C3
GeneName
C3
Summary
C3, also known as complement C3, C3d, or CIII, is a 187 kDa glycoprotein that plays a central role in the complement system, which is part of the immune response. It is primarily expressed in the blood and is secreted into the extracellular space, where it can be found in various cellular compartments, including the plasma membrane and extracellular exosomes. C3 is involved in complement activation through both the classical and alternative pathways, facilitating processes such as opsonisation, inflammation, and cell lysis. Additionally, it participates in B cell activation and has roles in amyloid-beta clearance and neuron remodeling, contributing to synaptic pruning and the regulation of immune responses.
Importance
C3 is relevant to: - Immune system research, particularly in understanding complement-mediated immunity and inflammation - Neurodegenerative diseases due to its involvement in amyloid-beta clearance and synapse pruning - Autoimmune disorders, where dysregulation of complement activation can contribute to pathology - Cancer biology, as it influences tumour microenvironments through immune modulation and angiogenesis
Top Products
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Abcam Product Citation Summary
The data indicates a diverse range of studies involving C3, primarily focusing on its role in various biological contexts such as autoimmune diseases, renal inflammation, and complement activation. The use of C3 antibodies spans multiple species, including humans and mice, highlighting its significance in both clinical and experimental research settings.
Abcam Product Citation Table
Function
Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.
Complement C3b
Non-enzymatic component of C5 convertase (PubMed:28264884, PubMed:31507604, PubMed:3653927, PubMed:3897448). Generated following cleavage by C3 convertase, it covalently attaches to the surface of pathogens, where it acts as an opsonin that marks the surface of antigens for removal (PubMed:28264884, PubMed:31507604, PubMed:3653927, PubMed:3897448, PubMed:833545, PubMed:8349625). Complement C3b binds covalently via its reactive thioester, to cell surface carbohydrates or immune aggregates (PubMed:6903192). Together with complement C4b, it then recruits the serine protease complement C2b to form the C5 convertase, which cleaves and activate C5, the next component of the complement pathways (PubMed:12878586, PubMed:18204047, PubMed:2387864). In the alternative complement pathway, recruits the serine protease CFB to form the C5 convertase that cleaves and activates C5 (PubMed:624565, PubMed:6554279).
C3a anaphylatoxin
Mediator of local inflammatory process released following cleavage by C3 convertase (PubMed:6968751, PubMed:37169960, PubMed:37852260). Acts by binding to its receptor, C3AR1, activating G protein-coupled receptor signaling, promoting the phosphorylation, ARRB2-mediated internalization and endocytosis of C3AR1 (PubMed:8702752, PubMed:37169960, PubMed:37852260). C3a anaphylatoxin stimulates the activation of immune cells such as mast cells and basophilic leukocytes to release inflammation agents, such as cytokines, chemokines and histamine, which promote inflammation development (PubMed:23383423). Also acts as potent chemoattractant for the migration of macrophages and neutrophils to the inflamed tissues, resulting in neutralization of the inflammatory triggers by multiple ways, such as phagocytosis and generation of reactive oxidants (PubMed:23383423, PubMed:342601, PubMed:5778786).
Acylation stimulating protein
Adipogenic hormone that stimulates triglyceride synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial triglyceride clearance (PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750, PubMed:2909530, PubMed:8376604, PubMed:9059512). Appears to stimulate triglyceride synthesis via activation of the PLC, MAPK and AKT signaling pathways (PubMed:16333141). Acts by binding to its receptor, C5AR2, activating G protein-coupled receptor signaling, promoting the phosphorylation, ARRB2-mediated internalization and endocytosis of C5AR2 (PubMed:11773063, PubMed:12540846, PubMed:19615750). In contrast to C3a anaphylatoxin peptide, does not show pro-inflammatory activity (PubMed:37852260).
C3-beta-c
Acts as a chemoattractant for neutrophils in chronic inflammation.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
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.
Post-translational modifications
C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond (PubMed:7240134). During activation of the complement systems, the alpha chain is cleaved into C3a and C3b by the C3 convertase: C3b stays linked to the beta chain, while C3a is released in the plasma (PubMed:6611150, PubMed:6906228). The alpha chain is cleaved by the serine protease complement C2b component of the C3 convertase to generate C3a and C3b following activation by the classical, lectin and GZMK complement systems (PubMed:39914456, PubMed:39814882, PubMed:6611150, PubMed:6906228). The alpha chain is cleaved by CFB component of the C3 convertase to generate C3a and C3b following activation by the alternative complement system (PubMed:28264884, PubMed:31507604, PubMed:3638964, PubMed:6919543, PubMed:9748277).
C3a anaphylatoxin
C3a is further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP) (PubMed:4098172, PubMed:6968751). Levels of ASP are increased in adipocytes in the postprandial period and by insulin and dietary chylomicrons (PubMed:15833747).
Complement C3b
Complement C3b is rapidly split in two positions by factor I (CFI) and a cofactor (CFH) to form iC3b (inactivated C3b) and C3f which is released (PubMed:17320177, PubMed:28671664, PubMed:7360115). CFI and CFH catalyze proteolytic degradation of already-deposited complement C3b (PubMed:28671664). Then iC3b is slowly cleaved (possibly by CFI) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f (PubMed:16177781, PubMed:17051150, PubMed:17684013). Other proteases produce other fragments such as C3d or C3g (PubMed:7539791).
Complement C3b
Upon activation, the internal thioester bond reacts with carbohydrate antigens on the target surface to form amide or ester bonds, leading to covalent association with the surface of pathogens.
Complement C3b
Complement C3b interacts with complement C4b via a thioester linkage.
Phosphorylated by FAM20C in the extracellular medium.
(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.
(Microbial infection) Complement C3 beta chain is cleaved and inactivated by S.pyogenes SpeB.
(Microbial infection) Cleaved by N.meningitidis NalP between Leu-744 and Gly-745, generating a slightly shorter C3 alpha form and a slightly longer C3 beta form. The C3b-like fragment is degraded in the presence of the complement regulators CFH and CFI, preventing its deposition on the bacterial surface.
Tissue Specificity
Plasma.
Acylation stimulating protein
Produced in adipocytes and released into the plasma during both the fasting and postprandial periods.
Cellular localization
- Secreted
- Complement C3b
- Secreted
- Cell surface
- Covalently associated with the surface of pathogens: the internal thioester bond reacts with carbohydrate antigens on the target surface to form amide or ester bonds.
- C3a anaphylatoxin
- Secreted
Alternative names
CPAMD1, C3, Complement C3, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1