CO3_CAVPO
ID CO3_CAVPO Reviewed; 1666 AA.
AC P12387;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Complement C3;
DE Contains:
DE RecName: Full=Complement C3 beta chain;
DE Contains:
DE RecName: Full=C3-beta-c;
DE Short=C3bc;
DE Contains:
DE RecName: Full=Complement C3 alpha chain;
DE Contains:
DE RecName: Full=C3a anaphylatoxin;
DE Contains:
DE RecName: Full=Complement C3b alpha' chain;
DE Contains:
DE RecName: Full=Complement C3c alpha' chain fragment 1;
DE Contains:
DE RecName: Full=Complement C3dg fragment;
DE Contains:
DE RecName: Full=Complement C3g fragment;
DE Contains:
DE RecName: Full=Complement C3d fragment;
DE Contains:
DE RecName: Full=Complement C3f fragment;
DE Contains:
DE RecName: Full=Complement C3c alpha' chain fragment 2;
DE Flags: Precursor;
GN Name=C3;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hartley; TISSUE=Liver;
RX PubMed=1973176; DOI=10.1172/jci114721;
RA Auerbach H.S., Burger R., Dodds A., Colten H.R.;
RT "Molecular basis of complement C3 deficiency in guinea pigs.";
RL J. Clin. Invest. 86:96-106(1990).
RN [2]
RP PROTEIN SEQUENCE OF 23-38.
RC TISSUE=Macrophage;
RX PubMed=6458605; DOI=10.1016/s0021-9258(18)42933-x;
RA Goldberger G., Thomas M.L., Tack B.F., Williams J., Colten H.R.,
RA Abraham G.N.;
RT "NH2-terminal structure and cleavage of guinea pig pro-C3, the precursor of
RT the third complement component.";
RL J. Biol. Chem. 256:12617-12619(1981).
RN [3]
RP PROTEIN SEQUENCE OF 23-38; 676-687 AND 993-1032, AND THIOESTER BOND.
RC TISSUE=Plasma;
RX PubMed=6838833; DOI=10.1021/bi00273a036;
RA Thomas M.L., Tack B.F.;
RT "Identification and alignment of a thiol ester site in the third component
RT of guinea pig complement.";
RL Biochemistry 22:942-947(1983).
RN [4]
RP PROTEIN SEQUENCE OF 676-753.
RX PubMed=3064079;
RA Gerard N.P., Lively M.O., Gerard C.;
RT "Amino acid sequence of guinea pig C3a anaphylatoxin.";
RL Protein Seq. Data Anal. 1:473-478(1988).
CC -!- FUNCTION: C3 plays a central role in the activation of the complement
CC system. Its processing by C3 convertase is the central reaction in both
CC classical and alternative complement pathways. After activation C3b can
CC bind covalently, via its reactive thioester, to cell surface
CC carbohydrates or immune aggregates.
CC -!- FUNCTION: Derived from proteolytic degradation of complement C3, C3a
CC anaphylatoxin is a mediator of local inflammatory process. It induces
CC the contraction of smooth muscle, increases vascular permeability and
CC causes histamine release from mast cells and basophilic leukocytes. In
CC chronic inflammation, acts as a chemoattractant for neutrophils (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: [C3-beta-c]: Acts as a chemoattractant for neutrophils in
CC chronic inflammation. {ECO:0000250}.
CC -!- SUBUNIT: C3dg interacts with CR2 (via the N-terminal Sushi domains 1
CC and 2). Interacts with VSIG4 (By similarity). C3 precursor is first
CC processed by the removal of 4 Arg residues, forming two chains, beta
CC and alpha, linked by a disulfide bond. C3 convertase activates C3 by
CC cleaving the alpha chain, releasing C3a anaphylatoxin and generating
CC C3b (beta chain + alpha' chain) (By similarity). Forms the pro-C3-
CC convertase enzyme complex by binding to Complement factor B Bb fragment
CC (Bb), which is then stabilized by binding CFP, allowing the complex to
CC become active (By similarity). The interaction with Bb is dependent on
CC Mg2+ (By similarity). C3b interacts with CR1 (via Sushi 8 and Sushi 9
CC domains). C3b interacts with CFH. C3d interacts with CFH. C3dg
CC interacts with CR2 (via the N-terminal Sushi domains 1 and 2). During
CC pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer)
CC with AGT and the proform of PRG2. Interacts with VSIG4. Interacts with
CC S.aureus immunoglobulin-binding protein sbi, this prevents interaction
CC between C3dg and CR2. Interacts with S.aureus fib. Interacts (both C3a
CC and ASP) with C5AR2; the interaction occurs with higher affinity for
CC ASP, enhancing the phosphorylation and activation of C5AR2, recruitment
CC of ARRB2 to the cell surface and endocytosis of GRP77 (By similarity).
CC {ECO:0000250|UniProtKB:P01024}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: C3b is rapidly split in two positions by factor I and a cofactor
CC to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is
CC slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha'
CC chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other
CC proteases produce other fragments such as C3d or C3g (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P01024}.
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DR EMBL; M34054; AAA37038.1; -; mRNA.
DR PIR; A37156; C3GP.
DR RefSeq; NP_001166374.1; NM_001172903.1.
DR AlphaFoldDB; P12387; -.
DR SMR; P12387; -.
DR STRING; 10141.ENSCPOP00000003785; -.
DR MEROPS; I39.950; -.
DR MEROPS; S01.236; -.
DR PRIDE; P12387; -.
DR ABCD; P12387; 6 sequenced antibodies.
DR GeneID; 100135462; -.
DR KEGG; cpoc:100135462; -.
DR CTD; 718; -.
DR eggNOG; KOG1366; Eukaryota.
DR InParanoid; P12387; -.
DR OrthoDB; 23785at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0031715; F:C5L2 anaphylatoxin chemotactic receptor binding; ISS:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; ISS:UniProtKB.
DR GO; GO:0010884; P:positive regulation of lipid storage; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010866; P:regulation of triglyceride biosynthetic process; ISS:UniProtKB.
DR CDD; cd00017; ANATO; 1.
DR CDD; cd03583; NTR_complement_C3; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011625; A2M_N_BRD.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR000020; Anaphylatoxin/fibulin.
DR InterPro; IPR018081; Anaphylatoxin_comp_syst.
DR InterPro; IPR001840; Anaphylatoxn_comp_syst_dom.
DR InterPro; IPR041425; C3/4/5_MG1.
DR InterPro; IPR035711; Complement_C3-like.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001599; Macroglobln_a2.
DR InterPro; IPR019742; MacrogloblnA2_CS.
DR InterPro; IPR002890; MG2.
DR InterPro; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR035815; NTR_complement_C3.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11412:SF81; PTHR11412:SF81; 1.
DR Pfam; PF00207; A2M; 1.
DR Pfam; PF07703; A2M_BRD; 1.
DR Pfam; PF07677; A2M_recep; 1.
DR Pfam; PF01821; ANATO; 1.
DR Pfam; PF17790; MG1; 1.
DR Pfam; PF01835; MG2; 1.
DR Pfam; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 1.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF07678; TED_complement; 1.
DR PRINTS; PR00004; ANAPHYLATOXN.
DR SMART; SM01360; A2M; 1.
DR SMART; SM01359; A2M_N_2; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SMART; SM00104; ANATO; 1.
DR SMART; SM00643; C345C; 1.
DR SUPFAM; SSF47686; SSF47686; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR PROSITE; PS01177; ANAPHYLATOXIN_1; 1.
DR PROSITE; PS01178; ANAPHYLATOXIN_2; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Complement alternate pathway;
KW Complement pathway; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW Phosphoprotein; Reference proteome; Secreted; Signal; Thioester bond.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:6458605,
FT ECO:0000269|PubMed:6838833"
FT CHAIN 23..1666
FT /note="Complement C3"
FT /id="PRO_0000005901"
FT CHAIN 23..671
FT /note="Complement C3 beta chain"
FT /id="PRO_0000005902"
FT CHAIN 567..665
FT /note="C3-beta-c"
FT /evidence="ECO:0000250"
FT /id="PRO_0000430429"
FT CHAIN 676..1666
FT /note="Complement C3 alpha chain"
FT /id="PRO_0000005903"
FT CHAIN 676..753
FT /note="C3a anaphylatoxin"
FT /id="PRO_0000005904"
FT CHAIN 754..1666
FT /note="Complement C3b alpha' chain"
FT /id="PRO_0000005905"
FT CHAIN 754..964
FT /note="Complement C3c alpha' chain fragment 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000273943"
FT CHAIN 965..1308
FT /note="Complement C3dg fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000273944"
FT CHAIN 965..1006
FT /note="Complement C3g fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000273945"
FT CHAIN 1007..1308
FT /note="Complement C3d fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005906"
FT PEPTIDE 1309..1325
FT /note="Complement C3f fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000273946"
FT CHAIN 1326..1666
FT /note="Complement C3c alpha' chain fragment 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000273947"
FT DOMAIN 698..733
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1522..1664
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 1637..1662
FT /note="Interaction with CFP/properdin"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT SITE 753..754
FT /note="Cleavage; by C3 convertase"
FT SITE 964..965
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000250"
FT SITE 992..993
FT /note="Cleavage; by elastase"
FT SITE 1308..1309
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000250"
FT SITE 1325..1326
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000250"
FT SITE 1666
FT /note="Coordinates Mg2+ for interaction with Complement
FT factor B Bb fragment"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 676
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 973
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 1326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 1576
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT CARBOHYD 944
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1620
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 557..821
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 630..666
FT /evidence="ECO:0000250"
FT DISULFID 698..725
FT /evidence="ECO:0000250"
FT DISULFID 699..732
FT /evidence="ECO:0000250"
FT DISULFID 712..733
FT /evidence="ECO:0000250"
FT DISULFID 878..1517
FT /evidence="ECO:0000250"
FT DISULFID 1106..1163
FT /evidence="ECO:0000250"
FT DISULFID 1363..1493
FT /evidence="ECO:0000250"
FT DISULFID 1394..1462
FT /evidence="ECO:0000250"
FT DISULFID 1510..1515
FT /evidence="ECO:0000250"
FT DISULFID 1522..1593
FT /evidence="ECO:0000250"
FT DISULFID 1540..1664
FT /evidence="ECO:0000250"
FT DISULFID 1640..1649
FT /evidence="ECO:0000250"
FT CROSSLNK 1015..1018
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT CONFLICT 731
FT /note="D -> N (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1018
FT /note="Q -> E (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1666 AA; 186488 MW; 1C1F1219944AFD49 CRC64;
MGPAAGPSLL LLLLASVSLA LGDPMYSIIT PNILRLENEE TVVLEAHEVQ GDIPVTVTVH
DFPAKKNVLS SEKTVLTSAT GYLGTVTIKI PASKEFKSDK GRKLVVVQAA FGGTQLEKVV
LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VDSDLLPVGR TIIVTIETPD GIPIKRDTLS
SNNQHGILPL SWNIPELVNM GQWKIQAFYE NSPKQVFSAE FEVKEYVLPS FEVLVEPTEK
FYYIDDPKGL EVNIIARFLY GKNVDGTAFV IFGVQDGDQR ISLAQSLTRV VIEDGSGEVV
LSRQVLLDGV QPSRPEALVG KSLYVSVTVI LHSGSDMVEA ERSGIPIVTS PYQIHFTKTP
KYFKPAMPFE IMVLVTNPDG SPAPHVPVVT QGSNVQSLTQ ADGVARLSIN TPNTRQPLSV
TVQTKKGGIP DARQAINTMQ ALPYTTMYNS NNYLHLSMPR TELKPGETIN VNFHLRSDPN
QEAKIRYYTY LIMNKGKLLK VGRQPREPGQ ALVVLPMPIT KELIPSFRLV AYYTLIGASA
QREVVADSVW ADVRDSCVGT LVVKGGSGKD GQDKRQQHLP RQQMTLRIEG NQGARVGLVA
VDKGVFVLNK KHKLTQSKIW DVVEKADIGC TPGSGKDYAG VFTDAGLSFK SSKAGLQTAQ
REGLDCPKPA ARRRRSVQLM ERRMDKAGKY KSKELRRCCE DGMRENPMQF SCQRRARYVS
LGEACVKAFL DCCTYMAQLR QQHRREQNLG LARSDMDEDI IPEEDIISRS QFPESWLWTI
EELKEPERNG ISTKTMNIFL KDSITTWEIL AVSLSDKKGI CVADPFEVTV MQDFFIDLRL
PYSVVRNEQV EIRAVLYNYR EAQSLKVRVE LLHNPAFCSL ATAKKRHTQT VTIGPKSSVA
VPYVLVPLKI GLQEVEVKAA VYNYFISDGV KKTLKVVPEG MRVNKTVAIR TLNPEQLGQG
GVQREEIPAA DLSDQVPDTD SETKILLQGT PVAQMAEDAV DAERLKHLII TPSGCGEQNM
IGMTPTVIAV HYLDQTEQWE KFGLEKRQEA LNLINRGYTQ QLAFKQPNWA YAAFKNRASS
TWLTAYVVKV FSLAANLIGI DSEVLCGAVK WLILEKQKPD GVFQEDGPVI HQEMIGGVRT
AQEADVSLTA FVLIALQEAK DICRAQVNNL EANINKAGDY IESRYADVRR PYTLAIAGYA
LALLERLNGA TLQKFLNAAT EKNRWEEARQ KLYSVEATSY ALLALLLLKD FDAVPPVVRW
LNEQRYYGRG YGSTQATFMV FQALAQYQTD VPDHKDLNME VALQLPSRSS PSKFRLVWEA
GSLLRSEATK QNEGFKLTAK GKGQGTLSVV AVYYAKTKRK VVCKNFDLRV TLKPAPDTVK
KPQEAKSTMI LGICTRYLGD QDATMSILDI SMMTGFIPDT DDLKLLATGV DRYISKYEMN
KDFSKNTLII YLDKVSHSEE ECLSFKIHQF FNVGLIQPGS VKVYSYYNLD ETCTQFYHPE
KEDGMLNKLC HKDLCRCAEE NCFIQLPEKI TLDERLEKAC EPGVDYVYKT KLLKMELSDD
FDEYIMTIEQ VIKSGSDEVQ AGKERRFISH IKCRDALHLK EGKHYLMWGL SSDLWGERPN
MSYIIGKDTW VEAWPEAEEC QDEENQQQCQ DLGTFTENMV VFGCPN
