C3
Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients.
Function
C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.
Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity).
It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.
Acylation stimulating protein: adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).
Biological Process
Amyloid-beta clearance Source: ARUK-UCL
Cell surface receptor signaling pathway involved in cell-cell signaling Source: Ensembl
Cellular protein metabolic process Source: Reactome
Complement activation Source: BHF-UCL
Complement activation, alternative pathway Source: Reactome
Complement activation, classical pathway Source: UniProtKB-KW
Complement-dependent cytotoxicity Source: Ensembl
Complement-mediated synapse pruning Source: ARUK-UCL
Fatty acid metabolic process Source: UniProtKB-KW
G protein-coupled receptor signaling pathway Source: Reactome
Immune response Source: ProtInc
Inflammatory response Source: UniProtKB-KW
Neuron remodeling Source: ARUK-UCL
Neutrophil degranulation Source: Reactome
Oviduct epithelium development Source: Ensembl
Positive regulation of activation of membrane attack complex Source: Ensembl
Positive regulation of angiogenesis Source: Ensembl
Positive regulation of apoptotic cell clearance Source: BHF-UCL
Positive regulation of glucose transmembrane transport Source: UniProtKB
Positive regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
Positive regulation of lipid storage Source: UniProtKB
Positive regulation of phagocytosis, engulfment Source: ARUK-UCL
Positive regulation of protein phosphorylation Source: UniProtKB
Positive regulation of receptor-mediated endocytosis Source: ARUK-UCL
Positive regulation of type IIa hypersensitivity Source: Ensembl
Positive regulation of vascular endothelial growth factor production Source: BHF-UCL
Post-translational protein modification Source: Reactome
Purinergic nucleotide receptor signaling pathway Source: Reactome
Regulation of complement activation Source: Reactome
Regulation of immune response Source: Reactome
Regulation of triglyceride biosynthetic process Source: UniProtKB
Response to bacterium Source: Ensembl
Signal transduction Source: ProtInc
Vertebrate eye-specific patterning Source: ARUK-UCL
Cellular Location
Secreted
Involvement in disease
Complement component 3 deficiency (C3D): A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.
Macular degeneration, age-related, 9 (ARMD9): A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Hemolytic uremic syndrome atypical 5 (AHUS5): An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.
Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.
PTM
C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other proteases produce other fragments such as C3d or C3g. C3a is further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by insulin and dietary chylomicrons.
(Microbial infection) C3 is cleaved by Staphylococcus aureus aureolysin; this cleavage renders C3a and C3b inactive. C3b is rapidly degraded by host factors CFH and CFI preventing its deposition on the bacterial surface while C3a is further inactivated by aureolysin.
Phosphorylated by FAM20C in the extracellular medium.
Loading...
Datasheet