Gene Ontology annotation through association of InterPro records with GO terms
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Fifth component of human complement: purification from plasma and polypeptide chain structure.
Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils.
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C5a acts as a potent non-chemokine chemoattractant for human neutrophils, distinct from CXC chemokines such as IL-8, ENA-78, and GRO-alpha.
"If neutrophils were treated with fMLP, IL-8, C5a, ENA-78, or GRO-alpha just before perfusion over this HUVEC, transmigration, but not adhesion, was abolished."
An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice.
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C5a induces CCL2 and VEGF production by retinal pigment epithelial and choroidal endothelial cells.
"RPE or choroidal endothelial production of Ccl-2 induced by complement C5a and IgG may mediate choroidal macrophage infiltration into aged wild-type choroids."
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Accumulation of C5a induces VEGF production by retinal pigment epithelial cells, promoting choroidal neovascularization.
"Impaired macrophage recruitment may allow accumulation of C5a and IgG, which induces vascular endothelial growth factor (VEGF) production by RPE, possibly mediating development of CNV."
Drusen complement components C3a and C5a promote choroidal neovascularization.
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C5a induces VEGF expression in retinal pigment epithelial cells in vitro and in vivo, promoting choroidal neovascularization.
"Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo."
Large-scale proteomics and phosphoproteomics of urinary exosomes.
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LC-MS/MS proteomic profiling of human urinary exosomes identified 1,132 proteins including C5.
"Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously"
Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation.
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CFHR1 binds to C5 and C5b6 and inhibits C5 convertase activity and terminal MAC assembly.
"Here we identify CFHR1 as a novel inhibitor of the complement pathway that blocks C5 convertase activity and interferes with C5b surface deposition and MAC formation."
Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex.
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Crystal structure of human C5 in complex with the C3b homologue cobra venom factor (CVF) reveals how C5 is recognized by complement convertases.
"We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution."
Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9.
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Cleavage of C5 into C5a and C5b exposes a labile C6-binding site on C5b that nucleates assembly of the membrane attack complex, and C5 lacks the internal thioester present in other C3/alpha2-macroglobulin family members.
"Upon complement activation, C5 is cleaved into C5a and C5b by the C5 convertase. C6 then captures a labile binding site in C5b (half-life: 2 min)"
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C5 lacks the internal reactive thioester present in the TED domain of C3 and alpha-2-macroglobulin family proteins.
"C5 lacks the prototypical thioester present in this domain in other members of the C3/α2-macroglobulin protein family."
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
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Shotgun proteomics of EPS-urine exosomes detected complement activation proteins including C5.
"Global GO enrichment analyses of these 127 proteins revealed that the most significant functional categories were related to inflammation: immune response (27 proteins), response to wounding (21 proteins), defense response (19 proteins), inflammatory response (14 proteins) and complement activation (7 proteins) (Figure 1B)."
A proteome-scale map of the human interactome network.
CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.
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Cryo-EM structures of the open and closed human membrane attack complex reveal how C5b6 acts as a platform to direct assembly of the C5b-9 pore.
"CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant β-barrel whose structure is supported by a glycan scaffold."
A reference map of the human binary protein interactome.
Mechanism of activation and biased signaling in complement receptor C5aR1.
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Cryo-EM structures of C5aR1 in complex with C5a illustrate how the C5a anaphylatoxin activates C5aR1 and downstream G protein and beta-arrestin signaling pathways.
"The complement fragment C5a is one of its important effector components and exerts diverse physiological functions through activation of the C5a receptor 1 (C5aR1) and associated downstream G protein and β-arrestin signaling pathways."
Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.
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Cryo-EM structures of Gi-coupled C5aR1 bound to C5a define selective activation of C5aR1 signaling by the C5a anaphylatoxin.
"The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses."
Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.
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Structural and functional analysis defines how the terminal complement anaphylatoxin C5a binds and activates the GPCR C5aR1.
"The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1."
Granzyme K activates the entire complement cascade.
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Granzyme K cleaves C4 and C2 to form C3 and C5 convertases that cleave C5 into C5a and C5b, generating the C5a anaphylatoxin and the membrane attack complex.
"The nascent C4b and C2b fragments form a C3 convertase that cleaves C3, enabling the assembly of a C5 convertase that cleaves C5. The resulting convertases generate all the effector molecules of the complement cascade: the anaphylatoxins C3a and C5a, the opsonins C4b and C3b, and the membrane attack complex."
Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a.
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Establishes the complete 74-residue amino acid sequence and carbohydrate attachment of human C5a anaphylatoxin cleaved from serum C5.
"The C5a molecule is one of two spasmogenic fragments (i.e. C3a and C5a) released from serum components C3 and C5 during complement activation."
The amino terminus of the human C5a receptor is required for high affinity C5a binding and for receptor activation by C5a but not C5a analogs.
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Establishes the two-site binding model in which the C5a core binds the C5aR1 N-terminal domain and the C5a C-terminal 8 residues engage the receptor transmembrane domain to trigger activation.
"The binding domain of the human C5a receptor consists of two distinct and physically separable subsites. One of these sites binds the C-terminal 8 amino acids of C5a and is as yet undefined, while the second site lies in the N terminus of the receptor and interacts with the core of C5a."
C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway.
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C5a acts as a potent chemotaxin for human mast cells via a pertussis toxin-sensitive Gi-coupled receptor signaling pathway.
"Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1."
In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins.
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Human C5aR1 expressed in Xenopus oocytes responds robustly to its cognate ligand C5a via a G protein-coupled signaling cascade.
"Oocytes expressing the anaphylatoxin C3a and C5a receptors responded to both agonists, in each case the response to the cognate ligand was substantially more robust than the response elicited by the other anaphylatoxin."
TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis.
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Detects the secreted C5a anaphylatoxin ligand in the cerebrospinal fluid of human patients with infectious meningitis.
"The finding of TNF-alpha-mediated C5aR expression on neurons in experimental Listeria meningitis and the detection of the ligand, C5a, in the cerebrospinal fluid of human patients with infectious meningitis present new directions in the investigation of the pathophysiologic sequelae leading to secondary brain damage."
Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke.
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Human bronchial epithelial cells express the C5a receptor (CD88/C5aR1) and respond to C5a stimulation by releasing IL-8.
"Control (untreated) HBECs responded to C5a (50 nM) by releasing the proinflammatory cytokine IL-8 at low but significant levels."
C5b:C6:C7 translocates to the plasma membrane
Formation of soluble VTN:C5b-C9
CD59 inhibits MAC formation
Vitronectin (VTN) binds to C5b:C6:C7
C5a receptor binds C5a anaphylatoxin
Liganded Gi-activating GPCR acts as a GEF for Gi
The Ligand:GPCR:Gi complex dissociates
Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
Clusterin binds C5b-C7, C8, C9
Thrombin, ELANE cleave C5
CPN, CPB2 cleave C3a, C5a
C5AR2 binds anaphylatoxins and thier desArginated derivatives