UniProtKB - P12387 (CO3_CAVPO)
Complement C3
C3
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. 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 similarityActs as a chemoattractant for neutrophils in chronic inflammation.
By similaritySites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 1666 | Coordinates Mg2+ for interaction with Complement factor B Bb fragmentBy similarity | 1 |
GO - Molecular functioni
- C5L2 anaphylatoxin chemotactic receptor binding Source: UniProtKB
- endopeptidase inhibitor activity Source: InterPro
GO - Biological processi
- complement activation, alternative pathway Source: UniProtKB-KW
- complement activation, classical pathway Source: UniProtKB-KW
- inflammatory response Source: UniProtKB-KW
- positive regulation of glucose transmembrane transport Source: UniProtKB
- positive regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
- positive regulation of lipid storage Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- regulation of triglyceride biosynthetic process Source: UniProtKB
Keywordsi
Biological process | Complement alternate pathway, Complement pathway, Immunity, Inflammatory response, Innate immunity |
Protein family/group databases
MEROPSi | S01.236 |
Names & Taxonomyi
Protein namesi | Recommended name: Complement C3Cleaved into the following 11 chains: |
Gene namesi | Name:C3 |
Organismi | Cavia porcellus (Guinea pig) |
Taxonomic identifieri | 10141 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Hystricomorpha › Caviidae › Cavia |
Proteomesi |
|
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular space Source: InterPro
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | 2 PublicationsAdd BLAST | 22 | |
ChainiPRO_0000005901 | 23 – 1666 | Complement C3Add BLAST | 1644 | |
ChainiPRO_0000005902 | 23 – 671 | Complement C3 beta chainAdd BLAST | 649 | |
ChainiPRO_0000430429 | 567 – 665 | C3-beta-cBy similarityAdd BLAST | 99 | |
ChainiPRO_0000005903 | 676 – 1666 | Complement C3 alpha chainAdd BLAST | 991 | |
ChainiPRO_0000005904 | 676 – 753 | C3a anaphylatoxinAdd BLAST | 78 | |
ChainiPRO_0000005905 | 754 – 1666 | Complement C3b alpha' chainAdd BLAST | 913 | |
ChainiPRO_0000273943 | 754 – 964 | Complement C3c alpha' chain fragment 1By similarityAdd BLAST | 211 | |
ChainiPRO_0000273944 | 965 – 1308 | Complement C3dg fragmentBy similarityAdd BLAST | 344 | |
ChainiPRO_0000273945 | 965 – 1006 | Complement C3g fragmentBy similarityAdd BLAST | 42 | |
ChainiPRO_0000005906 | 1007 – 1308 | Complement C3d fragmentBy similarityAdd BLAST | 302 | |
PeptideiPRO_0000273946 | 1309 – 1325 | Complement C3f fragmentBy similarityAdd BLAST | 17 | |
ChainiPRO_0000273947 | 1326 – 1666 | Complement C3c alpha' chain fragment 2By similarityAdd BLAST | 341 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 70 | PhosphoserineBy similarity | 1 | |
Modified residuei | 296 | PhosphoserineBy similarity | 1 | |
Modified residuei | 302 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 557 ↔ 821 | Interchain (between beta and alpha chains)PROSITE-ProRule annotation | ||
Disulfide bondi | 630 ↔ 666 | By similarity | ||
Modified residuei | 676 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 698 ↔ 725 | By similarity | ||
Disulfide bondi | 699 ↔ 732 | By similarity | ||
Disulfide bondi | 712 ↔ 733 | By similarity | ||
Disulfide bondi | 878 ↔ 1517 | By similarity | ||
Glycosylationi | 944 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 973 | PhosphoserineBy similarity | 1 | |
Cross-linki | 1015 ↔ 1018 | Isoglutamyl cysteine thioester (Cys-Gln) | ||
Disulfide bondi | 1106 ↔ 1163 | By similarity | ||
Modified residuei | 1326 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 1363 ↔ 1493 | By similarity | ||
Disulfide bondi | 1394 ↔ 1462 | By similarity | ||
Disulfide bondi | 1510 ↔ 1515 | By similarity | ||
Disulfide bondi | 1522 ↔ 1593 | By similarity | ||
Disulfide bondi | 1540 ↔ 1664 | By similarity | ||
Modified residuei | 1576 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 1620 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1640 ↔ 1649 | By similarity |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 753 – 754 | Cleavage; by C3 convertase | 2 | |
Sitei | 964 – 965 | Cleavage; by factor IBy similarity | 2 | |
Sitei | 992 – 993 | Cleavage; by elastase | 2 | |
Sitei | 1308 – 1309 | Cleavage; by factor IBy similarity | 2 | |
Sitei | 1325 – 1326 | Cleavage; by factor IBy similarity | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Thioester bondProteomic databases
PRIDEi | P12387 |
Interactioni
Subunit structurei
C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2).
Interacts with VSIG4 (By similarity). 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) (By similarity). Forms the pro-C3-convertase enzyme complex by binding to Complement factor B Bb fragment (Bb), which is then stabilized by binding CFP, allowing the complex to become active (By similarity). The interaction with Bb is dependent on Mg2+ (By similarity). C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains). C3b interacts with CFH. C3d interacts with CFH. 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.
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 (By similarity).
By similarityGO - Molecular functioni
- C5L2 anaphylatoxin chemotactic receptor binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 10141.ENSCPOP00000003785 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 698 – 733 | Anaphylatoxin-likePROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 1522 – 1664 | NTRPROSITE-ProRule annotationAdd BLAST | 143 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1637 – 1662 | Interaction with CFP/properdinBy similarityAdd BLAST | 26 |
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG1366, Eukaryota |
InParanoidi | P12387 |
OMAi | KYMETGY |
OrthoDBi | 23785at2759 |
Family and domain databases
CDDi | cd00017, ANATO, 1 hit cd03583, NTR_complement_C3, 1 hit |
Gene3Di | 2.40.50.120, 1 hit 2.60.40.10, 2 hits 2.60.40.690, 1 hit |
InterProi | View protein in InterPro IPR009048, A-macroglobulin_rcpt-bd IPR036595, A-macroglobulin_rcpt-bd_sf IPR011625, A2M_N_BRD IPR011626, Alpha-macroglobulin_TED IPR000020, Anaphylatoxin/fibulin IPR018081, Anaphylatoxin_comp_syst IPR001840, Anaphylatoxn_comp_syst_dom IPR041425, C3/4/5_MG1 IPR035711, Complement_C3-like IPR013783, Ig-like_fold IPR001599, Macroglobln_a2 IPR019742, MacrogloblnA2_CS IPR002890, MG2 IPR041555, MG3 IPR040839, MG4 IPR001134, Netrin_domain IPR018933, Netrin_module_non-TIMP IPR035815, NTR_complement_C3 IPR008930, Terpenoid_cyclase/PrenylTrfase IPR008993, TIMP-like_OB-fold |
PANTHERi | PTHR11412:SF81, PTHR11412:SF81, 1 hit |
Pfami | View protein in Pfam PF00207, A2M, 1 hit PF07703, A2M_BRD, 1 hit PF07677, A2M_recep, 1 hit PF01821, ANATO, 1 hit PF17790, MG1, 1 hit PF01835, MG2, 1 hit PF17791, MG3, 1 hit PF17789, MG4, 1 hit PF01759, NTR, 1 hit PF07678, TED_complement, 1 hit |
PRINTSi | PR00004, ANAPHYLATOXN |
SMARTi | View 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 |
SUPFAMi | SSF47686, SSF47686, 1 hit SSF48239, SSF48239, 1 hit SSF49410, SSF49410, 1 hit SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS00477, ALPHA_2_MACROGLOBULIN, 1 hit PS01177, ANAPHYLATOXIN_1, 1 hit PS01178, ANAPHYLATOXIN_2, 1 hit PS50189, NTR, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MGPAAGPSLL LLLLASVSLA LGDPMYSIIT PNILRLENEE TVVLEAHEVQ
60 70 80 90 100
GDIPVTVTVH DFPAKKNVLS SEKTVLTSAT GYLGTVTIKI PASKEFKSDK
110 120 130 140 150
GRKLVVVQAA FGGTQLEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT
160 170 180 190 200
VDSDLLPVGR TIIVTIETPD GIPIKRDTLS SNNQHGILPL SWNIPELVNM
210 220 230 240 250
GQWKIQAFYE NSPKQVFSAE FEVKEYVLPS FEVLVEPTEK FYYIDDPKGL
260 270 280 290 300
EVNIIARFLY GKNVDGTAFV IFGVQDGDQR ISLAQSLTRV VIEDGSGEVV
310 320 330 340 350
LSRQVLLDGV QPSRPEALVG KSLYVSVTVI LHSGSDMVEA ERSGIPIVTS
360 370 380 390 400
PYQIHFTKTP KYFKPAMPFE IMVLVTNPDG SPAPHVPVVT QGSNVQSLTQ
410 420 430 440 450
ADGVARLSIN TPNTRQPLSV TVQTKKGGIP DARQAINTMQ ALPYTTMYNS
460 470 480 490 500
NNYLHLSMPR TELKPGETIN VNFHLRSDPN QEAKIRYYTY LIMNKGKLLK
510 520 530 540 550
VGRQPREPGQ ALVVLPMPIT KELIPSFRLV AYYTLIGASA QREVVADSVW
560 570 580 590 600
ADVRDSCVGT LVVKGGSGKD GQDKRQQHLP RQQMTLRIEG NQGARVGLVA
610 620 630 640 650
VDKGVFVLNK KHKLTQSKIW DVVEKADIGC TPGSGKDYAG VFTDAGLSFK
660 670 680 690 700
SSKAGLQTAQ REGLDCPKPA ARRRRSVQLM ERRMDKAGKY KSKELRRCCE
710 720 730 740 750
DGMRENPMQF SCQRRARYVS LGEACVKAFL DCCTYMAQLR QQHRREQNLG
760 770 780 790 800
LARSDMDEDI IPEEDIISRS QFPESWLWTI EELKEPERNG ISTKTMNIFL
810 820 830 840 850
KDSITTWEIL AVSLSDKKGI CVADPFEVTV MQDFFIDLRL PYSVVRNEQV
860 870 880 890 900
EIRAVLYNYR EAQSLKVRVE LLHNPAFCSL ATAKKRHTQT VTIGPKSSVA
910 920 930 940 950
VPYVLVPLKI GLQEVEVKAA VYNYFISDGV KKTLKVVPEG MRVNKTVAIR
960 970 980 990 1000
TLNPEQLGQG GVQREEIPAA DLSDQVPDTD SETKILLQGT PVAQMAEDAV
1010 1020 1030 1040 1050
DAERLKHLII TPSGCGEQNM IGMTPTVIAV HYLDQTEQWE KFGLEKRQEA
1060 1070 1080 1090 1100
LNLINRGYTQ QLAFKQPNWA YAAFKNRASS TWLTAYVVKV FSLAANLIGI
1110 1120 1130 1140 1150
DSEVLCGAVK WLILEKQKPD GVFQEDGPVI HQEMIGGVRT AQEADVSLTA
1160 1170 1180 1190 1200
FVLIALQEAK DICRAQVNNL EANINKAGDY IESRYADVRR PYTLAIAGYA
1210 1220 1230 1240 1250
LALLERLNGA TLQKFLNAAT EKNRWEEARQ KLYSVEATSY ALLALLLLKD
1260 1270 1280 1290 1300
FDAVPPVVRW LNEQRYYGRG YGSTQATFMV FQALAQYQTD VPDHKDLNME
1310 1320 1330 1340 1350
VALQLPSRSS PSKFRLVWEA GSLLRSEATK QNEGFKLTAK GKGQGTLSVV
1360 1370 1380 1390 1400
AVYYAKTKRK VVCKNFDLRV TLKPAPDTVK KPQEAKSTMI LGICTRYLGD
1410 1420 1430 1440 1450
QDATMSILDI SMMTGFIPDT DDLKLLATGV DRYISKYEMN KDFSKNTLII
1460 1470 1480 1490 1500
YLDKVSHSEE ECLSFKIHQF FNVGLIQPGS VKVYSYYNLD ETCTQFYHPE
1510 1520 1530 1540 1550
KEDGMLNKLC HKDLCRCAEE NCFIQLPEKI TLDERLEKAC EPGVDYVYKT
1560 1570 1580 1590 1600
KLLKMELSDD FDEYIMTIEQ VIKSGSDEVQ AGKERRFISH IKCRDALHLK
1610 1620 1630 1640 1650
EGKHYLMWGL SSDLWGERPN MSYIIGKDTW VEAWPEAEEC QDEENQQQCQ
1660
DLGTFTENMV VFGCPN
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 731 | D → N AA sequence (PubMed:3064079).Curated | 1 | |
Sequence conflicti | 1018 | Q → E AA sequence (PubMed:6838833).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M34054 mRNA Translation: AAA37038.1 |
PIRi | A37156, C3GP |
RefSeqi | NP_001166374.1, NM_001172903.1 |
Genome annotation databases
GeneIDi | 100135462 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M34054 mRNA Translation: AAA37038.1 |
PIRi | A37156, C3GP |
RefSeqi | NP_001166374.1, NM_001172903.1 |
3D structure databases
SMRi | P12387 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10141.ENSCPOP00000003785 |
Protein family/group databases
MEROPSi | S01.236 |
Proteomic databases
PRIDEi | P12387 |
Protocols and materials databases
ABCDi | P12387, 6 sequenced antibodies |
Genome annotation databases
GeneIDi | 100135462 |
Organism-specific databases
CTDi | 718 |
Phylogenomic databases
eggNOGi | KOG1366, Eukaryota |
InParanoidi | P12387 |
OMAi | KYMETGY |
OrthoDBi | 23785at2759 |
Family and domain databases
CDDi | cd00017, ANATO, 1 hit cd03583, NTR_complement_C3, 1 hit |
Gene3Di | 2.40.50.120, 1 hit 2.60.40.10, 2 hits 2.60.40.690, 1 hit |
InterProi | View protein in InterPro IPR009048, A-macroglobulin_rcpt-bd IPR036595, A-macroglobulin_rcpt-bd_sf IPR011625, A2M_N_BRD IPR011626, Alpha-macroglobulin_TED IPR000020, Anaphylatoxin/fibulin IPR018081, Anaphylatoxin_comp_syst IPR001840, Anaphylatoxn_comp_syst_dom IPR041425, C3/4/5_MG1 IPR035711, Complement_C3-like IPR013783, Ig-like_fold IPR001599, Macroglobln_a2 IPR019742, MacrogloblnA2_CS IPR002890, MG2 IPR041555, MG3 IPR040839, MG4 IPR001134, Netrin_domain IPR018933, Netrin_module_non-TIMP IPR035815, NTR_complement_C3 IPR008930, Terpenoid_cyclase/PrenylTrfase IPR008993, TIMP-like_OB-fold |
PANTHERi | PTHR11412:SF81, PTHR11412:SF81, 1 hit |
Pfami | View protein in Pfam PF00207, A2M, 1 hit PF07703, A2M_BRD, 1 hit PF07677, A2M_recep, 1 hit PF01821, ANATO, 1 hit PF17790, MG1, 1 hit PF01835, MG2, 1 hit PF17791, MG3, 1 hit PF17789, MG4, 1 hit PF01759, NTR, 1 hit PF07678, TED_complement, 1 hit |
PRINTSi | PR00004, ANAPHYLATOXN |
SMARTi | View 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 |
SUPFAMi | SSF47686, SSF47686, 1 hit SSF48239, SSF48239, 1 hit SSF49410, SSF49410, 1 hit SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS00477, ALPHA_2_MACROGLOBULIN, 1 hit PS01177, ANAPHYLATOXIN_1, 1 hit PS01178, ANAPHYLATOXIN_2, 1 hit PS50189, NTR, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CO3_CAVPO | |
Accessioni | P12387Primary (citable) accession number: P12387 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1989 |
Last sequence update: | June 1, 1994 | |
Last modified: | June 2, 2021 | |
This is version 142 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |