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Protein

Complement C3

Gene

C3

Organism
Sus scrofa (Pig)
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 (By similarity).By similarity
Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity).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 post-prandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-internalization and recycling of C5AR2 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Protein family/group databases

MEROPSiI39.950

Names & Taxonomyi

Protein namesi
Gene namesi
Name:C3
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000041992223 – 1661Complement C3Add BLAST1639
ChainiPRO_000041992323 – 665Complement C3 beta chainBy similarityAdd BLAST643
ChainiPRO_0000430432567 – 665C3-beta-cBy similarityAdd BLAST99
ChainiPRO_0000419924670 – 1661Complement C3 alpha chainBy similarityAdd BLAST992
ChainiPRO_0000419925670 – 746C3a anaphylatoxinAdd BLAST77
ChainiPRO_0000419926670 – 745Acylation stimulating proteinBy similarityAdd BLAST76
ChainiPRO_0000419927747 – 1661Complement C3b alpha' chainBy similarityAdd BLAST915
ChainiPRO_0000419928747 – 953Complement C3c alpha' chain fragment 1By similarityAdd BLAST207
ChainiPRO_0000419929954 – 1302Complement C3dg fragmentBy similarityAdd BLAST349
ChainiPRO_0000419930954 – 1000Complement C3g fragmentBy similarityAdd BLAST47
ChainiPRO_00004199311001 – 1302Complement C3d fragmentBy similarityAdd BLAST302
PeptideiPRO_00004199321303 – 1319Complement C3f fragmentBy similarityAdd BLAST17
ChainiPRO_00004199331320 – 1661Complement C3c alpha' chain fragment 2By similarityAdd BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38PhosphoserineBy similarity1
Modified residuei70PhosphoserineBy similarity1
Modified residuei302PhosphoserineBy similarity1
Disulfide bondi557 ↔ 814Interchain (between beta and alpha chains)PROSITE-ProRule annotation
Disulfide bondi625 ↔ 660By similarity
Modified residuei670PhosphoserineBy similarity1
Disulfide bondi691 ↔ 718By similarity
Disulfide bondi692 ↔ 725By similarity
Disulfide bondi705 ↔ 726By similarity
Disulfide bondi871 ↔ 1511By similarity
Glycosylationi937N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei966PhosphoserineBy similarity1
Cross-linki1008 ↔ 1011Isoglutamyl cysteine thioester (Cys-Gln)By similarity
Disulfide bondi1099 ↔ 1156By similarity
Modified residuei1319PhosphoserineBy similarity1
Disulfide bondi1356 ↔ 1487By similarity
Disulfide bondi1387 ↔ 1456By similarity
Disulfide bondi1504 ↔ 1509By similarity
Disulfide bondi1516 ↔ 1588By similarity
Disulfide bondi1535 ↔ 1659By similarity
Modified residuei1571PhosphoserineBy similarity1
Glycosylationi1615N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1635 ↔ 1644By similarity

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 carboxylases to release the C-termianl 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 (By similarity).By similarity
Phosphorylated by FAM20C in the extracellular medium.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei745 – 746Cleavage; by carboxypeptidasesBy similarity2
Sitei746 – 747Cleavage; by C3 convertaseBy similarity2
Sitei1301 – 1302Cleavage; by factor IBy similarity2
Sitei1318 – 1319Cleavage; by factor IBy similarity2

Keywords - PTMi

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

Proteomic databases

PaxDbiP01025
PeptideAtlasiP01025
PRIDEiP01025

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). Interacts with VSIG4. 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
gCC7EYC82EBI-11688674,EBI-11688666From Suid alphaherpesvirus 1.

GO - Molecular functioni

Protein-protein interaction databases

IntActiP01025, 1 interactor
STRINGi9823.ENSSSCP00000014399

Structurei

3D structure databases

ProteinModelPortaliP01025
SMRiP01025
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini691 – 726Anaphylatoxin-likePROSITE-ProRule annotationAdd BLAST36
Domaini1516 – 1659NTRPROSITE-ProRule annotationAdd BLAST144

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1422 – 1454Properdin-bindingBy similarityAdd BLAST33

Keywords - Domaini

Signal

Phylogenomic databases

InParanoidiP01025
KOiK03990

Family and domain databases

CDDicd03583 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

Sequencei

Sequence statusi: Complete.

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

P01025-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSTSGPRLL LLLLTSLPLA LGDPIYTIIT PNVLRLESEE MVVLEAHEGQ
60 70 80 90 100
GDIRVSVTVH DFPAKRQVLS SETTTLNNAN NYLSTVNIKI PASKEFKSEK
110 120 130 140 150
GHKFVTVQAL FGNVQVEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT
160 170 180 190 200
VDHKLLPVGQ TIVVTIETPE GIDIKRDSLS SHNQFGILAL SWNIPELVNM
210 220 230 240 250
GQWKIRAHYE DAPQQVFSAE FEVKEYVLPS FEVQVEPSEK FYYIDDPNGL
260 270 280 290 300
TVNIIARFLY GESVDGTAFV IFGVQDGDQR ISLSQSLTRV PIIDGTGEAT
310 320 330 340 350
LSQGVLLNGV HYSSVNDLVG KSIYVSVTVI LNSGSDMVEA ERTGIPIVTS
360 370 380 390 400
PYQIHFTKTP KFFKPAMPFD LMVYVTNPDG SPARHIPVVT EDFKVRSLTQ
410 420 430 440 450
EDGVAKLSIN TPDNRNSLPI TVRTEKDGIP AARQASKTMH VLPYNTQGNS
460 470 480 490 500
KNYLHLSLPR VELKPGENLN VNFHLRTDPG YQDKIRYFTY LIMNKGKLLK
510 520 530 540 550
VGRQPRESGQ VVVVLPLTIT TDFIPSFRLV AYYTLIAANG QREVVADSVW
560 570 580 590 600
VDVKDSCVGT LVVKGGGKQD KQHRPGQQMT LEIQGERGAR VGLVAVDKGV
610 620 630 640 650
FVLNKKNKLT QRRIWDVVEK ADIGCTPGSG KDFAGVFTDA GLAFKSSKGL
660 670 680 690 700
QTPQRADLEC PKPAARKRRS VQLMEKRMDK LGQYSKDVRR CCEHGMRDNP
710 720 730 740 750
MKFSCQRRAQ FIQHGDACVK AFLDCCEYIA KLRQQHSRNK PLGLARSDLD
760 770 780 790 800
EEIIPEEDII SRSQFPESWL WTIEEFKEPD KNGISTKTMN VFLKDSITTW
810 820 830 840 850
EILAVSLSDK KGICVADPYE VVVKQDFFID LRLPYSVVRN EQVEIRAILY
860 870 880 890 900
NYREAEDLKV RVELLYNPAF CSLATAKKRH QQTLTVPAKS SVPVPYIIVP
910 920 930 940 950
LKTGLQEVEV KAAVYNHFIS DGVKKTLKVV PEGMRVNKTV VTRTLDPEHK
960 970 980 990 1000
GQQGVQREEI PPADLSDQVP DTESETKILL QGTPVAQMVE DAIDGDRLKH
1010 1020 1030 1040 1050
LIQTPSGCGE QNMIGMTPTV IAVHYLDSTE QWEKFGLEKR QEALELIKKG
1060 1070 1080 1090 1100
YTQQLAFRQK NSAFAAFQDR LSSTLLTAYV VKVFAMAANL IAIDSQVLCG
1110 1120 1130 1140 1150
AVKWLILEKQ KPDGVFEENG PVIHQEMIGG FKNTEEKDVS LTAFVLIALQ
1160 1170 1180 1190 1200
EAKDICEPQV NSLLRSINKA RDFLADYYLE LKRPYTVAIA GYALALSDKL
1210 1220 1230 1240 1250
DEPFLNKLLS TAKERNRWEE PGQKLHNVEA TSYALLALLV VKDFDSVPPI
1260 1270 1280 1290 1300
VRWLNEQRYY GGGYGSTQAT FMVFQALAQY QKDVPDHKDL NLDVSIHLPS
1310 1320 1330 1340 1350
RSAPVRHRIL WESASLLRSE ETKENEGFTL IAEGKGQGTL SVVTMYHGKA
1360 1370 1380 1390 1400
KGKTTCKKFD LKVSIHPAPE PVKKPQEAKS SMVLDICTRY LGNQDATMSI
1410 1420 1430 1440 1450
LDISMMTGFS PDTEDLKLLS TGVDRYISKY ELNKALSNKN TLIIYLDKIS
1460 1470 1480 1490 1500
HTLEDCISFK VHQYFNVGLI QPGSVKVYSY YNLDESCTRF YHPEKEDGML
1510 1520 1530 1540 1550
NKLCHKEMCR CAEENCFMHH DEEEVTLDDR LERACEPGVD YVYKTRLLKK
1560 1570 1580 1590 1600
ELSDDFDDYI MVIEQIIKSG SDEVQVGQER RFISHIKCRE ALKLKEGGHY
1610 1620 1630 1640 1650
LVWGVSSDLW GEKPNISYII GKDTWVELWP DGDVCQDEEN QKQCQDLANF
1660
SENMVVFGCP N
Length:1,661
Mass (Da):186,807
Last modified:October 31, 2012 - v2
Checksum:i4899D0914BE3310C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti679D → N AA sequence (PubMed:956663).Curated1
Sequence conflicti687 – 688DV → EL AA sequence (PubMed:956663).Curated2
Sequence conflicti698D → N AA sequence (PubMed:956663).Curated1
Sequence conflicti713 – 716QHGD → HQGN AA sequence (PubMed:956663).Curated4
Sequence conflicti724D → N AA sequence (PubMed:956663).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF154933 mRNA Translation: AAG40565.1
AJ494748 Genomic DNA Translation: CAD38823.2
AF110278 mRNA Translation: AAC99785.1
PIRiA01259
RefSeqiNP_999174.1, NM_214009.1
UniGeneiSsc.61

Genome annotation databases

GeneIDi397072
KEGGissc:397072

Similar proteinsi

Entry informationi

Entry nameiCO3_PIG
AccessioniPrimary (citable) accession number: P01025
Secondary accession number(s): O97940, Q9GKP1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 31, 2012
Last modified: April 25, 2018
This is version 99 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health