C3
entrez
718
canonical
uniprot
P01024
canonical
ensembl
ENSG00000125730
resolver
ensp
ENSP00000245907
resolver
enst
ENST00000245907
resolver
genesymbol
C3
resolver
genesymbol
HEL-S-62p
resolver
genesymbol_syn
CPAMD1
resolver
hgnc
HGNC:1318
resolver
uniprot
A7E236
resolver
uniprot
B4DR57
resolver
uniprot
V9HWA9
resolver
uniprot_entry
B4DR57_HUMAN
resolver
uniprot_entry
CO3_HUMAN
resolver
uniprot_entry
V9HWA9_HUMAN
resolver
uniprot_sec
A7E236
resolver
activity_regulation
ACTIVITY REGULATION: Complement activation is inhibited by VSIG4. {ECO:0000269|PubMed:17051150}.
uniprot
proteins
amino_acid_sequence
MGPTSGPSLLLLLLTHLPLALGSPMYSIITPNILRLESEETMVLEAHDAQGDVPVTVTVHDFPGKKLVLSSEKTVLTPATNHMGNVTFTIPANREFKSEKGRNKFVTVQATFGTQVVEKVVLVSLQSGYLFIQTDKTIYTPGSTVLYRIFTVNHKLLPVGRTVMVNIENPEGIPVKQDSLSSQNQLGVLPLSWDIPELVNMGQWKIRAYYENSPQQVFSTEFEVKEYVLPSFEVIVEPTEKFYYIYNEKGLEVTITARFLYGKKVEGTAFVIFGIQDGEQRISLPESLKRIPIEDGSGEVVLSRKVLLDGVQNPRAEDLVGKSLYVSATVILHSGSDMVQAERSGIPIVTSPYQIHFTKTPKYFKPGMPFDLMVFVTNPDGSPAYRVPVAVQGEDTVQSLTQGDGVAKLSINTHPSQKPLSITVRTKKQELSEAEQATRTMQALPYSTVGNSNNYLHLSVLRTELRPGETLNVNFLLRMDRAHEAKIRYYTYLIMNKGRLLKAGRQVREPGQDLVVLPLSITTDFIPSFRLVAYYTLIGASGQREVVADSVWVDVKDSCVGSLVVKSGQSEDRQPVPGQQMTLKIEGDHGARVVLVAVDKGVFVLNKKNKLTQSKIWDVVEKADIGCTPGSGKDYAGVFSDAGLTFTSSSGQQTAQRAELQCPQPAARRRRSVQLTEKRMDKVGKYPKELRKCCEDGMRENPMRFSCQRRTRFISLGEACKKVFLDCCNYITELRRQHARASHLGLARSNLDEDIIAEENIVSRSEFPESWLWNVEDLKEPPKNGISTKLMNIFLKDSITTWEILAVSMSDKKGICVADPFEVTVMQDFFIDLRLPYSVVRNEQVEIRAVLYNYRQNQELKVRVELLHNPAFCSLATTKRRHQQTVTIPPKSSLSVPYVIVPLKTGLQEVEVKAAVYHHFISDGVRKSLKVVPEGIRMNKTVAVRTLDPERLGREGVQKEDIPPADLSDQVPDTESETRILLQGTPVAQMTEDAVDAERLKHLIVTPSGCGEQNMIGMTPTVIAVHYLDETEQWEKFGLEKRQGALELIKKGYTQQLAFRQPSSAFAAFVKRAPSTWLTAYVVKVFSLAVNLIAIDSQVLCGAVKWLILEKQKPDGVFQEDAPVIHQEMIGGLRNNNEKDMALTAFVLISLQEAKDICEEQVNSLPGSITKAGDFLEANYMNLQRSYTVAIAGYALAQMGRLKGPLLNKFLTTAKDKNRWEDPGKQLYNVEATSYALLALLQLKDFDFVPPVVRWLNEQRYYGGGYGSTQATFMVFQALAQYQKDAPDHQELNLDVSLQLPSRSSKITHRIHWESASLLRSEETKENEGFTVTAEGKGQGTLSVVTMYHAKAKDQLTCNKFDLKVTIKPAPETEKRPQDAKNTMILEICTRYRGDQDATMSILDISMMTGFAPDTDDLKQLANGVDRYISKYELDKAFSDRNTLIIYLDKVSHSEDDCLAFKVHQYFNVELIQPGAVKVYAYYNLEESCTRFYHPEKEDGKLNKLCRDELCRCAEENCFIQKSDDKVTLEERLDKACEPGVDYVYKTRLVKVQLSNDFDEYIMAIEQTIKSGSDEVQVGQQRTFISPIKCREALKLEEKKHYLMWGLSSDFWGEKPNLSYIIGKDTWVEHWPEEDECQDEENQKQCQDLGAFTESMVVFGCPN
uniprot
proteins
disease_involvement
DISEASE: Complement component 3 deficiency (C3D) [MIM:613779]: 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. {ECO:0000269|PubMed:7961791}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 9 (ARMD9) [MIM:611378]: 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. {ECO:0000269|PubMed:17634448, ECO:0000269|PubMed:24036952}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Hemolytic uremic syndrome, atypical, 5 (AHUS5) [MIM:612925]: 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. {ECO:0000269|PubMed:18796626, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.; DISEASE: Note=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.
uniprot
proteins
function
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. {ECO:0000269|PubMed:12878586, ECO:0000269|PubMed:18204047, ECO:0000269|PubMed:28264884, ECO:0000269|PubMed:31507604, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:624565, ECO:0000269|PubMed:6554279}.; FUNCTION: [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). {ECO:0000269|PubMed:12878586, ECO:0000269|PubMed:18204047, ECO:0000269|PubMed:2387864, ECO:0000269|PubMed:28264884, ECO:0000269|PubMed:31507604, ECO:0000269|PubMed:3653927, ECO:0000269|PubMed:3897448, ECO:0000269|PubMed:624565, ECO:0000269|PubMed:6554279, ECO:0000269|PubMed:6903192, ECO:0000269|PubMed:833545, ECO:0000269|PubMed:8349625}.; FUNCTION: [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). {ECO:0000269|PubMed:342601, ECO:0000269|PubMed:37169960, ECO:0000269|PubMed:37852260, ECO:0000269|PubMed:5778786, ECO:0000269|PubMed:6968751, ECO:0000269|PubMed:8702752, ECO:0000303|PubMed:23383423}.; FUNCTION: [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). {ECO:0000269|PubMed:10432298, ECO:0000269|PubMed:11773063, ECO:0000269|PubMed:12540846, ECO:0000269|PubMed:15833747, ECO:0000269|PubMed:16333141, ECO:0000269|PubMed:19615750, ECO:0000269|PubMed:2909530, ECO:0000269|PubMed:37852260, ECO:0000269|PubMed:8376604, ECO:0000269|PubMed:9059512}.; FUNCTION: [C3-beta-c]: Acts as a chemoattractant for neutrophils in chronic inflammation. {ECO:0000250|UniProtKB:P01026}.
uniprot
proteins
mass_dalton
187148
uniprot
proteins
mutagenesis
MUTAGEN 404; /note="D->A: Decreased chemokine activity."; /evidence="ECO:0000269|PubMed:37169960"; MUTAGEN 1029; /note="D->A: Minor effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1030; /note="E->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1032; /note="E->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1035; /note="E->A: No effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651"; MUTAGEN 1042; /note="R->M: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651"; MUTAGEN 1108..1109; /note="IL->RR: Impaired binding of C3d to CR2; when associated with A-1163."; /evidence="ECO:0000269|PubMed:11387479"; MUTAGEN 1110; /note="E->A: No effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20951140"; MUTAGEN 1115; /note="D->A: No effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20951140"; MUTAGEN 1121; /note="D->A: No effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20951140"; MUTAGEN 1140; /note="D->A: No effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1153; /note="E->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1156; /note="D->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1159; /note="E->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1160; /note="E->A: Minor effect on binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1163; /note="N->A: No effect on binding of C3d to CR2. Impaired binding of C3d to CR2; when associated with 1108-R-R-1109."; /evidence="ECO:0000269|PubMed:11387479, ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1163; /note="N->R: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:11387479, ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"; MUTAGEN 1284; /note="K->A: Impaired binding of C3d to CR2."; /evidence="ECO:0000269|PubMed:20083651
uniprot
proteins
post_translational_modification
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). {ECO:0000269|PubMed:28264884, ECO:0000269|PubMed:31507604, ECO:0000269|PubMed:3638964, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:6611150, ECO:0000269|PubMed:6906228, ECO:0000269|PubMed:6919543, ECO:0000269|PubMed:7240134, ECO:0000269|PubMed:9748277}.; PTM: [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). {ECO:0000269|PubMed:15833747, ECO:0000269|PubMed:4098172, ECO:0000269|PubMed:6968751}.; PTM: [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). {ECO:0000269|PubMed:16177781, ECO:0000269|PubMed:17051150, ECO:0000269|PubMed:17320177, ECO:0000269|PubMed:17684013, ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:7360115, ECO:0000269|PubMed:7539791}.; PTM: [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. {ECO:0000269|PubMed:6903192}.; PTM: [Complement C3b]: Complement C3b interacts with complement C4b via a thioester linkage. {ECO:0000269|PubMed:1740458, ECO:0000269|PubMed:2387864}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}.; 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. {ECO:0000269|PubMed:21502375}.; PTM: (Microbial infection) Complement C3 beta chain is cleaved and inactivated by S.pyogenes SpeB. {ECO:0000269|PubMed:18160402}.; 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. {ECO:0000269|PubMed:24367091}.
uniprot
proteins
pubmed
10432298
uniprot
proteins
pubmed
11387479
uniprot
proteins
pubmed
11773063
uniprot
proteins
pubmed
1238393
uniprot
proteins
pubmed
12540846
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
12878586
uniprot
proteins
pubmed
14760718
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15713468
uniprot
proteins
pubmed
1577777
uniprot
proteins
pubmed
15809665
uniprot
proteins
pubmed
15833747
uniprot
proteins
pubmed
16177781
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16302015
uniprot
proteins
pubmed
16333141
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
17051150
uniprot
proteins
pubmed
17051160
uniprot
proteins
pubmed
17320177
uniprot
proteins
pubmed
17351618
uniprot
proteins
pubmed
1740458
uniprot
proteins
pubmed
17634448
uniprot
proteins
pubmed
17684013
uniprot
proteins
pubmed
18160402
uniprot
proteins
pubmed
18204047
uniprot
proteins
pubmed
18796626
uniprot
proteins
pubmed
18805911
uniprot
proteins
pubmed
19112495
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19503103
uniprot
proteins
pubmed
19615750
uniprot
proteins
pubmed
1976733
uniprot
proteins
pubmed
19913840
uniprot
proteins
pubmed
20083651
uniprot
proteins
pubmed
20513133
uniprot
proteins
pubmed
20951140
uniprot
proteins
pubmed
21055811
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21285368
uniprot
proteins
pubmed
21317894
uniprot
proteins
pubmed
21502375
uniprot
proteins
pubmed
21527715
uniprot
proteins
pubmed
21555552
uniprot
proteins
pubmed
22028381
uniprot
proteins
pubmed
23383423
uniprot
proteins
pubmed
2387864
uniprot
proteins
pubmed
24036952
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24367091
uniprot
proteins
pubmed
2473125
uniprot
proteins
pubmed
2579379
uniprot
proteins
pubmed
2584723
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
28264884
uniprot
proteins
pubmed
2849025
uniprot
proteins
pubmed
28671664
uniprot
proteins
pubmed
2909530
uniprot
proteins
pubmed
2972794
uniprot
proteins
pubmed
30643019
uniprot
proteins
pubmed
31507604
uniprot
proteins
pubmed
3260670
uniprot
proteins
pubmed
3279119
uniprot
proteins
pubmed
342601
uniprot
proteins
pubmed
3638964
uniprot
proteins
pubmed
3653927
uniprot
proteins
pubmed
37169960
uniprot
proteins
pubmed
37852260
uniprot
proteins
pubmed
3897448
uniprot
proteins
pubmed
39814882
uniprot
proteins
pubmed
39914456
uniprot
proteins
pubmed
4098172
uniprot
proteins
pubmed
5778786
uniprot
proteins
pubmed
6175959
uniprot
proteins
pubmed
624565
uniprot
proteins
pubmed
6554279
uniprot
proteins
pubmed
6611150
uniprot
proteins
pubmed
6903192
uniprot
proteins
pubmed
6906228
uniprot
proteins
pubmed
6919543
uniprot
proteins
pubmed
6968751
uniprot
proteins
pubmed
7240134
uniprot
proteins
pubmed
7360115
uniprot
proteins
pubmed
7539791
uniprot
proteins
pubmed
7961791
uniprot
proteins
pubmed
8175757
uniprot
proteins
pubmed
833545
uniprot
proteins
pubmed
8349625
uniprot
proteins
pubmed
8376604
uniprot
proteins
pubmed
8416818
uniprot
proteins
pubmed
8702752
uniprot
proteins
pubmed
9059512
uniprot
proteins
pubmed
9555951
uniprot
proteins
pubmed
9596584
uniprot
proteins
pubmed
9748277
uniprot
proteins
sequence_length
1663
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7240134}.; SUBCELLULAR LOCATION: [Complement C3b]: Secreted {ECO:0000269|PubMed:3653927, ECO:0000269|PubMed:3897448, ECO:0000269|PubMed:6903192, ECO:0000269|PubMed:833545, ECO:0000269|PubMed:8349625}. Cell surface {ECO:0000269|PubMed:3653927, ECO:0000269|PubMed:3897448, ECO:0000269|PubMed:6903192, ECO:0000269|PubMed:833545, ECO:0000269|PubMed:8349625}. Note=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. {ECO:0000269|PubMed:3653927, ECO:0000269|PubMed:3897448, ECO:0000269|PubMed:6903192, ECO:0000269|PubMed:833545, ECO:0000269|PubMed:8349625}.; SUBCELLULAR LOCATION: [C3a anaphylatoxin]: Secreted {ECO:0000269|PubMed:1238393}.
uniprot
proteins