Affinage

C5AR1

C5a anaphylatoxin chemotactic receptor 1 · UniProt P21730

Length
350 aa
Mass
39.3 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C5AR1 (CD88) is a seven-transmembrane G protein-coupled receptor for the complement anaphylatoxin C5a that transduces diverse inflammatory, proliferative, and metabolic signals across many cell types. C5a binding engages the receptor's N-terminal extracellular domain and an orthosteric pocket, coupling primarily through Gαi to activate Ras/Raf/MEK/ERK, PI3K/AKT, NF-κB, and PKCζ cascades, while recruiting β-arrestins and undergoing AP2/dynamin-dependent endocytosis facilitated by heterodimerization with C5L2 (C5aR2) (PMID:1847994, PMID:8090790, PMID:24631530, PMID:36806352). Beyond classical plasma membrane signaling that drives neutrophil chemotaxis via an Orai1-dependent, STIM1-independent Ca²⁺ influx pathway (PMID:25912155), C5aR1 operates intracellularly on mitochondrial membranes to redirect ATP production toward reactive oxygen species generation and glycolysis for NLRP3-dependent IL-1β processing, and in lysosomes/endosomes where it assembles a KCTD5/cullin3 complex that switches β-catenin ubiquitination from K48 to K63 linkage, stabilizing β-catenin to promote tumorigenesis (PMID:34932384, PMID:35649359). Cell-type-specific outputs include cardiomyocyte proliferation after injury, neural progenitor symmetric division through PKCζ, platelet-mediated antiangiogenesis via CXCL4 release, podocyte mitochondrial fission through Drp1-S616 phosphorylation, vascular smooth muscle osteogenic transdifferentiation through ER stress-PERK-eIF2α-ATF4, and ferroptosis resistance via ERK-METTL3-m6A stabilization of GPX4 mRNA (PMID:29348261, PMID:28455369, PMID:34099640, PMID:38449312, PMID:37603848, PMID:39368999).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Molecular cloning of C5aR1 established that complement C5a signals through a seven-transmembrane GPCR, resolving the molecular identity of the receptor responsible for neutrophil chemotaxis, degranulation, and superoxide production.

    Evidence Cloning from U937/HL-60 cells, functional reconstitution with ligand binding in COS-7 cells

    PMID:1847994

    Open questions at the time
    • No downstream signaling pathway defined
    • Structural basis of C5a recognition unknown
  2. 1994 High

    Identification of the N-terminal extracellular domain and specific acidic residues as critical for C5a binding, together with mapping of the Gαi-coupled Ras/Raf/MEK/ERK cascade, defined both the ligand-receptor interface and the primary intracellular signaling architecture.

    Evidence Chimeric receptor/mutagenesis binding assays; biochemical kinase cascade mapping in neutrophils with pharmacological inhibitors

    PMID:8090790 PMID:8106386

    Open questions at the time
    • Structural model of C5a–C5aR1 complex not available
    • Role of β-arrestin and receptor internalization unexplored
    • Signaling beyond Ras/MAPK not addressed
  3. 2003 High

    Discovery that C5L2 (C5aR2) binds C5a with high affinity but is G protein–uncoupled due to a DRY motif substitution clarified that the complement anaphylatoxin system employs a second receptor with a fundamentally different signaling logic.

    Evidence Multi-cell-type transfection with radioligand binding, calcium, MAPK, chemotaxis, and internalization assays

    PMID:12899627

    Open questions at the time
    • Whether C5L2 modulates C5aR1 function directly was unknown
    • Physiological role of C5L2 remained undefined
  4. 2009 High

    Demonstration that C5aR1 in dendritic cells inhibits cAMP/PKA while activating PI3K/AKT and NF-κB expanded the receptor's signaling repertoire beyond Ras/MAPK and linked it to adaptive immune regulation.

    Evidence C5aR−/− mouse DCs plus pharmacological antagonism with cAMP, PKA, PI3K, and NF-κB assays

    PMID:19864610

    Open questions at the time
    • Whether these pathways are co-engaged or context-dependent in other cell types was unclear
  5. 2012 High

    BRET and biochemical studies established that C5L2 heterodimerizes with C5aR1 and is required for AP2-dependent receptor internalization and efficient ERK signaling, resolving a key question about how C5aR1 endocytic trafficking is regulated.

    Evidence BRET dimerization assay, β-arrestin and AP2 recruitment, dynamin inhibition, ERK/MEK assays, co-immunoprecipitation

    PMID:23239822 PMID:23268185 PMID:24631530

    Open questions at the time
    • Structural basis of the C5aR1–C5L2 heterodimer interface unknown
    • Whether C5L2 is universally required or cell-type-specific for internalization not settled
  6. 2015 High

    Genetic dissection of Orai1 and STIM1 knockouts in neutrophils revealed that C5aR1 drives Ca²⁺ influx through a STIM1-independent Orai1 pathway, distinguishing C5a-induced calcium signaling from canonical store-operated calcium entry.

    Evidence Orai1−/− and Stim1−/− neutrophils, Ca²⁺ flux, migration assays, in vivo peritonitis/pneumonitis models

    PMID:25912155

    Open questions at the time
    • Molecular mechanism coupling Gαi to Orai1 independently of STIM1 uncharacterized
    • Whether this pathway operates in non-neutrophil cells unknown
  7. 2017 High

    Two studies extended C5aR1 function to non-immune contexts: intracellular C5aR1 on mitochondrial membranes in macrophages redirects metabolism toward ROS and glycolysis for IL-1β production, while C5aR1 on neural progenitors drives symmetric division via PKCζ, establishing that C5aR1 operates both intracellularly and in developmental programs.

    Evidence Mitochondrial fractionation, metabolic flux analysis, macrophage-specific C5ar1 KO, atherosclerosis model; mouse embryonic imaging, human ESC-derived neural progenitors, PKCζ pathway analysis, MRI

    PMID:28455369 PMID:34932384

    Open questions at the time
    • How C5aR1 is targeted to mitochondrial membranes unknown
    • Identity of the intracellular C5 convertase not fully characterized
    • Whether intracellular C5aR1 signals through Gi on mitochondria not confirmed
  8. 2018 High

    Cross-species genetic studies showed C5aR1 is required for cardiomyocyte proliferation and cardiac regeneration after injury, broadening its role to tissue repair beyond inflammation.

    Evidence C5aR1 knockout mice, zebrafish, and axolotl cardiac resection models with cardiomyocyte proliferation quantification

    PMID:29348261

    Open questions at the time
    • Downstream proliferative signaling pathway in cardiomyocytes not defined
    • Whether complement-independent ligands can activate C5aR1 in this context unknown
  9. 2019 High

    Identification of C5apep as a G protein–biased agonist at C5aR1 that fully activates Gαi/ERK but only partially recruits β-arrestin established ligand-dependent functional selectivity, while intravital imaging showed C5aR2-mediated transcytosis delivers C5a to activate C5aR1 on neutrophils in vivo.

    Evidence Multi-assay pharmacological profiling of C5apep vs C5a; intravital microscopy with C5aR2−/− mice and fluorescent C5a

    PMID:31036565 PMID:31076525

    Open questions at the time
    • Structural basis for biased signaling at C5aR1 not yet resolved
    • Whether C5aR2 transcytosis occurs in tissues beyond joints unknown
  10. 2021 High

    Platelet-specific C5aR1 deletion revealed an unexpected antiangiogenic role: C5a-C5aR1 triggers preferential release of CXCL4 from platelets, inhibiting endothelial tube formation and in vivo vascularization.

    Evidence Platelet-specific C5aR1 conditional KO, Matrigel assays, CXCL4 ELISA, in vivo vascularization models

    PMID:34099640

    Open questions at the time
    • Mechanism of selective CXCL4 granule release over other platelet granule contents unknown
    • Relevance to tumor angiogenesis not directly tested
  11. 2022 High

    Discovery that intracellular C5aR1 in colonic cancer cells assembles a KCTD5/cullin3/Roc-1 complex to switch β-catenin ubiquitination from K48 to K63 linkage, stabilizing β-catenin, revealed a non-canonical intracellular oncogenic mechanism independent of classical GPCR signaling.

    Evidence Co-IP of C5aR1–KCTD5/cullin3/Roc-1 complex, K48 vs K63 ubiquitin chain analysis, C5aR1 KO, xenograft tumors

    PMID:35649359

    Open questions at the time
    • Whether C5aR1 directly contacts KCTD5 or acts through an adaptor unknown
    • Generalizability beyond colorectal cancer not established
  12. 2023 High

    Cryo-EM structures of the C5a–C5aR1–Gi complex with multiple agonists resolved the molecular basis of ligand recognition and identified unusual TM7/helix 8 rearrangements that provide a framework for understanding biased signaling and designing selective therapeutics.

    Evidence Cryo-EM at near-atomic resolution with three different ligands, site-directed mutagenesis, functional pharmacological validation

    PMID:36806352 PMID:37169960

    Open questions at the time
    • No structure of C5aR1 in β-arrestin–bound or C5L2-complexed state
    • Structural basis of intracellular C5aR1 signaling unknown
  13. 2023 High

    Multiple 2023 studies established new cell-type-specific C5aR1 effector pathways: NET-dependent lung immunopathology in COVID-19, ER stress-driven vascular calcification through PERK-eIF2α-ATF4-CREB3L1, and platelet-to-macrophage C5a signaling circuits promoting colorectal cancer.

    Evidence C5aR1 KO and antagonist in SARS-CoV-2 mouse model; VSMC calcification with PERK/ATF4/CREB3L1 pathway dissection and CKD mouse model; platelet–macrophage co-culture with ChIP and AOM/DSS model

    PMID:37064877 PMID:37104043 PMID:37603848

    Open questions at the time
    • Whether NET formation is a direct or indirect consequence of C5aR1 activation on neutrophils not resolved
    • Upstream triggers of C5 production in the vascular calcification context not characterized
  14. 2024 High

    C5aR1 was linked to two additional effector mechanisms: Drp1-S616 phosphorylation driving mitochondrial fission in podocytes contributing to lupus nephritis, and ERK-METTL3-m6A methylation stabilizing GPX4 mRNA to inhibit ferroptosis in glioblastoma.

    Evidence siRNA knockdown in podocytes with Drp1 phosphorylation and mitochondrial morphology, lupus mouse model; C5aR1 knockdown with METTL3/m6A/GPX4 assays and intracranial xenografts

    PMID:38449312 PMID:39368999

    Open questions at the time
    • Whether Drp1-S616 phosphorylation is directly mediated by a C5aR1-activated kinase or indirect not established
    • Whether the METTL3-GPX4 axis operates downstream of intracellular vs surface C5aR1 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how C5aR1 is targeted to intracellular compartments (mitochondria, lysosomes), the structural basis of C5aR1–C5L2 heterodimerization and β-arrestin-biased signaling conformations, the identity and regulation of the intracellular C5 convertase in non-cancer cells, and whether the diverse cell-type-specific effector pathways converge on shared proximal signaling nodes.
  • No structural model of C5aR1–C5L2 heterodimer
  • Mechanism of intracellular C5aR1 trafficking to mitochondria uncharacterized
  • No unified model for how C5aR1 selects among diverse downstream effector pathways

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2 GO:0005739 mitochondrion 1 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ARRB1C5AR2CUL3DRP1KCTD5METTL3ORAI1TLR2
Complex memberships
C5aR1–C5L2 heterodimerC5aR1–Gi complexC5aR1–KCTD5/cullin3/Roc-1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 C5aR1 (CD88) was cloned from U937 and HL-60 cells and identified as a G protein-coupled receptor with seven transmembrane domains that mediates high-affinity binding of C5a anaphylatoxin, driving chemotaxis, granule enzyme release, superoxide anion production, and upregulation of MAC-1 and CR1 on neutrophils. Molecular cloning, expression in COS-7 cells with ligand binding assay Nature High 1847994
1994 The N-terminal extracellular domain of C5aR1 is required for both plasma membrane trafficking and high-affinity C5a binding; specifically, negatively charged residues (Asp) within the first 13 N-terminal residues are critical for ligand binding. Chimeric receptor construction between C5aR and FPR/FPRH, site-directed mutagenesis, cell surface expression and binding assays The Journal of biological chemistry High 8106386
1994 C5aR1 signals through inhibitory G proteins (Gi) in neutrophils to activate a MAP kinase cascade involving Ras, B-Raf, Raf-1, MEK-1, and MAP kinase; B-Raf and Raf-1 activation involves both protein kinase C-dependent and -independent pathways, and is inhibited by protein kinase A (cAMP elevation). Biochemical signal transduction mapping in human neutrophils using kinase assays, GTP exchange measurements, and pharmacological inhibitors Proceedings of the National Academy of Sciences of the United States of America High 8090790
2003 C5L2 (C5aR2/GPR77) binds C5a with high affinity but is obligately uncoupled from heterotrimeric G proteins due to a Leu-for-Arg substitution in the DRY motif at the end of transmembrane segment 3; C5L2 does not mediate MAP kinase activation, calcium flux, or chemotaxis, is weakly phosphorylated after C5a binding, lacks significant internalization, and does not bind C3a or C4a. Transfection into multiple cell types, radioligand binding, calcium flux, MAP kinase assays, chemotaxis assays, phosphorylation assays, internalization assays, gene expression microarray Biochemistry High 12899627
2009 C5aR1 signaling in dendritic cells inhibits cAMP production and protein kinase A activity while activating PI3K/AKT and NF-κB pathways, resulting in upregulation of MHC class II, B7.2, IL-12p70, and enhanced capacity for allospecific T cell stimulation. C5aR-/- mice DCs, C5aR antagonist treatment, cAMP assay, PKA activity assay, PI3K/AKT and NF-κB pathway analysis, ELISA, flow cytometry Journal of immunology High 19864610
2012 C5aR1 and C5L2 form homo- and heterodimers in cells (BRET assay); C5L2 is required for optimal C5a-mediated C5aR1 internalization via AP2-dependent endocytosis and subsequent ERK signaling, as C5aR1 alone can recruit β-arrestin1 but cannot mediate AP2 recruitment or receptor internalization without C5L2. BRET assay for dimerization, dynamin inhibitor (dynasore) treatment, β-arrestin1 and AP2 recruitment assays, ERK/MEK signaling assays, co-immunoprecipitation Cellular signalling High 24631530
2012 C5L2 physically interacts with C5aR1 and β-arrestin to negatively regulate C5aR1 signaling in an anti-inflammatory manner in some disease contexts, while in other contexts C5L2 stimulation causes HMGB1 release. Co-immunoprecipitation, β-arrestin recruitment assay, in vivo sepsis models FASEB journal Medium 23239822
2012 C5L2 and C5aR1 form homo- and heterodimers (BRET) in adipocytes; in adipocytes, C5a stimulation causes C5L2 internalization with perinuclear colocalization with C5aR1, and ASP (C5L2 ligand) but not C5a induces Akt phosphorylation and fatty acid uptake, indicating differential signaling based on ligand. BRET assay, confocal microscopy, Akt phosphorylation assay, fatty acid uptake/esterification assay Cellular signalling Medium 23268185
2013 C5aR1 ligation with C5a triggers appearance of extracellular histones (H3, H4) in bronchoalveolar lavage fluid during acute lung injury, with neutrophil depletion markedly reducing H4 presence; C5aR1- and C5L2-dependent histone release is required for full development of acute lung injury. Three mouse models of acute lung injury, antibody neutralization of histones, neutrophil depletion, bronchoalveolar lavage analysis FASEB journal Medium 23982144
2017 In macrophages, intracellular C5a is generated from intracellularly synthesized C5 via an intracellular C5 convertase; C5aR1 signaling on mitochondrial membranes upon cholesterol crystal sensing shifts ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis, promoting IL-1β production at both transcriptional and pro-IL-1β processing levels. Intracellular complement detection, mitochondrial fractionation, metabolic flux analysis, C5ar1 macrophage-specific knockout mice, atherosclerosis model, cell-permeable C5aR1 antagonist, NLRP3 inflammasome assays Science immunology High 34932384
2017 C5aR1 signaling in embryonic neural progenitor cells drives proliferation and symmetric division via atypical protein kinase C ζ (PKCζ); C5aR1 is expressed on the apical surface of neural progenitors, and its inhibition reduces proliferation, disrupts cell polarity, and leads to brain developmental abnormalities and behavioral deficits. In vivo mouse embryonic imaging, human embryonic stem cell-derived neural progenitors, C5aR1 inhibition, PKCζ pathway analysis, MRI, behavioral testing The Journal of neuroscience High 28455369
2018 C5aR1 interacts physically with Toll-like receptor 2 (TLR2) in osteoblasts (co-immunoprecipitation); this C5aR1-TLR2 interaction converges on p38 MAPK activation to upregulate CXCL10 expression, an osteoclastogenic chemokine. Whole-genome microarray, co-immunoprecipitation, p38 MAPK phosphorylation assay, CXCL10 expression analysis Journal of cellular and molecular medicine Medium 30247799
2018 C5aR1 activation promotes cardiomyocyte proliferation after cardiac injury and is required for cardiac regeneration; genetic deletion of C5aR1 diminishes the cardiomyocyte proliferative response to heart injury in zebrafish, axolotls, and mice. Cross-species transcriptomic screen, C5aR1 genetic knockout mice, C5aR1 pharmacological inhibition, cardiomyocyte proliferation quantification after apical resection Circulation High 29348261
2019 C5aR2 on endothelial cells transports C5a from the tissue into the vessel lumen in a transcytosis-like fashion, enabling C5a to then activate C5aR1 on neutrophils to initiate neutrophil arrest and entry into inflamed tissue during immune complex-induced arthritis. Intravital microscopy in live mice, C5aR2-/- mice, fluorescently labeled C5a transport assay, neutrophil arrest and diapedesis quantification Science immunology High 31076525
2019 C5apep (C-terminal fragment of C5a) acts as a full agonist at C5aR1 for Gαi coupling and ERK1/2 phosphorylation but shows partial agonism for β-arrestin recruitment and receptor endocytosis, revealing functional bias at C5aR1; neutrophil migration is substantially lower with C5apep compared with C5a despite both being pertussis toxin-sensitive. cAMP assay, ERK1/2 phosphorylation, β-arrestin recruitment assay, receptor internalization assay, neutrophil migration assay, pertussis toxin treatment The Journal of biological chemistry High 31036565
2021 C5aR1 on platelets mediates an antiangiogenic mechanism: C5a activates platelet C5aR1 to preferentially trigger release of the antiangiogenic chemokine CXCL4 (PF4), thereby inhibiting endothelial cell migration and tube formation; platelet-specific C5aR1 deletion leads to a proangiogenic phenotype with increased collateralization and capillarization. C5ar1-/- mice, platelet-specific C5aR1 deletion, Matrigel and in vitro tube formation assays, CXCL4 ELISA, in vivo vascularization models Nature communications High 34099640
2022 Intracellular C5a in colonic cancer cells is generated by cathepsin D (CTSD)-mediated cleavage of C5 in lysosomes/endosomes; intracellular C5aR1 then assembles a complex with KCTD5/cullin3/Roc-1 and β-catenin, switching β-catenin polyubiquitination from K48 to K63 linkage, thereby stabilizing β-catenin and promoting colorectal tumorigenesis. Intracellular C5 and C5a detection, co-immunoprecipitation of C5aR1-KCTD5/cullin3/Roc-1 complex, ubiquitination assay distinguishing K48 vs K63 linkage, C5aR1 knockout/pharmacological blockade, xenograft tumor models Cell reports High 35649359
2023 Cryo-EM structures of activated C5aR1-Gi protein complex bound to C5a, hexapeptidic agonist C5apep, and G protein-biased agonist BM213 reveal the landscape of C5a-C5aR1 interaction, a common orthosteric ligand recognition motif, and unusual conformational changes in transmembrane domain 7 and helix 8 upon agonist binding; mutagenesis studies including C5aR1-I116A mutant define framework for biased signaling. Cryo-electron microscopy, site-directed mutagenesis, cell-based pharmacological assays (G protein coupling, β-arrestin recruitment) Cell research High 36806352
2023 Cryo-EM structures of C5a-bound C5aR1 in complex with Gi reveal a unique pocket topology and conserved recognition pattern distinct from chemokine receptors, with structural templates validated by mutagenesis. Cryo-electron microscopy, mutagenesis analysis Nature chemical biology High 37169960
2023 C5aR1 signaling drives neutrophil extracellular trap (NET)-dependent immunopathology in COVID-19 lung injury; genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in SARS-CoV-2-infected K18-hACE2 transgenic mice, and this was mechanistically linked to NETs formation. Genetic C5aR1 knockout, pharmacological C5aR1 antagonist, SARS-CoV-2 infection mouse model, NETs quantification, lung histopathology The Journal of clinical investigation High 37104043
2024 The C5a-C5aR1 axis in podocytes promotes mitochondrial fission by upregulating Drp1-S616 phosphorylation; C5aR1 knockdown by siRNA suppresses C5a-induced Drp1-S616 phosphorylation and mitochondrial fission, and in vivo C5aR1 inhibition reduces Drp1-S616 phosphorylation in podocytes and protects against lupus nephritis. siRNA knockdown of C5aR1 in podocytes, Drp1-S616 phosphorylation assay, mitochondrial morphology analysis, lupus-prone mouse model with C5aR1 inhibitor, proteinuria measurement Molecular therapy High 38449312
2024 Intracellular C5aR1 in glioblastoma cells inhibits ferroptosis by stabilizing GPX4 through METTL3-dependent m6A methylation; mechanistically, C5aR1 activates ERK1/2 signaling, which increases METTL3 protein abundance and thereby stabilizes m6A modifications on GPX4 mRNA. C5aR1 knockdown, GPX4 expression and stability assays, METTL3 m6A methylation assay, ERK1/2 inhibition, intracranial xenograft mouse model with PMX205 Cell death & disease High 39368999
2011 C5aR1 on mast cells mediates C5a-induced Ca2+ mobilization; the C5aR1 antagonist PMX-53 (at higher concentrations) also acts as an agonist for MrgX2 on mature mast cells, with Trp and Arg residues required for both CD88 antagonism and MrgX2 agonism; C5a does not use MrgX1 or MrgX2 for mast cell degranulation. Ca2+ mobilization assay, degranulation assay in LAD2 and CD34+ mast cells, RBL-2H3 cells stably expressing MrgX1 or MrgX2, alanine substitution of PMX-53 residues Molecular pharmacology High 21441599
2015 Orai1 is a key signal mediator of C5aR1 activation in neutrophils; Orai1-deficient neutrophils display defective C5a-induced Ca2+ influx and migration despite normal STIM1-dependent store-operated Ca2+ entry (SOCE), identifying a STIM1-independent Orai1 pathway downstream of C5aR1. Orai1-/- and Stim1-/- neutrophils, Ca2+ flux assay, migration assay, in vivo peritonitis and pneumonitis models, bone marrow chimeras European journal of immunology High 25912155
2023 C5a-C5aR1 axis induces endoplasmic reticulum stress via the PERK-eIF2α-ATF4 pathway in vascular smooth muscle cells; ATF4 activates CREB3L1, which promotes COL1α1 expression and drives osteogenic transdifferentiation contributing to vascular calcification; PMX53 (C5aR1 antagonist) reduces calcification in vivo and in vitro. In vitro VSMCs calcification model, ER stress pathway analysis (PERK, eIF2α, ATF4, CREB3L1 phosphorylation/expression), chronic kidney disease mouse model, PMX53 treatment Cardiovascular research High 37603848
2023 Platelets signal to tumor-associated macrophages through CD62P (P-selectin) binding to PSGL-1 on macrophages, activating JNK/STAT1 signaling that promotes C5 transcription and C5a release, which then activates C5aR1 on macrophages to drive a pro-tumor phenotype in colorectal cancer. Co-culture experiments, PSGL-1/JNK/STAT1 pathway analysis, ChIP assay, dual-luciferase reporter, C5aR1 inhibition, AOM/DSS mouse model Theranostics High 37064877
1998 C5aR1 (CD88) is expressed on human mesangial cells; C5a binding to C5aR1 upregulates transcription factors AP-1 (but not NF-κB) and CREB, and induces c-jun and c-fos mRNA expression; C5adesArg does not produce this effect. RT-PCR, Western blot, immunostaining, transcription factor activity assay (AP-1, CREB, NF-κB), anti-C5aR blocking antibody Journal of immunology Medium 9605171
2010 C5a binding to C5aR1 promotes migration, proliferation, cell cycle progression into G2/M phase, and tube formation in human microvascular endothelial cells (HMEC-1); all these effects are blocked by the specific C5aR1 antagonist W-54011; C5a also promotes angiogenesis in vivo in a Matrigel plug assay. DNA synthesis assay, flow cytometry cell cycle analysis, Chemotaxicell migration assay, collagen gel tube formation assay, Matrigel plug in vivo assay, pharmacological C5aR1 blockade Inflammation research Medium 20217457
2013 C5aR1 activation in hepatic stellate cells (HSC) upregulates fibronectin mRNA five-fold; IL-6 (as a main inflammatory mediator) induces de novo expression of functional C5aR1 on hepatocytes in vitro and in vivo, while unstimulated hepatocytes lack C5aR1. Quantitative RT-PCR, FACS, immunohistochemistry, functional C5a response assay, IL-6 stimulation in vitro and in vivo Histology and histopathology Medium 12507307

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The chemotactic receptor for human C5a anaphylatoxin. Nature 605 1847994
2020 Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. Nature 428 32726800
1994 C5A anaphylatoxin and its seven transmembrane-segment receptor. Annual review of immunology 339 8011297
2007 Function, structure and therapeutic potential of complement C5a receptors. British journal of pharmacology 317 17603557
2008 Functional roles for C5a receptors in sepsis. Nature medicine 310 18454156
2013 C5a receptor (CD88) blockade protects against MPO-ANCA GN. Journal of the American Society of Nephrology : JASN 277 24179165
2011 Inhibiting the C5-C5a receptor axis. Molecular immunology 240 21549429
2003 C5L2, a nonsignaling C5A binding protein. Biochemistry 211 12899627
2018 Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerging microbes & infections 186 29691378
2012 C3a and C5a promote renal ischemia-reperfusion injury. Journal of the American Society of Nephrology : JASN 182 22797180
2013 Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 181 23982144
2002 Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N. Microbiology and immunology 177 11939578
2012 C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 169 23239822
2002 Generation of C5a by phagocytic cells. The American journal of pathology 165 12414531
2002 Increased C5a receptor expression in sepsis. The Journal of clinical investigation 155 12093893
2009 Complement component 5a (C5a). The international journal of biochemistry & cell biology 146 19464229
2021 Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation. Science immunology 123 34932384
2008 Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2. Immunology and cell biology 121 18227853
2010 The harmful role of c5a on innate immunity in sepsis. Journal of innate immunity 118 20588003
1994 Mapping of the C5a receptor signal transduction network in human neutrophils. Proceedings of the National Academy of Sciences of the United States of America 111 8090790
2009 Dendritic cell function in allostimulation is modulated by C5aR signaling. Journal of immunology (Baltimore, Md. : 1950) 104 19864610
2012 Local complement-targeted intervention in periodontitis: proof-of-concept using a C5a receptor (CD88) antagonist. Journal of immunology (Baltimore, Md. : 1950) 101 23089394
2015 The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 25904802
2009 Functions of C5a receptors. Journal of molecular medicine (Berlin, Germany) 87 19189071
2022 Intracellular complement C5a/C5aR1 stabilizes β-catenin to promote colorectal tumorigenesis. Cell reports 85 35649359
2004 Role of C5a-C5aR interaction in sepsis. Shock (Augusta, Ga.) 84 14676676
2010 Microglial C5aR (CD88) expression correlates with amyloid-beta deposition in murine models of Alzheimer's disease. Journal of neurochemistry 81 20132482
2018 Blockade of the Complement C5a/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by CXCL16-mediated Effects. American journal of respiratory and critical care medicine 79 29327939
2016 Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 71 26956419
2019 The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy. Frontiers in immunology 70 31379815
2011 PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Molecular pharmacology 69 21441599
2013 Complement mediated renal inflammation induced by donor brain death: role of renal C5a-C5aR interaction. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 66 23398742
2017 The Controversial C5a Receptor C5aR2: Its Role in Health and Disease. Journal of immunology research 65 28706957
1994 The NH2-terminal region of C5aR but not that of FPR is critical for both protein transport and ligand binding. The Journal of biological chemistry 65 8106386
2019 Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV. Viruses 63 30634407
2017 Complement C5aR1 Signaling Promotes Polarization and Proliferation of Embryonic Neural Progenitor Cells through PKCζ. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 28455369
2012 New developments in C5a receptor signaling. Cell health and cytoskeleton 63 23576881
1985 Model structure for the inflammatory protein C5a. Science (New York, N.Y.) 62 3992245
2018 Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration. Circulation 61 29348261
2012 New insights for C5a and C5a receptors in sepsis. Frontiers in immunology 61 23233853
2019 Critical role of C5a in sickle cell disease. American journal of hematology 60 30569594
2019 The C5a/C5aR1 axis promotes progression of renal tubulointerstitial fibrosis in a mouse model of renal ischemia/reperfusion injury. Kidney international 60 31029505
2023 Mechanism of activation and biased signaling in complement receptor C5aR1. Cell research 58 36806352
2022 Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19. Frontiers in immunology 53 35309299
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