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Details on Person UniProt:P01024 C3
| Class:Id | ReferenceGeneProduct:52470 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Sat February 7 2015;chain:23-1663 added on Sat February 7 2015;chain:23-667 added on Sat February 7 2015;chain:569-667 added on Sat February 7 2015;chain:672-1663 added on Sat February 7 2015;chain:672-748 added on Sat February 7 2015;chain:672-747 added on Sat February 7 2015;chain:749-1663 added on Sat February 7 2015;chain:749-954 added on Sat February 7 2015;chain:955-1303 added on Sat February 7 2015;chain:955-1001 added on Sat February 7 2015;chain:1002-1303 added on Sat February 7 2015;peptide:1304-1320 added on Sat February 7 2015;chain:1321-1663 added on Sat February 7 2015 |
| _displayName | UniProt:P01024 C3 |
| _timestamp | 2026-02-20 22:53:19 |
| chain | signal peptide:1-22 chain:23-1663 chain:23-667 chain:569-667 chain:672-1663 chain:672-748 chain:672-747 chain:749-1663 chain:749-954 chain:955-1303 chain:955-1001 chain:1002-1303 peptide:1304-1320 chain:1321-1663 |
| checksum | 30C2832A9E75FFC4 |
| comment | 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.FUNCTION 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).FUNCTION 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).FUNCTION 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).FUNCTION Acts as a chemoattractant for neutrophils in chronic inflammation.ACTIVITY REGULATION Complement activation is inhibited by VSIG4.SUBUNIT In absence of complement activation, the C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond.SUBUNIT Complement C3b is composed of complement C3b and complement C3 beta chains that are associated via disulfide bonds (PubMed:28671664). Non-enzymatic component of the C5 convertase, also named C4bC2bC3b, composed of the serine protease complement C2b (C2), complement C3b, as well as complement C4b (C4) (PubMed:12878586, PubMed:17051150, PubMed:1740458, PubMed:18204047, PubMed:2387864). Non-enzymatic component of the C5 convertase of the alternative complement pathways composed of the serine protease complement CFB and complement C3b (PubMed:30643019, PubMed:3638964, PubMed:624565, PubMed:6554279, PubMed:6919543, PubMed:9748277). Interacts with CFP; interaction takes place together with CFB in the alternative complement system and allows the complex to become active (PubMed:28264884, PubMed:31507604). Interacts with CR1 (via Sushi 8 and Sushi 9 domains) (PubMed:2972794, PubMed:8175757). Interacts with CFH (PubMed:21285368).SUBUNIT Interacts with CFH (PubMed:21285368, PubMed:21317894). Interacts with CR2 (PubMed:20951140).SUBUNIT During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2 (PubMed:7539791). Interacts with CR2 (via the N-terminal Sushi domains 1 and 2) (PubMed:11387479, PubMed:20083651, PubMed:21527715).SUBUNIT (Microbial infection) C3b interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 2 (HHV-2) envelope glycoprotein C; this interaction inhibits the activation of the complement system.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus immunoglobulin-binding protein Sbi; this interaction prevents the association between C3dg and CR2.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein Fib.INTERACTION 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.SUBCELLULAR LOCATION Plasma.TISSUE SPECIFICITY Produced in adipocytes and released into the plasma during both the fasting and postprandial periods.PTM 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).PTM 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).PTM 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).PTM 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.PTM Complement C3b interacts with complement C4b via a thioester linkage.PTM Phosphorylated by FAM20C in the extracellular medium.PTM (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.PTM (Microbial infection) Complement C3 beta chain is cleaved and inactivated by S.pyogenes SpeB.PTM (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.POLYMORPHISM There are two alleles: C3S (C3 slow), the most common allele in all races and C3F (C3 fast), relatively frequent in Caucasians, less common in Black Americans, extremely rare in Orientals.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.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.CAUTION An article reported the interaction surface between C3 and CR2 (PubMed:11387479). According to a another paper, it is however an artifact and can be ascribed to the presence of zinc acetate in the buffer (PubMed:21527715).CAUTION The difference between allele C3S (C3 slow) and allele C3F (C3 fast) was reported to be caused by a an Asn at position 1216 instead of an Asp (PubMed:2473125). The paper was however retracted (PubMed:2584723).ONLINE INFORMATION C3 mutation dbONLINE INFORMATION Complement C3 entry |
| description | recommendedName: fullName evidence="91"Complement C3 alternativeName: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1 component recommendedName: Complement C3 beta chain /component component recommendedName: C3-beta-c shortName: C3bc /component component recommendedName: Complement C3 alpha chain /component component recommendedName: fullName evidence="88"C3a anaphylatoxin /component component recommendedName: fullName evidence="92"Acylation stimulating protein shortName evidence="93"ASP alternativeName: fullName evidence="89"C3adesArg /component component recommendedName: Complement C3b alternativeName: Complement C3b-alpha' chain /component component recommendedName: Complement C3c alpha' chain fragment 1 /component component recommendedName: Complement C3dg fragment /component component recommendedName: Complement C3g fragment /component component recommendedName: Complement C3d fragment /component component recommendedName: Complement C3f fragment /component component recommendedName: Complement C3c alpha' chain fragment 2 /component |
| geneName | C3 CPAMD1 |
| identifier | P01024 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Age-related macular degeneration Cleavage on pair of basic residues Complement alternate pathway Complement pathway Direct protein sequencing Disease variant Disulfide bond Fatty acid metabolism Glycoprotein Hemolytic uremic syndrome Immunity Inflammatory response Innate immunity Lipid metabolism Phosphoprotein Proteomics identification Reference proteome Secreted Signal Thioester bond |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | C3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8958493] ENSEMBL:ENSG00000125730 C3 [Homo sapiens] |
| secondaryIdentifier | CO3_HUMAN A7E236 |
| sequenceLength | 1663 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:166820] C3 alpha chain [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:166821] C3 beta chain [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:166828] C3a [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:166830] C3b alpha' [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:182452] dNQ-C3(672-1663) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:198999] C3d fragment [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:976779] C3f [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:976816] C3c alpha' chain fragment 1 precursor [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:976818] C3c alpha' chain fragment 2 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:977593] C3 beta chain [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2530413] deamidated L-glutamine at 1013 [IntraChainCrosslinkedResidue:2530417] Intra-chain Crosslink via S-(L-isoglutamyl)-L-cysteine at 1010 and 1013 [ModifiedResidue:8957034] phosphorylated residue at unknown position |
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No pathways have been reviewed or authored by UniProt:P01024 C3 (52470)
