 Crystal structure of the entire active catalytic region (CCP1-CCP2-SP) of human C1r shows head-to-tail dimer similar to the zymogen; an enzyme-product complex in the crystal lattice reveals a critical S1-P1 salt bridge between Asp631 and Arg446, and intermolecular interaction between CCP2 and SP domain, supporting a split-and-reassembly model for C1r autoactivation without large-scale C1q arm movements. X-ray crystallography of full active catalytic region Molecular immunology High 17996945
2009 The C1q-binding sites of the C1s-C1r-C1r-C1s tetramer reside primarily in the CUB1 and CUB2 modules of C1r (high affinity) and CUB1 of C1s (lower affinity); these sites involve acidic residues that also serve as Ca2+ ligands; the EGF module of C1r (Glu137-Glu-Asp139) does not participate in C1q binding, contrary to earlier models. Altogether six binding sites interact with reactive lysines of C1q stems. Site-directed mutagenesis of C1r and C1s, surface plasmon resonance binding assays The Journal of biological chemistry High 19473974
2010 Ca2+ binding to the CUB2 domain of C1r induces folding from a disordered to a compact structure (Kd ~430 μM); partial Ca2+ saturation of CUB2 in blood provides conformational flexibility required for C1 activation; Ca2+-free CUB2 shows intrinsically disordered character, and Ca2+ significantly suppresses autoactivation of native C1r zymogen. Recombinant domain production, isothermal titration calorimetry, NMR, activation assays with native C1r The Journal of biological chemistry High 20178990
2010 Mass spectrometry-based surface accessibility mapping of the C1r/C1s tetramer in isolation versus in assembled C1 showed that the C1s CUB1-EGF-CUB2 interaction domains, distant in the free tetramer, associate with each other in the C1 complex; the C1s serine protease domain is partly positioned inside the C1q cone in the proenzyme form. Chemical modification of Lys residues, quantitative MS-based accessibility comparison The Journal of biological chemistry High 20592021
2013 C1r demonstrates clear active-site specificity for Gln at P2 and Ile at P1' positions; these residues are present in the physiological C1s activation site, and their removal reduces C1r-mediated C1s activation; introduction of Gln at P2 of the non-substrate MASP-3 enables its efficient cleavage by C1r. The CCP (complement control protein) domains of C1r provide exosite interactions that contribute to efficient C1s cleavage. Phage display library substrate specificity assay, mutagenesis of C1s activation site, MD simulations, structural modeling The Journal of biological chemistry High 23589288
2013 Recombinant C1q variants with mutations at LysB61 and LysC58 in the collagen-like stems show markedly reduced interaction with the C1s-C1r-C1r-C1s tetramer by surface plasmon resonance, demonstrating that LysB61 and LysC58 form key salt bridges with acidic Ca2+ ligands of C1r and C1s CUB domains during C1 assembly. Recombinant C1q expression in HEK293-F cells, site-directed mutagenesis, SPR binding assays, C1r/C1s activation assay Proceedings of the National Academy of Sciences High 23650384
2016 Heterozygous missense or in-frame insertion/deletion mutations in C1R (affecting subunit interfaces or inter-domain hinges) cause periodontal Ehlers-Danlos syndrome; pathogenic C1r variants are associated with intracellular retention and mild ER enlargement, indicating that proper C1r folding and secretion are required for connective tissue homeostasis. Human genetics (whole-exome sequencing of 19 families), immunofluorescence for ER morphology American journal of human genetics High 27745832
2018 Crystal structure of the CUB1-EGF-CUB2 heterodimer of C1r and C1s reveals an antiparallel L-shaped heterodimer with Ca2+ at the interface from each subunit; contacts involving all three domains make heterodimer formation more favorable than homodimer formation, explaining preferential heterotetramer assembly. Structural data support a model where activation is driven by separation of C1r-C1s dimer pairs when C1q binds to a surface. X-ray crystallography of C1r-C1s CUB1-EGF-CUB2 complex Proceedings of the National Academy of Sciences High 29311313
2019 Knockdown of C1r in cutaneous squamous cell carcinoma (cSCC) cells inhibited ERK1/2 and Akt signaling, promoted apoptosis, and suppressed xenograft tumor growth and vascularization in vivo, demonstrating a tumor-cell-autonomous role for C1r in promoting cSCC growth independent of the complement pathway. siRNA knockdown in cSCC cell lines, Western blot for signaling pathways, xenograft tumor model The British journal of dermatology Medium 31049937
2019 C1R mutations causing periodontal EDS result in constitutive intracellular activation of C1r and/or C1s; patient-derived fibroblasts secrete activated C1s and activate externally added C4 in the absence of microbial triggers, demonstrating that pEDS variants cause autonomous complement cascade activation rather than loss of C1 complex assembly. Overexpression in HEK293T cells, Western blot, size exclusion chromatography, SPR, ELISA of patient fibroblast supernatants, C4 activation assay Frontiers in immunology High 31749804
2019 C1r deletion in renal tubular epithelial cells (C1r-null mice) reduced C1s expression, C3 fragment formation, and kidney fibrosis after folic acid injury; in vitro experiments showed C1s expression is dependent on C1r expression; interferon-γ induces co-expression of both proteases. Global C1r knockout mouse, folic acid nephropathy model, immunohistochemistry, in situ hybridization, in vitro renal epithelial cell assays American journal of physiology. Renal physiology Medium 31509012
2021 CRISPR/Cas9 knockout of C1r in cSCC cells decreased proliferation, migration, and invasion through collagen type I, suppressed MMP-1, MMP-10, MMP-12, and MMP-13 production, and reduced collagen degradation and xenograft tumor invasion in vivo, placing C1r upstream of MMP-13-driven matrix remodeling in cSCC. CRISPR/Cas9 knockout, mRNA-seq, Western blot for MMPs, invasion assay through collagen I, xenograft model The Journal of investigative dermatology High 34756877
2021 Crystal structure of the Borrelia burgdorferi BBK32 C-terminal domain in complex with activated human C1r reveals that BBK32 inhibits C1r by occluding the S1 and S1' substrate-binding subsites; B loop-interacting residues of BBK32 also contribute to full inhibitory activity, as validated by site-directed mutagenesis combined with SPR and complement function assays. X-ray crystallography, SAXS, site-directed mutagenesis, SPR, complement activation assays Journal of immunology High 34759015
2021 The C1r2s2 protease heterotetramer stabilizes C1q binding to surface-bound IgG; the contribution of C1r2s2 to C1q-IgG stability differs between IgG subclasses, and hexamer-enhancing IgG mutations improve C1q complex stability both with and without C1r2s2, mechanistically linking the proteases to avid C1 complex assembly on IgG-opsonized surfaces. SPR binding assays, antibody engineering, complement-dependent phagocytosis assays with human neutrophils Proceedings of the National Academy of Sciences High 34155115
2024 In hepatocellular carcinoma, C1r acts as a tumor suppressor; C-reactive protein (CRP) binds to C1r, and when C1r is downregulated (via DNMT1/DNMT3a-mediated promoter methylation), free CRP activates NF-κB signaling, upregulating HIF-1α and increasing glycolysis to promote aggressive HCC behavior. CRISPR/siRNA knockdown, RNA-seq, methylation-specific PCR, co-immunoprecipitation (CRP-C1r interaction), dual-luciferase reporter assay, xenograft model Molecular carcinogenesis Medium 39150096
1999 One active C1r subunit within the C1r homodimer is sufficient for full hemolytic activity of the C1 complex; stabilization of one C1r monomer as a zymogen (R446Q mutant) does not abolish activity when paired with wild-type C1r in a mixed dimer, and C1r monomers exchange between dimers even at 4°C. Baculovirus expression of zymogen-stabilizing C1r mutants, reconstitution hemolytic assay, mixed-dimer experiments Journal of immunology High 9916740

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon. Journal of immunology (Baltimore, Md. : 1950) 270 1541831
1977 The structure and enzymic activities of the C1r and C1s subcomponents of C1, the first component of human serum complement. The Biochemical journal 141 869924
1986 Nucleotide sequence of the cDNA coding for human complement C1r. Biochemistry 129 3021205
1976 Physicochemical and functional characterization of the C1r subunit of the first complement component. Journal of immunology (Baltimore, Md. : 1950) 123 814163
1972 C1r deficiency: an inborn error associated with cutaneous and renal disease. The Journal of clinical investigation 112 4623164
1976 Activation of C1r by proteolytic cleavage. Journal of immunology (Baltimore, Md. : 1950) 108 1249422
2002 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. The EMBO journal 90 11823416
1986 Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r. The Biochemical journal 90 3030286
2000 Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19. Journal of immunology (Baltimore, Md. : 1950) 89 10878362
1998 2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease. Journal of medicinal chemistry 86 9544206
2003 Complete sequencing and expression of three complement components, C1r, C4 and C1 inhibitor, of the classical activation pathway of the complement system in rainbow trout Oncorhynchus mykiss. Immunogenetics 84 14628103
2016 Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement. American journal of human genetics 78 27745832
1970 Deficiency of C1r in human serum. Effects on the structure and function of macromolecular C1. The Journal of experimental medicine 78 4988128
2019 Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma. The British journal of dermatology 71 31049937
2009 Identification of the C1q-binding Sites of Human C1r and C1s: a refined three-dimensional model of the C1 complex of complement. The Journal of biological chemistry 66 19473974
1988 Human genes for complement components C1r and C1s in a close tail-to-tail arrangement. Proceedings of the National Academy of Sciences of the United States of America 60 2459702
2018 Structure of the C1r-C1s interaction of the C1 complex of complement activation. Proceedings of the National Academy of Sciences of the United States of America 56 29311313
2009 Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions. Molecular immunology 56 19477526
2004 Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein. Proceedings of the National Academy of Sciences of the United States of America 53 15385675
1987 Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r. The Biochemical journal 51 3036070
2013 Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites. Proceedings of the National Academy of Sciences of the United States of America 50 23650384
2002 Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism. Structure (London, England : 1993) 47 12429092
1991 Complement components C1r/C1s, bone morphogenic protein 1 and Xenopus laevis developmentally regulated protein UVS.2 share common repeats. FEBS letters 45 2026272
1983 Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r. Biochemistry 45 6303394
2021 C1q binding to surface-bound IgG is stabilized by C1r2s2 proteases. Proceedings of the National Academy of Sciences of the United States of America 44 34155115
1997 A neoepitope-based enzyme immunoassay for quantification of C1-inhibitor in complex with C1r and C1s. Scandinavian journal of immunology 44 9420617
1989 Complement genes C1r and C1s feature an intronless serine protease domain closely related to haptoglobin. Journal of molecular biology 41 2553984
1998 Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family. Biochemistry 40 9477945
2021 C1r Upregulates Production of Matrix Metalloproteinase-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma. The Journal of investigative dermatology 39 34756877
1994 A 100-kDa protein in the C4-activating component of Ra-reactive factor is a new serine protease having module organization similar to C1r and C1s. Journal of immunology (Baltimore, Md. : 1950) 39 8133044
2009 Analysis of human C1q by combined bottom-up and top-down mass spectrometry: detailed mapping of post-translational modifications and insights into the C1r/C1s binding sites. Molecular & cellular proteomics : MCP 37 20008834
1997 Structure and assembly of the catalytic region of human complement protease C1r: a three-dimensional model based on chemical cross-linking and homology modeling. Biochemistry 36 9174342
2007 Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r. Molecular immunology 34 17996945
2001 The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r. Journal of immunology (Baltimore, Md. : 1950) 34 11673533
2001 Assembly and enzymatic properties of the catalytic domain of human complement protease C1r. The Journal of biological chemistry 33 11445589
2011 Clinical presentations and molecular basis of complement C1r deficiency in a male African-American patient with systemic lupus erythematosus. Lupus 30 21784777
1988 Assignment of the complement serine protease genes C1r and C1s to chromosome 12 region 12p13. Human genetics 30 2834284
1985 Primary structure of the A chain of human complement-classical-pathway enzyme C1r. N-terminal sequences and alignment of autolytic fragments and CNBr-cleavage peptides. The Biochemical journal 30 2983658
1971 C1r, subunit of the first complement component: purification, properties, and assay based on its linking role. The Journal of clinical investigation 30 4100685
1992 Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex. Biochemistry 29 1533159
1995 Complement components C1q, C1r/C1s, and C1INH in rheumatoid arthritis. Correlation of in situ hybridization and northern blot results with function and protein concentration in synovium and primary cell cultures. Arthritis and rheumatism 28 7718002
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