CO3_PIG
ID CO3_PIG Reviewed; 1661 AA.
AC P01025; O97940; Q9GKP1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 25-MAY-2022, entry version 117.
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=Acylation stimulating protein;
DE Short=ASP;
DE AltName: Full=C3adesArg;
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=11419349; DOI=10.1046/j.1365-2052.2001.0647f.x;
RA Wimmers K., Mekchay S., Ponsuksili S., Hardge T., Yerle M., Schellander K.;
RT "Polymorphic sites in exon 15 and 30 of the porcine C3 gene.";
RL Anim. Genet. 32:46-47(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=12927082; DOI=10.1186/1297-9686-35-s1-s83;
RA Mekchay S., Ponsuksili S., Schellander K., Wimmers K.;
RT "Association of the porcine C3 gene with haemolytic complement activity in
RT the pig.";
RL Genet. Sel. Evol. 35:S83-S96(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=12557058; DOI=10.1007/s00251-002-0524-y;
RA Wimmers K., Mekchay S., Schellander K., Ponsuksili S.;
RT "Molecular characterization of the pig C3 gene and its association with
RT complement activity.";
RL Immunogenetics 54:714-724(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 607-799.
RC TISSUE=Adipose tissue;
RA Miner J.L., Toombs C.F.;
RT "Porcine acylation stimulating protein.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 670-746.
RX PubMed=956663;
RA Corbin N.C., Hugli T.E.;
RT "The primary structure of porcine C3a anaphylatoxin.";
RL J. Immunol. 117:990-995(1976).
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 (By similarity). {ECO:0000250}.
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 -!- FUNCTION: [Acylation stimulating protein]: Adipogenic hormone that
CC stimulates triglyceride (TG) synthesis and glucose transport in
CC adipocytes, regulating fat storage and playing a role in post-prandial
CC TG clearance. Appears to stimulate TG synthesis via activation of the
CC PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the
CC phosphorylation, ARRB2-internalization and recycling of C5AR2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: C3 precursor is first processed by the removal of 4 Arg
CC residues, forming two chains, beta and alpha, linked by a disulfide
CC bond. C3 convertase activates C3 by cleaving the alpha chain, releasing
CC C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). Forms
CC the pro-C3-convertase enzyme complex by binding to Complement factor B
CC Bb fragment (Bb), which is then stabilized by binding CFP, allowing the
CC complex to become active (By similarity). The interaction with Bb is
CC dependent on Mg2+ (By similarity). C3b interacts with CR1 (via Sushi 8
CC and Sushi 9 domains). C3b interacts with CFH. C3d interacts with CFH.
CC C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2).
CC During pregnancy, C3dg exists as a complex (probably a 2:2:2
CC heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4.
CC Interacts with S.aureus immunoglobulin-binding protein sbi, this
CC prevents interaction between C3dg and CR2. Interacts with S.aureus fib.
CC Interacts (both C3a and ASP) with C5AR2; the interaction occurs with
CC higher affinity for ASP, enhancing the phosphorylation and activation
CC of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis of
CC GRP77. {ECO:0000250|UniProtKB:P01024}.
CC -!- INTERACTION:
CC P01025; C7EYC8: gC; Xeno; NbExp=2; IntAct=EBI-11688674, EBI-11688666;
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. C3a is further
CC processed by carboxylases to release the C-termianl arginine residue
CC generating the acylation stimulating protein (ASP). Levels of ASP are
CC increased in adipocytes in the postprandial period and by insulin and
CC dietary chylomicrons (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P01024}.
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DR EMBL; AF154933; AAG40565.1; -; mRNA.
DR EMBL; AJ494748; CAD38823.2; -; Genomic_DNA.
DR EMBL; AF110278; AAC99785.1; -; mRNA.
DR PIR; A01259; A01259.
DR RefSeq; NP_999174.1; NM_214009.1.
DR AlphaFoldDB; P01025; -.
DR SMR; P01025; -.
DR IntAct; P01025; 1.
DR STRING; 9823.ENSSSCP00000027363; -.
DR MEROPS; I39.950; -.
DR PaxDb; P01025; -.
DR PeptideAtlas; P01025; -.
DR PRIDE; P01025; -.
DR GeneID; 397072; -.
DR KEGG; ssc:397072; -.
DR CTD; 718; -.
DR eggNOG; KOG1366; Eukaryota.
DR InParanoid; P01025; -.
DR OrthoDB; 23785at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IDA:AgBase.
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 Fatty acid metabolism; Glycoprotein; Immunity; Inflammatory response;
KW Innate immunity; Lipid metabolism; Phosphoprotein; Reference proteome;
KW Secreted; Signal; Thioester bond.
FT SIGNAL 1..22
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT CHAIN 23..1661
FT /note="Complement C3"
FT /id="PRO_0000419922"
FT CHAIN 23..665
FT /note="Complement C3 beta chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419923"
FT CHAIN 567..665
FT /note="C3-beta-c"
FT /evidence="ECO:0000250"
FT /id="PRO_0000430432"
FT CHAIN 670..1661
FT /note="Complement C3 alpha chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419924"
FT CHAIN 670..746
FT /note="C3a anaphylatoxin"
FT /id="PRO_0000419925"
FT CHAIN 670..745
FT /note="Acylation stimulating protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419926"
FT CHAIN 747..1661
FT /note="Complement C3b alpha' chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419927"
FT CHAIN 747..953
FT /note="Complement C3c alpha' chain fragment 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419928"
FT CHAIN 954..1302
FT /note="Complement C3dg fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419929"
FT CHAIN 954..1000
FT /note="Complement C3g fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419930"
FT CHAIN 1001..1302
FT /note="Complement C3d fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419931"
FT PEPTIDE 1303..1319
FT /note="Complement C3f fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419932"
FT CHAIN 1320..1661
FT /note="Complement C3c alpha' chain fragment 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000419933"
FT DOMAIN 691..726
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1516..1659
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 947..969
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1632..1657
FT /note="Interaction with CFP/properdin"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT SITE 745..746
FT /note="Cleavage; by carboxypeptidases"
FT /evidence="ECO:0000250"
FT SITE 746..747
FT /note="Cleavage; by C3 convertase"
FT /evidence="ECO:0000250"
FT SITE 1301..1302
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000250"
FT SITE 1318..1319
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000250"
FT SITE 1661
FT /note="Coordinates Mg2+ for interaction with Complement
FT factor B Bb fragment"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 70
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 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 966
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 1319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 1571
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT CARBOHYD 937
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 557..814
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 625..660
FT /evidence="ECO:0000250"
FT DISULFID 691..718
FT /evidence="ECO:0000250"
FT DISULFID 692..725
FT /evidence="ECO:0000250"
FT DISULFID 705..726
FT /evidence="ECO:0000250"
FT DISULFID 871..1511
FT /evidence="ECO:0000250"
FT DISULFID 1099..1156
FT /evidence="ECO:0000250"
FT DISULFID 1356..1487
FT /evidence="ECO:0000250"
FT DISULFID 1387..1456
FT /evidence="ECO:0000250"
FT DISULFID 1504..1509
FT /evidence="ECO:0000250"
FT DISULFID 1516..1588
FT /evidence="ECO:0000250"
FT DISULFID 1535..1659
FT /evidence="ECO:0000250"
FT DISULFID 1635..1644
FT /evidence="ECO:0000250"
FT CROSSLNK 1008..1011
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
FT CONFLICT 679
FT /note="D -> N (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 687..688
FT /note="DV -> EL (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 698
FT /note="D -> N (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 713..716
FT /note="QHGD -> HQGN (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="D -> N (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1661 AA; 186807 MW; 4899D0914BE3310C CRC64;
MGSTSGPRLL LLLLTSLPLA LGDPIYTIIT PNVLRLESEE MVVLEAHEGQ GDIRVSVTVH
DFPAKRQVLS SETTTLNNAN NYLSTVNIKI PASKEFKSEK GHKFVTVQAL FGNVQVEKVV
LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VDHKLLPVGQ TIVVTIETPE GIDIKRDSLS
SHNQFGILAL SWNIPELVNM GQWKIRAHYE DAPQQVFSAE FEVKEYVLPS FEVQVEPSEK
FYYIDDPNGL TVNIIARFLY GESVDGTAFV IFGVQDGDQR ISLSQSLTRV PIIDGTGEAT
LSQGVLLNGV HYSSVNDLVG KSIYVSVTVI LNSGSDMVEA ERTGIPIVTS PYQIHFTKTP
KFFKPAMPFD LMVYVTNPDG SPARHIPVVT EDFKVRSLTQ EDGVAKLSIN TPDNRNSLPI
TVRTEKDGIP AARQASKTMH VLPYNTQGNS KNYLHLSLPR VELKPGENLN VNFHLRTDPG
YQDKIRYFTY LIMNKGKLLK VGRQPRESGQ VVVVLPLTIT TDFIPSFRLV AYYTLIAANG
QREVVADSVW VDVKDSCVGT LVVKGGGKQD KQHRPGQQMT LEIQGERGAR VGLVAVDKGV
FVLNKKNKLT QRRIWDVVEK ADIGCTPGSG KDFAGVFTDA GLAFKSSKGL QTPQRADLEC
PKPAARKRRS VQLMEKRMDK LGQYSKDVRR CCEHGMRDNP MKFSCQRRAQ FIQHGDACVK
AFLDCCEYIA KLRQQHSRNK PLGLARSDLD EEIIPEEDII SRSQFPESWL WTIEEFKEPD
KNGISTKTMN VFLKDSITTW EILAVSLSDK KGICVADPYE VVVKQDFFID LRLPYSVVRN
EQVEIRAILY NYREAEDLKV RVELLYNPAF CSLATAKKRH QQTLTVPAKS SVPVPYIIVP
LKTGLQEVEV KAAVYNHFIS DGVKKTLKVV PEGMRVNKTV VTRTLDPEHK GQQGVQREEI
PPADLSDQVP DTESETKILL QGTPVAQMVE DAIDGDRLKH LIQTPSGCGE QNMIGMTPTV
IAVHYLDSTE QWEKFGLEKR QEALELIKKG YTQQLAFRQK NSAFAAFQDR LSSTLLTAYV
VKVFAMAANL IAIDSQVLCG AVKWLILEKQ KPDGVFEENG PVIHQEMIGG FKNTEEKDVS
LTAFVLIALQ EAKDICEPQV NSLLRSINKA RDFLADYYLE LKRPYTVAIA GYALALSDKL
DEPFLNKLLS TAKERNRWEE PGQKLHNVEA TSYALLALLV VKDFDSVPPI VRWLNEQRYY
GGGYGSTQAT FMVFQALAQY QKDVPDHKDL NLDVSIHLPS RSAPVRHRIL WESASLLRSE
ETKENEGFTL IAEGKGQGTL SVVTMYHGKA KGKTTCKKFD LKVSIHPAPE PVKKPQEAKS
SMVLDICTRY LGNQDATMSI LDISMMTGFS PDTEDLKLLS TGVDRYISKY ELNKALSNKN
TLIIYLDKIS HTLEDCISFK VHQYFNVGLI QPGSVKVYSY YNLDESCTRF YHPEKEDGML
NKLCHKEMCR CAEENCFMHH DEEEVTLDDR LERACEPGVD YVYKTRLLKK ELSDDFDDYI
MVIEQIIKSG SDEVQVGQER RFISHIKCRE ALKLKEGGHY LVWGVSSDLW GEKPNISYII
GKDTWVELWP DGDVCQDEEN QKQCQDLANF SENMVVFGCP N
