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Protein

Complement C3

Gene

C3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity
C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.By similarity
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).7 Publications

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).2 Publications
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).2 Publications

GO - Molecular functioni

  • C5L2 anaphylatoxin chemotactic receptor binding Source: UniProtKB
  • endopeptidase inhibitor activity Source: InterPro
  • serine-type endopeptidase activity Source: Reactome
  • signaling receptor binding Source: ProtInc

GO - Biological processi

Keywordsi

Biological processComplement alternate pathway, Complement pathway, Fatty acid metabolism, Immunity, Inflammatory response, Innate immunity, Lipid metabolism

Enzyme and pathway databases

BRENDAi3.4.21.47 2681
ReactomeiR-HSA-173736 Alternative complement activation
R-HSA-174577 Activation of C3 and C5
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-418594 G alpha (i) signalling events
R-HSA-6798695 Neutrophil degranulation
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-977606 Regulation of Complement cascade
SABIO-RKiP01024
SIGNORiP01024

Protein family/group databases

MEROPSiI39.950

Names & Taxonomyi

Protein namesi
Recommended name:
Complement C3
Alternative name(s):
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1
Cleaved into the following 12 chains:
Gene namesi
Name:C3
Synonyms:CPAMD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000125730.16
HGNCiHGNC:1318 C3
MIMi120700 gene
neXtProtiNX_P01024

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Complement component 3 deficiency (C3D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613779
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001985549D → N in C3D; impairs secretion; variant confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs1449441916Ensembl.1
Macular degeneration, age-related, 9 (ARMD9)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:611378
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070941155K → Q in ARMD9; results in resistance to proteolytic inactivation by CFH and CFI. 1 PublicationCorresponds to variant dbSNP:rs147859257EnsemblClinVar.1
Hemolytic uremic syndrome atypical 5 (AHUS5)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
Disease descriptionAn 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.
See also OMIM:612925
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063213592R → Q in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909583EnsemblClinVar.1
Natural variantiVAR_063214592R → W in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs771353792Ensembl.1
Natural variantiVAR_063654603F → V in AHUS5. 1 Publication1
Natural variantiVAR_063215735R → W in AHUS5. 1 PublicationCorresponds to variant dbSNP:rs117793540EnsemblClinVar.1
Natural variantiVAR_0636551042R → L in AHUS5. 1 Publication1
Natural variantiVAR_0632161094A → V in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909584EnsemblClinVar.1
Natural variantiVAR_0632171115D → N in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909585EnsemblClinVar.1
Natural variantiVAR_0632181158C → W in AHUS5. 1 Publication1
Natural variantiVAR_0632191161Q → K in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication1
Natural variantiVAR_0632201464H → D in AHUS5. 1 Publication1
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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1029D → A: Minor effect on binding of C3d to CR2. 2 Publications1
Mutagenesisi1030E → A: Impaired binding of C3d to CR2. 2 Publications1
Mutagenesisi1032E → A: Impaired binding of C3d to CR2. 2 Publications1
Mutagenesisi1035E → A: No effect on binding of C3d to CR2. 1 Publication1
Mutagenesisi1042R → M: Impaired binding of C3d to CR2. 1 Publication1
Mutagenesisi1108 – 1109IL → RR: Impaired binding of C3d to CR2; when associated with A-1163. 1 Publication2
Mutagenesisi1110E → A: No effect on binding of C3d to CR2. 1 Publication1
Mutagenesisi1115D → A: No effect on binding of C3d to CR2. 1 Publication1
Mutagenesisi1121D → A: No effect on binding of C3d to CR2. 1 Publication1
Mutagenesisi1140D → A: No effect on binding of C3d to CR2. 2 Publications1
Mutagenesisi1153E → A: Impaired binding of C3d to CR2. 2 Publications1
Mutagenesisi1156D → A: Impaired binding of C3d to CR2. 2 Publications1
Mutagenesisi1159E → A: Impaired binding of C3d to CR2. 2 Publications1
Mutagenesisi1160E → A: Minor effect on binding of C3d to CR2. 2 Publications1
Mutagenesisi1163N → A: No effect on binding of C3d to CR2. Impaired binding of C3d to CR2; when associated with 1108-R-R-1109. 3 Publications1
Mutagenesisi1163N → R: Impaired binding of C3d to CR2. 3 Publications1
Mutagenesisi1284K → A: Impaired binding of C3d to CR2. 1 Publication1

Keywords - Diseasei

Age-related macular degeneration, Disease mutation, Hemolytic uremic syndrome

Organism-specific databases

DisGeNETi718
GeneReviewsiC3
MalaCardsiC3
MIMi611378 phenotype
612925 phenotype
613779 phenotype
OpenTargetsiENSG00000125730
Orphaneti93575 Atypical hemolytic-uremic syndrome with C3 anomaly
280133 Complement component 3 deficiency
279 NON RARE IN EUROPE: Age-related macular degeneration
PharmGKBiPA25897

Chemistry databases

ChEMBLiCHEMBL4917
DrugBankiDB00028 Immune Globulin Human
DB01915 S-Hydroxycysteine

Polymorphism and mutation databases

BioMutaiC3
DMDMi119370332

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000000590723 – 1663Complement C3Add BLAST1641
ChainiPRO_000000590823 – 667Complement C3 beta chainAdd BLAST645
ChainiPRO_0000430430569 – 667C3-beta-cBy similarityAdd BLAST99
ChainiPRO_0000005909672 – 1663Complement C3 alpha chainAdd BLAST992
ChainiPRO_0000005910672 – 748C3a anaphylatoxinAdd BLAST77
ChainiPRO_0000419935672 – 747Acylation stimulating proteinAdd BLAST76
ChainiPRO_0000005911749 – 1663Complement C3b alpha' chainAdd BLAST915
ChainiPRO_0000005912749 – 954Complement C3c alpha' chain fragment 1Add BLAST206
ChainiPRO_0000005913955 – 1303Complement C3dg fragmentAdd BLAST349
ChainiPRO_0000005914955 – 1001Complement C3g fragmentAdd BLAST47
ChainiPRO_00000059151002 – 1303Complement C3d fragmentAdd BLAST302
PeptideiPRO_00000059161304 – 1320Complement C3f fragment1 PublicationAdd BLAST17
ChainiPRO_00002739481321 – 1663Complement C3c alpha' chain fragment 2Add BLAST343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38Phosphoserine; by FAM20C1 Publication1
Modified residuei70Phosphoserine; by FAM20C1 Publication1
Glycosylationi85N-linked (GlcNAc...) asparagine7 Publications1
Modified residuei297Phosphoserine; by FAM20C1 Publication1
Modified residuei303Phosphoserine; by FAM20C1 Publication1
Disulfide bondi559 ↔ 816Interchain (between beta and alpha chains)
Disulfide bondi627 ↔ 662
Modified residuei672Phosphoserine; by FAM20C1 Publication1
Disulfide bondi693 ↔ 7201 Publication
Disulfide bondi694 ↔ 727
Disulfide bondi707 ↔ 728
Disulfide bondi873 ↔ 1513
Glycosylationi939N-linked (GlcNAc...) asparagine3 Publications1
Modified residuei968Phosphoserine; by FAM20C1 Publication1
Cross-linki1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)
Disulfide bondi1101 ↔ 1158
Modified residuei1321Phosphoserine; by FAM20C1 Publication1
Disulfide bondi1358 ↔ 1489
Disulfide bondi1389 ↔ 1458
Disulfide bondi1506 ↔ 1511
Disulfide bondi1518 ↔ 1590
Disulfide bondi1537 ↔ 1661
Modified residuei1573Phosphoserine; by FAM20C1 Publication1
Glycosylationi1617N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1637 ↔ 1646

Post-translational modificationi

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.
Phosphorylated by FAM20C in the extracellular medium.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei747 – 748Cleavage; by carboxypeptidases2
Sitei748 – 749Cleavage; by C3 convertase2
Sitei954 – 955Cleavage; by factor ISequence analysis2
Sitei1303 – 1304Cleavage; by factor I2
Sitei1320 – 1321Cleavage; by factor I2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Thioester bond

Proteomic databases

EPDiP01024
PaxDbiP01024
PeptideAtlasiP01024
PRIDEiP01024
ProteomicsDBi51308

2D gel databases

DOSAC-COBS-2DPAGEiP01024
SWISS-2DPAGEiP01024

PTM databases

CarbonylDBiP01024
GlyConnecti110
iPTMnetiP01024
PhosphoSitePlusiP01024
UniCarbKBiP01024

Miscellaneous databases

PMAP-CutDBiP01024

Expressioni

Tissue specificityi

Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods.2 Publications

Gene expression databases

BgeeiENSG00000125730 Expressed in 228 organ(s), highest expression level in parietal pleura
CleanExiHS_C3
ExpressionAtlasiP01024 baseline and differential
GenevisibleiP01024 HS

Organism-specific databases

HPAiCAB004209
HPA003563
HPA020432

Interactioni

Subunit structurei

C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond. C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4. 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. Interacts with S.aureus immunoglobulin-binding protein sbi, this prevents interaction between C3dg and CR2. Interacts with S.aureus fib. Interacts (both C3a and ASP) with C5AR2; the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis of GRP77.12 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107179, 30 interactors
ComplexPortaliCPX-973 Complement C3b complex
CORUMiP01024
DIPiDIP-35180N
IntActiP01024, 22 interactors
MINTiP01024
STRINGi9606.ENSP00000245907

Chemistry databases

BindingDBiP01024

Structurei

Secondary structure

11663
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP01024
SMRiP01024
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01024

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini693 – 728Anaphylatoxin-likePROSITE-ProRule annotationAdd BLAST36
Domaini1518 – 1661NTRPROSITE-ProRule annotationAdd BLAST144

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1424 – 1456Properdin-bindingAdd BLAST33

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOGENOMiHOG000286028
HOVERGENiHBG005110
InParanoidiP01024
KOiK03990
OMAiQDGEQRI
OrthoDBiEOG091G00FJ
PhylomeDBiP01024
TreeFamiTF313285

Family and domain databases

CDDicd00017 ANATO, 1 hit
cd03583 NTR_complement_C3, 1 hit
Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR000020 Anaphylatoxin/fibulin
IPR018081 Anaphylatoxin_comp_syst
IPR001840 Anaphylatoxn_comp_syst_dom
IPR035711 Complement_C3-like
IPR013783 Ig-like_fold
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR035815 NTR_complement_C3
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11412:SF81 PTHR11412:SF81, 1 hit
PfamiView protein in Pfam
PF00207 A2M, 1 hit
PF07678 A2M_comp, 1 hit
PF01835 A2M_N, 1 hit
PF07703 A2M_N_2, 1 hit
PF07677 A2M_recep, 1 hit
PF01821 ANATO, 1 hit
PF01759 NTR, 1 hit
PF10569 Thiol-ester_cl, 1 hit
PRINTSiPR00004 ANAPHYLATOXN
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SM00104 ANATO, 1 hit
SM00643 C345C, 1 hit
SUPFAMiSSF47686 SSF47686, 1 hit
SSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
PS01177 ANAPHYLATOXIN_1, 1 hit
PS01178 ANAPHYLATOXIN_2, 1 hit
PS50189 NTR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P01024-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGPTSGPSLL LLLLTHLPLA LGSPMYSIIT PNILRLESEE TMVLEAHDAQ
60 70 80 90 100
GDVPVTVTVH DFPGKKLVLS SEKTVLTPAT NHMGNVTFTI PANREFKSEK
110 120 130 140 150
GRNKFVTVQA TFGTQVVEKV VLVSLQSGYL FIQTDKTIYT PGSTVLYRIF
160 170 180 190 200
TVNHKLLPVG RTVMVNIENP EGIPVKQDSL SSQNQLGVLP LSWDIPELVN
210 220 230 240 250
MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE KFYYIYNEKG
260 270 280 290 300
LEVTITARFL YGKKVEGTAF VIFGIQDGEQ RISLPESLKR IPIEDGSGEV
310 320 330 340 350
VLSRKVLLDG VQNPRAEDLV GKSLYVSATV ILHSGSDMVQ AERSGIPIVT
360 370 380 390 400
SPYQIHFTKT PKYFKPGMPF DLMVFVTNPD GSPAYRVPVA VQGEDTVQSL
410 420 430 440 450
TQGDGVAKLS INTHPSQKPL SITVRTKKQE LSEAEQATRT MQALPYSTVG
460 470 480 490 500
NSNNYLHLSV LRTELRPGET LNVNFLLRMD RAHEAKIRYY TYLIMNKGRL
510 520 530 540 550
LKAGRQVREP GQDLVVLPLS ITTDFIPSFR LVAYYTLIGA SGQREVVADS
560 570 580 590 600
VWVDVKDSCV GSLVVKSGQS EDRQPVPGQQ MTLKIEGDHG ARVVLVAVDK
610 620 630 640 650
GVFVLNKKNK LTQSKIWDVV EKADIGCTPG SGKDYAGVFS DAGLTFTSSS
660 670 680 690 700
GQQTAQRAEL QCPQPAARRR RSVQLTEKRM DKVGKYPKEL RKCCEDGMRE
710 720 730 740 750
NPMRFSCQRR TRFISLGEAC KKVFLDCCNY ITELRRQHAR ASHLGLARSN
760 770 780 790 800
LDEDIIAEEN IVSRSEFPES WLWNVEDLKE PPKNGISTKL MNIFLKDSIT
810 820 830 840 850
TWEILAVSMS DKKGICVADP FEVTVMQDFF IDLRLPYSVV RNEQVEIRAV
860 870 880 890 900
LYNYRQNQEL KVRVELLHNP AFCSLATTKR RHQQTVTIPP KSSLSVPYVI
910 920 930 940 950
VPLKTGLQEV EVKAAVYHHF ISDGVRKSLK VVPEGIRMNK TVAVRTLDPE
960 970 980 990 1000
RLGREGVQKE DIPPADLSDQ VPDTESETRI LLQGTPVAQM TEDAVDAERL
1010 1020 1030 1040 1050
KHLIVTPSGC GEQNMIGMTP TVIAVHYLDE TEQWEKFGLE KRQGALELIK
1060 1070 1080 1090 1100
KGYTQQLAFR QPSSAFAAFV KRAPSTWLTA YVVKVFSLAV NLIAIDSQVL
1110 1120 1130 1140 1150
CGAVKWLILE KQKPDGVFQE DAPVIHQEMI GGLRNNNEKD MALTAFVLIS
1160 1170 1180 1190 1200
LQEAKDICEE QVNSLPGSIT KAGDFLEANY MNLQRSYTVA IAGYALAQMG
1210 1220 1230 1240 1250
RLKGPLLNKF LTTAKDKNRW EDPGKQLYNV EATSYALLAL LQLKDFDFVP
1260 1270 1280 1290 1300
PVVRWLNEQR YYGGGYGSTQ ATFMVFQALA QYQKDAPDHQ ELNLDVSLQL
1310 1320 1330 1340 1350
PSRSSKITHR IHWESASLLR SEETKENEGF TVTAEGKGQG TLSVVTMYHA
1360 1370 1380 1390 1400
KAKDQLTCNK FDLKVTIKPA PETEKRPQDA KNTMILEICT RYRGDQDATM
1410 1420 1430 1440 1450
SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD RNTLIIYLDK
1460 1470 1480 1490 1500
VSHSEDDCLA FKVHQYFNVE LIQPGAVKVY AYYNLEESCT RFYHPEKEDG
1510 1520 1530 1540 1550
KLNKLCRDEL CRCAEENCFI QKSDDKVTLE ERLDKACEPG VDYVYKTRLV
1560 1570 1580 1590 1600
KVQLSNDFDE YIMAIEQTIK SGSDEVQVGQ QRTFISPIKC REALKLEEKK
1610 1620 1630 1640 1650
HYLMWGLSSD FWGEKPNLSY IIGKDTWVEH WPEEDECQDE ENQKQCQDLG
1660
AFTESMVVFG CPN
Length:1,663
Mass (Da):187,148
Last modified:December 12, 2006 - v2
Checksum:i30C2832A9E75FFC4
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QXZ3M0QXZ3_HUMAN
Complement C3
C3
100Annotation score:
M0QYC8M0QYC8_HUMAN
Complement C3
C3
192Annotation score:
M0R0Q9M0R0Q9_HUMAN
Complement C3
C3
101Annotation score:
M0R1Q1M0R1Q1_HUMAN
Complement C3
C3
103Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti681D → N AA sequence (PubMed:1238393).Curated1
Sequence conflicti700E → Q AA sequence (PubMed:1238393).Curated1
Sequence conflicti1026H → S AA sequence (PubMed:6175959).Curated1

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001983102R → G in allele C3F; associated with susceptibility to ARMD9; results in decreased binding affinity for regulator factor H; results in reduced sensitivity to cleavage by factor I. 3 PublicationsCorresponds to variant dbSNP:rs2230199EnsemblClinVar.1
Natural variantiVAR_070941155K → Q in ARMD9; results in resistance to proteolytic inactivation by CFH and CFI. 1 PublicationCorresponds to variant dbSNP:rs147859257EnsemblClinVar.1
Natural variantiVAR_001984314P → L3 PublicationsCorresponds to variant dbSNP:rs1047286EnsemblClinVar.1
Natural variantiVAR_020262469E → D. Corresponds to variant dbSNP:rs11569422EnsemblClinVar.1
Natural variantiVAR_001985549D → N in C3D; impairs secretion; variant confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs1449441916Ensembl.1
Natural variantiVAR_063213592R → Q in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909583EnsemblClinVar.1
Natural variantiVAR_063214592R → W in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs771353792Ensembl.1
Natural variantiVAR_063654603F → V in AHUS5. 1 Publication1
Natural variantiVAR_063215735R → W in AHUS5. 1 PublicationCorresponds to variant dbSNP:rs117793540EnsemblClinVar.1
Natural variantiVAR_019206863R → K1 PublicationCorresponds to variant dbSNP:rs11569472Ensembl.1
Natural variantiVAR_0636551042R → L in AHUS5. 1 Publication1
Natural variantiVAR_0632161094A → V in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909584EnsemblClinVar.1
Natural variantiVAR_0632171115D → N in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 PublicationCorresponds to variant dbSNP:rs121909585EnsemblClinVar.1
Natural variantiVAR_0632181158C → W in AHUS5. 1 Publication1
Natural variantiVAR_0632191161Q → K in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication1
Natural variantiVAR_0192071224G → D1 PublicationCorresponds to variant dbSNP:rs11569534EnsemblClinVar.1
Natural variantiVAR_0192081367I → T1 PublicationCorresponds to variant dbSNP:rs11569541Ensembl.1
Natural variantiVAR_0632201464H → D in AHUS5. 1 Publication1
Natural variantiVAR_0297921521Q → R. Corresponds to variant dbSNP:rs7256789Ensembl.1
Natural variantiVAR_0297931601H → N. Corresponds to variant dbSNP:rs1803225Ensembl.1
Natural variantiVAR_0293261619S → R. Corresponds to variant dbSNP:rs2230210EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02765 mRNA Translation: AAA85332.1
AY513239 Genomic DNA Translation: AAR89906.1
CH471139 Genomic DNA Translation: EAW69071.1
BC150179 mRNA Translation: AAI50180.1
BC150200 mRNA Translation: AAI50201.1
CCDSiCCDS32883.1
PIRiA94065 C3HU
RefSeqiNP_000055.2, NM_000064.3
UniGeneiHs.529053

Genome annotation databases

EnsembliENST00000245907; ENSP00000245907; ENSG00000125730
GeneIDi718
KEGGihsa:718

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

C3base

C3 mutation db

Wikipedia

Complement C3 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02765 mRNA Translation: AAA85332.1
AY513239 Genomic DNA Translation: AAR89906.1
CH471139 Genomic DNA Translation: EAW69071.1
BC150179 mRNA Translation: AAI50180.1
BC150200 mRNA Translation: AAI50201.1
CCDSiCCDS32883.1
PIRiA94065 C3HU
RefSeqiNP_000055.2, NM_000064.3
UniGeneiHs.529053

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C3DX-ray1.80A996-1287[»]
1GHQX-ray2.04A996-1300[»]
1W2SX-ray-A996-1299[»]
2A73X-ray3.30A23-665[»]
B673-1663[»]
2A74X-ray2.40A/D23-665[»]
B/E749-936[»]
C/F1321-1663[»]
2GOXX-ray2.20A/C996-1287[»]
2I07X-ray4.00A23-667[»]
B749-1663[»]
2ICEX-ray3.10A/D23-664[»]
B/E749-954[»]
C/F1321-1663[»]
2ICFX-ray4.10A23-664[»]
B749-1663[»]
2NOJX-ray2.70A/C/E/G996-1287[»]
2QKIX-ray2.40A/D23-665[»]
B/E749-936[»]
C/F1321-1663[»]
2WIIX-ray2.70A23-667[»]
B749-1663[»]
2WINX-ray3.90A/C/E/G23-667[»]
B/D/F/H749-1663[»]
2WY7X-ray1.70A996-1303[»]
2WY8X-ray1.70A996-1303[»]
2XQWX-ray2.31A/B996-1287[»]
2XWBX-ray3.49A/C23-664[»]
B/D752-1663[»]
2XWJX-ray4.00A/C/E/G23-667[»]
B/D/F/H749-1663[»]
3D5RX-ray2.10A/B996-1287[»]
3D5SX-ray2.30A/B996-1287[»]
3G6JX-ray3.10A/C23-666[»]
B/D749-1663[»]
3L3OX-ray3.40A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
3L5NX-ray7.54A23-667[»]
B749-1663[»]
3NMSX-ray4.10A23-667[»]
B749-954[»]
C1321-1663[»]
3OEDX-ray3.16A/B996-1303[»]
3OHXX-ray3.50A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
3OXUX-ray2.10A/B/C996-1303[»]
3RJ3X-ray2.35A/B/C996-1303[»]
3T4AX-ray3.40A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
4HW5X-ray2.25A/B672-748[»]
4HWJX-ray2.60A672-747[»]
4I6OX-ray2.14A672-748[»]
4M76X-ray2.80A994-1288[»]
4ONTX-ray2.15A/B/C996-1303[»]
4ZH1X-ray2.24A/B/C996-1303[»]
5FO7X-ray2.80A23-667[»]
B749-1663[»]
5FO8X-ray2.40A23-667[»]
B749-1663[»]
5FO9X-ray3.30A/D23-667[»]
B/E749-1663[»]
5FOAX-ray4.19A/C23-667[»]
B/D749-1663[»]
5FOBX-ray2.60A23-667[»]
B749-1663[»]
5M6WX-ray6.00A/G23-667[»]
B/H751-1663[»]
5NBQX-ray3.18A/B/C994-1287[»]
5O32X-ray4.21A/E23-667[»]
B/F749-1663[»]
5O35X-ray4.20A23-667[»]
B749-1663[»]
6EHGX-ray2.65A23-665[»]
B749-1663[»]
ProteinModelPortaliP01024
SMRiP01024
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107179, 30 interactors
ComplexPortaliCPX-973 Complement C3b complex
CORUMiP01024
DIPiDIP-35180N
IntActiP01024, 22 interactors
MINTiP01024
STRINGi9606.ENSP00000245907

Chemistry databases

BindingDBiP01024
ChEMBLiCHEMBL4917
DrugBankiDB00028 Immune Globulin Human
DB01915 S-Hydroxycysteine

Protein family/group databases

MEROPSiI39.950

PTM databases

CarbonylDBiP01024
GlyConnecti110
iPTMnetiP01024
PhosphoSitePlusiP01024
UniCarbKBiP01024

Polymorphism and mutation databases

BioMutaiC3
DMDMi119370332

2D gel databases

DOSAC-COBS-2DPAGEiP01024
SWISS-2DPAGEiP01024

Proteomic databases

EPDiP01024
PaxDbiP01024
PeptideAtlasiP01024
PRIDEiP01024
ProteomicsDBi51308

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245907; ENSP00000245907; ENSG00000125730
GeneIDi718
KEGGihsa:718

Organism-specific databases

CTDi718
DisGeNETi718
EuPathDBiHostDB:ENSG00000125730.16
GeneCardsiC3
GeneReviewsiC3
H-InvDBiHIX0020036
HGNCiHGNC:1318 C3
HPAiCAB004209
HPA003563
HPA020432
MalaCardsiC3
MIMi120700 gene
611378 phenotype
612925 phenotype
613779 phenotype
neXtProtiNX_P01024
OpenTargetsiENSG00000125730
Orphaneti93575 Atypical hemolytic-uremic syndrome with C3 anomaly
280133 Complement component 3 deficiency
279 NON RARE IN EUROPE: Age-related macular degeneration
PharmGKBiPA25897
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOGENOMiHOG000286028
HOVERGENiHBG005110
InParanoidiP01024
KOiK03990
OMAiQDGEQRI
OrthoDBiEOG091G00FJ
PhylomeDBiP01024
TreeFamiTF313285

Enzyme and pathway databases

BRENDAi3.4.21.47 2681
ReactomeiR-HSA-173736 Alternative complement activation
R-HSA-174577 Activation of C3 and C5
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-418594 G alpha (i) signalling events
R-HSA-6798695 Neutrophil degranulation
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-977606 Regulation of Complement cascade
SABIO-RKiP01024
SIGNORiP01024

Miscellaneous databases

ChiTaRSiC3 human
EvolutionaryTraceiP01024
GeneWikiiComplement_component_3
GenomeRNAii718
PMAP-CutDBiP01024
PROiPR:P01024
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125730 Expressed in 228 organ(s), highest expression level in parietal pleura
CleanExiHS_C3
ExpressionAtlasiP01024 baseline and differential
GenevisibleiP01024 HS

Family and domain databases

CDDicd00017 ANATO, 1 hit
cd03583 NTR_complement_C3, 1 hit
Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR000020 Anaphylatoxin/fibulin
IPR018081 Anaphylatoxin_comp_syst
IPR001840 Anaphylatoxn_comp_syst_dom
IPR035711 Complement_C3-like
IPR013783 Ig-like_fold
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR035815 NTR_complement_C3
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11412:SF81 PTHR11412:SF81, 1 hit
PfamiView protein in Pfam
PF00207 A2M, 1 hit
PF07678 A2M_comp, 1 hit
PF01835 A2M_N, 1 hit
PF07703 A2M_N_2, 1 hit
PF07677 A2M_recep, 1 hit
PF01821 ANATO, 1 hit
PF01759 NTR, 1 hit
PF10569 Thiol-ester_cl, 1 hit
PRINTSiPR00004 ANAPHYLATOXN
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SM00104 ANATO, 1 hit
SM00643 C345C, 1 hit
SUPFAMiSSF47686 SSF47686, 1 hit
SSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
PS01177 ANAPHYLATOXIN_1, 1 hit
PS01178 ANAPHYLATOXIN_2, 1 hit
PS50189 NTR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCO3_HUMAN
AccessioniPrimary (citable) accession number: P01024
Secondary accession number(s): A7E236
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 12, 2006
Last modified: November 7, 2018
This is version 231 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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