Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P01026 (CO3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Protein attributes

Sequence length1663 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

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. Acts as a chemoattractant for neutophils. Ref.2

Neutrophil chemotactic factor-2 acts as a chemoattractant for neurophils. Ref.2

Acylation stimulating protein: adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2 By similarity. Ref.2

Subunit structure

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.

Subcellular location

Secreted.

Post-translational modification

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 carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by dietary chylomicrons By similarity.

Phosphorylation sites are present in the extracellular medium By similarity.

Sequence similarities

Contains 1 anaphylatoxin-like domain.

Contains 1 NTR domain.

Ontologies

Keywords
   Biological processChemotaxis
Complement alternate pathway
Complement pathway
Fatty acid metabolism
Immunity
Inflammatory response
Innate immunity
Lipid metabolism
   Cellular componentSecreted
   DomainSignal
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Thioester bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Inferred from mutant phenotype PubMed 15956288. Source: RGD

chemotaxis

Inferred from electronic annotation. Source: UniProtKB-KW

complement activation

Inferred from direct assay PubMed 20712003. Source: RGD

complement activation, alternative pathway

Inferred from electronic annotation. Source: UniProtKB-KW

complement activation, classical pathway

Traceable author statement PubMed 16996480. Source: RGD

fatty acid metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 18178156. Source: RGD

positive regulation of G-protein coupled receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of developmental growth

Inferred from direct assay PubMed 20712003. Source: RGD

positive regulation of glucose transport

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of lipid storage

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of triglyceride biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

response to estradiol

Inferred from expression pattern PubMed 12370124. Source: RGD

response to estrogen

Inferred from expression pattern PubMed 11846090. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 11566438. Source: RGD

response to magnesium ion

Inferred from expression pattern PubMed 12759143. Source: RGD

response to progesterone

Inferred from expression pattern PubMed 11566438. Source: RGD

tolerance induction

Inferred from expression pattern PubMed 16555329. Source: RGD

   Cellular_componentextracellular space

Inferred from direct assay PubMed 20712003. Source: RGD

   Molecular_functionC5L2 anaphylatoxin chemotactic receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

cofactor binding

Inferred from physical interaction PubMed 15215199. Source: RGD

endopeptidase inhibitor activity

Inferred from electronic annotation. Source: InterPro

lipid binding

Inferred from direct assay PubMed 11305612. Source: RGD

protein binding

Inferred from physical interaction PubMed 12871224. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 16631639Complement C3
PRO_0000005937
Chain25 – 666642Complement C3 beta chain
PRO_0000005938
Chain568 – ?Neutrophil chemotactic factor-2PRO_0000395292
Chain671 – 1663993Complement C3 alpha chain
PRO_0000005939
Chain671 – 74878C3a anaphylatoxin
PRO_0000005940
Chain671 – 74777Acylation stimulating protein By similarity
PRO_0000419937
Chain749 – 1663915Complement C3b alpha' chain
PRO_0000005941
Chain749 – 959211Complement C3c alpha' chain fragment 1
PRO_0000273950
Chain960 – 1303344Complement C3dg fragment By similarity
PRO_0000273951
Chain960 – 100142Complement C3g fragment By similarity
PRO_0000273952
Chain1002 – 1303302Complement C3d fragment By similarity
PRO_0000273953
Peptide1304 – 132017Complement C3f fragment By similarity
PRO_0000273954
Chain1321 – 1663343Complement C3c alpha' chain fragment 2 By similarity
PRO_0000273955

Regions

Domain693 – 72836Anaphylatoxin-like
Domain1518 – 1661144NTR
Region1424 – 145633Properdin-binding By similarity

Sites

Site747 – 7482Cleavage; by carboxypeptidases By similarity
Site748 – 7492Cleavage; by C3 convertase
Site959 – 9602Cleavage; by factor I Potential
Site1303 – 13042Cleavage; by factor I By similarity
Site1320 – 13212Cleavage; by factor I By similarity

Amino acid modifications

Glycosylation9391N-linked (GlcNAc...) Probable
Glycosylation16171N-linked (GlcNAc...) Probable
Disulfide bond558 ↔ 816Interchain (between beta and alpha chains) By similarity
Disulfide bond626 ↔ 661 By similarity
Disulfide bond693 ↔ 720 By similarity
Disulfide bond694 ↔ 727 By similarity
Disulfide bond707 ↔ 728 By similarity
Disulfide bond873 ↔ 1513 By similarity
Disulfide bond1101 ↔ 1158 By similarity
Disulfide bond1358 ↔ 1489 By similarity
Disulfide bond1389 ↔ 1458 By similarity
Disulfide bond1506 ↔ 1511 By similarity
Disulfide bond1518 ↔ 1590 By similarity
Disulfide bond1537 ↔ 1661 By similarity
Cross-link1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln) By similarity

Experimental info

Sequence conflict7041P → K in AAG00532. Ref.4
Sequence conflict721 – 7222LK → KL AA sequence Ref.3

Secondary structure

................................. 1663
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01026 [UniParc].

Last modified August 1, 1990. Version 3.
Checksum: 2F87CCB143CDD4BC

FASTA1,663186,460
        10         20         30         40         50         60 
MGPTSGSQLL VLLLLLASSL LALGSPMYSI ITPNVLRLES EETFILEAHD AQGDVPVTVT 

        70         80         90        100        110        120 
VQDFLKKQVL TSEKTVLTGA TGHLNRVFIK IPASKEFNAD KGHKYVTVVA NFGATVVEKA 

       130        140        150        160        170        180 
VLVSFQSGYL FIQTDKTIYT PGSTVFYRIF TVDNNLLPVG KTVVIVIETP DGVPIKRDIL 

       190        200        210        220        230        240 
SSHNQYGILP LSWNIPELVN MGQWKIRAFY EHAPKQTFSA EFEVKEYVLP SFEVLVEPTE 

       250        260        270        280        290        300 
KFYYIHGPKG LEVSITARFL YGKNVDGTAF VIFGVQDEDK KISLALSLTR VLIEDGSGEA 

       310        320        330        340        350        360 
VLSRKVLMDG VRPSSPEALV GKSLYVSVTV ILHSGSDMVE AERSGIPIVT SPYQIHFTKT 

       370        380        390        400        410        420 
PKFFKPAMPF DLMVFVTNPD GSPARRVPVV TQGSDAQALT QDDGVAKLSV NTPNNRQPLT 

       430        440        450        460        470        480 
ITVSTKKEGI PDARQATRTM QAQPYSTMHN SNNYLHLSVS RVELKPGDNL NVNFHLRTDA 

       490        500        510        520        530        540 
GQEAKIRYYT YLVMNKGKLL KAGRQVREPG QDLVVLSLPI TPEFIPSFRL VAYYTLIGAN 

       550        560        570        580        590        600 
GQREVVADSV WVDVKDSCVG TLVVKGDPRD NRQPAPGHQT TLRIEGNQGA RVGLVAVDKG 

       610        620        630        640        650        660 
VFVLNKKNKL TQSKIWDVVE KADIGCTPGS GKNYAGVFMD AGLTFKTNQG LQTDQREDPE 

       670        680        690        700        710        720 
CAKPAARRRR SVQLMERRMD KAGQYTDKGL RKCCEDGMRD IPMPYSCQRR ARLITQGESC 

       730        740        750        760        770        780 
LKAFMDCCNY ITKLREQHRR DHVLGLARSD VDEDIIPEED IISRSHFPES WLWTIEELKE 

       790        800        810        820        830        840 
PEKNGISTKV MNIFLKDSIT TWEILAVSLS DKKGICVADP YEITVMQDFF IDLRLPYSVV 

       850        860        870        880        890        900 
RNEQVEIRAV LFNYREQEKL KVRVELLHNP AFCSMATAKK RYYQTIEIPP KSSVAVPYVI 

       910        920        930        940        950        960 
VPLKIGLQEV EVKAAVFNHF ISDGVKKILK VVPEGMRVNK TVAVRTLDPE HLNQGGVQRE 

       970        980        990       1000       1010       1020 
DVNAADLSDQ VPDTDSETRI LLQGTPVAQM AEDAVDGERL KHLIVTPSGC GEQNMIGMTP 

      1030       1040       1050       1060       1070       1080 
TVIAVHYLDQ TEQWEKFGLE KRQEALELIK KGYTQQLAFK QPISAYAAFN NRPPSTWLTA 

      1090       1100       1110       1120       1130       1140 
MWSRSFSLAA NLIAIDSQVL CGAVKWLILE KQKPDGVFQE DGPVIHQEMI GGFRNTKEAD 

      1150       1160       1170       1180       1190       1200 
VSLTAFVLIA LQEARDICEG QVNSLPGSIN KAGEYLEASY LNLQRPYTVA IAGYALALMN 

      1210       1220       1230       1240       1250       1260 
KLEEPYLTKF LNTAKDRNRW EEPGQQLYNV EATSYALLAL LLLKDFDSVP PVVRWLNDER 

      1270       1280       1290       1300       1310       1320 
YYGGGYGSTQ ATFMVFQALA QYRADVPDHK DLNMDVSLHL PSRSSPTVFR LLWESGSLLR 

      1330       1340       1350       1360       1370       1380 
SEETKQNEGF SLTAKGKGQG TLSVVTVYHA KVKGKTTCKK FDLRVTIKPA PETAKKPQDA 

      1390       1400       1410       1420       1430       1440 
KSSMILDICT RYLGDVDATM SILDISMMTG FIPDTNDLEL LSSGVDRYIS KYEMDKAFSN 

      1450       1460       1470       1480       1490       1500 
KNTLIIYLEK ISHSEEDCLS FKVHQFFNVG LIQPGSVKVY SYYNLEESCT RFYHPEKDDG 

      1510       1520       1530       1540       1550       1560 
MLSKLCHNEM CRCAEENCFM HQSQDQVSLN ERLDKACEPG VDYVYKTKLT TIELSDDFDE 

      1570       1580       1590       1600       1610       1620 
YIMTIEQVIK SGSDEVQAGQ ERRFISHVKC RNALKLQKGK QYLMWGLSSD LWGEKPNTSY 

      1630       1640       1650       1660 
IIGKDTWVEH WPEAEERQDQ KNQKQCEDLG AFTETMVVFG CPN 

« Hide

References

[1]"Nucleotide and deduced amino acid sequence of rat complement C3."
Misumi Y., Sohda M., Ikehara Y.
Nucleic Acids Res. 18:2178-2178(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar.
Tissue: Liver.
[2]"Complement component C3-derived neutrophil chemotactic factors purified from exudate of rat carrageenin-induced inflammation."
Nakagawa H., Komorita N.
Biochem. Biophys. Res. Commun. 194:1181-1187(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 568-592 AND 671-687, FUNCTION.
Tissue: Neutrophil.
[3]"Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a)."
Jacobs J.W., Rubin J.S., Hugli T.E., Bogardt R.A. Jr., Mariz I.K., Daniels J.S., Daughaday W.H., Bradshaw R.A.
Biochemistry 17:5031-5038(1978) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 671-748.
[4]"Nucleotide and deduced amino acid sequence of rat complement component C3a derived from Sprague-Dawley strain."
Wahrmann M., Krieger S., Liewehr A.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 671-748.
Strain: Sprague-Dawley.
Tissue: Liver.
[5]"Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment."
Zanotti G., Bassetto A., Battistutta R., Folli C., Arcidiaco P., Stoppini M., Berni R.
Biochim. Biophys. Acta 1478:232-238(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 960-969, X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 1010-1286.
[6]"Estrogen regulation of tissue-specific expression of complement C3."
Sundstrom S.A., Komm B.S., Ponce-De-Leon H., Yi Z., Teuscher C., Lyttle C.R.
J. Biol. Chem. 264:16941-16947(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1316-1595.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52477 mRNA. Translation: CAA36716.1.
AF286158 mRNA. Translation: AAG00532.1.
M29866 mRNA. Translation: AAA40837.1.
PIRC3RT. S15764.
RefSeqNP_058690.2. NM_016994.2.
UniGeneRn.11378.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QQFX-ray1.45A1010-1286[»]
1QSJX-ray1.90A/B/C/D1010-1286[»]
ProteinModelPortalP01026.
SMRP01026. Positions 25-663, 672-1663.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246419. 1 interaction.

Protein family/group databases

MEROPSI39.950.

PTM databases

PhosphoSiteP01026.

Proteomic databases

PRIDEP01026.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24232.
KEGGrno:24232.

Organism-specific databases

CTD718.
RGD2232. C3.

Phylogenomic databases

HOVERGENHBG005110.
KOK03990.
PhylomeDBP01026.

Gene expression databases

GenevestigatorP01026.

Family and domain databases

Gene3D1.20.91.20. 1 hit.
1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR000020. Anaphylatoxin/fibulin.
IPR018081. Anaphylatoxin_comp_syst.
IPR001840. Anaphylatoxn_comp_syst_dom.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamPF00207. 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.
[Graphical view]
PRINTSPR00004. ANAPHYLATOXN.
SMARTSM00104. ANATO. 1 hit.
SM00643. C345C. 1 hit.
[Graphical view]
SUPFAMSSF47686. SSF47686. 1 hit.
SSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF50242. SSF50242. 1 hit.
PROSITEPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
PS01177. ANAPHYLATOXIN_1. 1 hit.
PS01178. ANAPHYLATOXIN_2. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01026.
NextBio602683.

Entry information

Entry nameCO3_RAT
AccessionPrimary (citable) accession number: P01026
Secondary accession number(s): Q9ET19, Q9QV57, Q9QV58
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 1, 1990
Last modified: June 11, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references