CO3_RABIT
ID CO3_RABIT Reviewed; 726 AA.
AC P12247;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 25-MAY-2022, entry version 116.
DE RecName: Full=Complement C3 alpha chain;
DE Flags: Fragment;
GN Name=C3;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3019881; DOI=10.3109/08820138609052955;
RA Kusano M., Choi N.H., Tomita M., Yamamoto K., Migita S., Sekiya T.,
RA Nishimura S.;
RT "Nucleotide sequence of cDNA and derived amino acid sequence of rabbit
RT complement component C3 alpha-chain.";
RL Immunol. Invest. 15:365-378(1986).
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 -!- 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) (By
CC similarity). Forms the pro-C3-convertase enzyme complex by binding to
CC Complement factor B Bb fragment (Bb), which is then stabilized by
CC binding CFP, allowing the complex to become active (By similarity). The
CC interaction with Bb is dependent on Mg2+ (By similarity). C3b interacts
CC with CR1 (via Sushi 8 and Sushi 9 domains). C3b interacts with CFH. C3d
CC interacts with CFH. C3dg interacts with CR2 (via the N-terminal Sushi
CC domains 1 and 2). During pregnancy, C3dg exists as a complex (probably
CC a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with
CC VSIG4. 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 (By similarity). {ECO:0000250|UniProtKB:P01024}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P01024}.
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DR EMBL; M32434; AAA31190.1; -; mRNA.
DR PIR; A27602; A27602.
DR RefSeq; NP_001075755.1; NM_001082286.1.
DR AlphaFoldDB; P12247; -.
DR SMR; P12247; -.
DR STRING; 9986.ENSOCUP00000007209; -.
DR PRIDE; P12247; -.
DR GeneID; 100009121; -.
DR KEGG; ocu:100009121; -.
DR CTD; 718; -.
DR eggNOG; KOG1366; Eukaryota.
DR InParanoid; P12247; -.
DR OrthoDB; 23785at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005615; C:extracellular space; 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 CDD; cd03583; NTR_complement_C3; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR035711; Complement_C3-like.
DR InterPro; IPR019742; MacrogloblnA2_CS.
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; PF07677; A2M_recep; 1.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF07678; TED_complement; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SMART; SM00643; C345C; 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; PS50189; NTR; 1.
PE 2: Evidence at transcript level;
KW Complement alternate pathway; Complement pathway; Disulfide bond;
KW Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW Phosphoprotein; Reference proteome; Secreted; Thioester bond.
FT CHAIN <1..726
FT /note="Complement C3 alpha chain"
FT /id="PRO_0000005936"
FT DOMAIN 581..724
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 697..722
FT /note="Interaction with CFP/properdin"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT SITE 726
FT /note="Coordinates Mg2+ for interaction with Complement
FT factor B Bb fragment"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT MOD_RES 636
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01024"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 680
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 581..653
FT /evidence="ECO:0000250"
FT DISULFID 600..724
FT /evidence="ECO:0000250"
FT CROSSLNK 73..76
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 726 AA; 81844 MW; F4B4C35D461300E9 CRC64;
MNKTVAVRTL DPENLGQGGV QKEEIPSADI SDQVPGTESE TKILLQGTPV AQMTEDAIDG
ERLKHLIVTG SGCGEQNMIA MTHTVIAVHY LDHTEQWDKF SLEKRQEALE LIKKGYTQQL
AFKQPNSAYA AFLNRAPSTW LTAYVVKVFS LAVNLIAIDS QVLCGAVKWL IMEKQKPDGV
FQEDAPVIHQ EMIGGQRNSV EKERALTAFV LIALQEAREI CEEQVNSLAA SINKSRDFLA
ANYMNLQRPY SVAIAAYAWA QQDKLRGAFL NKFLSKAKEK NRWEEPGQRL YNVEASSYAL
LALLLLRDFD SVPPVVRWLN EQRYYGGGYG STQATFMGFQ ALAQYQTDVP DHKDLNMVVS
IQLPSRSSPV KHRIVWDSAS LLRSEETKEN QGFSLTAQGK GQGTLSVVTT YFAKVKGKVT
CKKFDLRVNI KTAPETVKKP QDAKSTMILG HCTRYLGDED ATMSILDISM MTGFVPDTDD
LNLLSTGVDR YISKYELNKA FSNKNTLIIY LDKISHSREE CLAFKVHQYF NVGLIQPGAV
KVYSYYNLEE TCTQFYHPEK EDGMLSKLCH KEMCRCAEEN CFMQQLDEKI TLNDRLDKAC
EPGLDYVYKT KLVQVERADD FDEYLMVVEN TIKSGSDEVQ AGQPAPFISH IKCRDALKLK
DGKHYLMWGL SSDPVGEKPN TSYIIGKDTW VEFWPEKEEC QDEENQKHCE DLGAFAESMV
VFGCPN
