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P01024 (CO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C3
Alternative name(s):
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1

Cleaved into the following 10 chains:

  1. Complement C3 beta chain
  2. Complement C3 alpha chain
  3. C3a anaphylatoxin
  4. Complement C3b alpha' chain
  5. Complement C3c alpha' chain fragment 1
  6. Complement C3dg fragment
  7. Complement C3g fragment
  8. Complement C3d fragment
  9. Complement C3f fragment
  10. Complement C3c alpha' chain fragment 2
Gene names
Name:C3
Synonyms:CPAMD1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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.

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.

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). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4. C3b interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 2 (HHV-2) envelope glycoprotein C; this interaction inhibits the activation of the complement system. Interacts with S.aureus immunoglobulin-binding protein sbi, this prevents interaction between C3dg and CR2. Interacts with S.aureus fib. Ref.6 Ref.9 Ref.18 Ref.19 Ref.29 Ref.30

Subcellular location

Secreted.

Tissue specificity

Plasma. Ref.17

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.

Phosphorylation sites are present in the extracelllular medium.

Polymorphism

There are two alleles: C3S (C3 slow), the most common allele in all races and C3F (C3 fast), relatively frequent in Caucasoids, less common in Black Americans, extremely rare in Orientals.

Involvement in disease

Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:613779]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis. Ref.21 Ref.22 Ref.23 Ref.34 Ref.35

Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:611378]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Ref.36

Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:612925]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Ref.37 Ref.38

Sequence similarities

Contains 1 anaphylatoxin-like domain.

Contains 1 NTR domain.

Caution

According to Ref.30, the interaction surface between C3 and CR2 reported in Ref.22 is artifactual and can be ascribed to the presence of zinc acetate in the buffer.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VSIG4Q9Y279-15EBI-905851,EBI-903144
VSIG4Q9Y279-22EBI-905851,EBI-903148

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Chain23 – 16631641Complement C3
PRO_0000005907
Chain23 – 667645Complement C3 beta chain
PRO_0000005908
Chain672 – 1663992Complement C3 alpha chain
PRO_0000005909
Chain672 – 74877C3a anaphylatoxin
PRO_0000005910
Chain749 – 1663915Complement C3b alpha' chain
PRO_0000005911
Chain749 – 954206Complement C3c alpha' chain fragment 1
PRO_0000005912
Chain955 – 1303349Complement C3dg fragment
PRO_0000005913
Chain955 – 100147Complement C3g fragment
PRO_0000005914
Chain1002 – 1303302Complement C3d fragment
PRO_0000005915
Peptide1304 – 132017Complement C3f fragment
PRO_0000005916
Chain1321 – 1663343Complement C3c alpha' chain fragment 2
PRO_0000273948

Regions

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

Sites

Site748 – 7492Cleavage; by C3 convertase
Site954 – 9552Cleavage; by factor I Potential
Site1303 – 13042Cleavage; by factor I
Site1320 – 13212Cleavage; by factor I

Amino acid modifications

Modified residue2971Phosphoserine Ref.17
Modified residue4891Phosphotyrosine By similarity
Modified residue15711Phosphoserine Ref.17
Modified residue15731Phosphoserine Ref.17
Glycosylation851N-linked (GlcNAc...) Ref.1 Ref.12 Ref.14 Ref.15 Ref.16 Ref.26 Ref.27
Glycosylation9391N-linked (GlcNAc...) Ref.13 Ref.14 Ref.26
Glycosylation16171N-linked (GlcNAc...) Ref.14
Disulfide bond559 ↔ 816Interchain (between beta and alpha chains) Ref.11 Ref.27
Disulfide bond627 ↔ 662 Ref.11 Ref.27
Disulfide bond693 ↔ 720 Ref.11 Ref.27
Disulfide bond694 ↔ 727 Ref.11 Ref.27
Disulfide bond707 ↔ 728 Ref.11 Ref.27
Disulfide bond873 ↔ 1513 Ref.11 Ref.27
Disulfide bond1101 ↔ 1158 Ref.11 Ref.27
Disulfide bond1358 ↔ 1489 Ref.11 Ref.27
Disulfide bond1389 ↔ 1458 Ref.11 Ref.27
Disulfide bond1506 ↔ 1511 Ref.11 Ref.27
Disulfide bond1518 ↔ 1590 Ref.11 Ref.27
Disulfide bond1537 ↔ 1661 Ref.11 Ref.27
Disulfide bond1637 ↔ 1646 Ref.11 Ref.27
Cross-link1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)

Natural variations

Natural variant1021R → G in allele C3F; associated with ARMD9. Ref.2 Ref.33 Ref.36
Corresponds to variant rs2230199 [ dbSNP | Ensembl ].
VAR_001983
Natural variant3141P → L. Ref.1 Ref.2 Ref.33
Corresponds to variant rs1047286 [ dbSNP | Ensembl ].
VAR_001984
Natural variant4691E → D.
Corresponds to variant rs11569422 [ dbSNP | Ensembl ].
VAR_020262
Natural variant5491D → N in C3D; impairs secretion. Ref.34
VAR_001985
Natural variant5921R → Q in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. Ref.37
VAR_063213
Natural variant5921R → W in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. Ref.37
VAR_063214
Natural variant6031F → V in AHUS5. Ref.38
VAR_063654
Natural variant7351R → W in AHUS5. Ref.37
VAR_063215
Natural variant8631R → K. Ref.2
Corresponds to variant rs11569472 [ dbSNP | Ensembl ].
VAR_019206
Natural variant10421R → L in AHUS5. Ref.38
VAR_063655
Natural variant10941A → V in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. Ref.37
VAR_063216
Natural variant11151D → N in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. Ref.37
VAR_063217
Natural variant11581C → W in AHUS5. Ref.37
VAR_063218
Natural variant11611Q → K in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. Ref.37
VAR_063219
Natural variant12161D → N in C3S. Ref.31
VAR_022761
Natural variant12241G → D. Ref.2
Corresponds to variant rs11569534 [ dbSNP | Ensembl ].
VAR_019207
Natural variant13201R → Q in C3D; allotype C3'F02'; may inhibit IC3B synthesis. Ref.35
VAR_001986
Natural variant13671I → T. Ref.2
Corresponds to variant rs11569541 [ dbSNP | Ensembl ].
VAR_019208
Natural variant14641H → D in AHUS5. Ref.37
VAR_063220
Natural variant15211Q → R.
Corresponds to variant rs7256789 [ dbSNP | Ensembl ].
VAR_029792
Natural variant16011H → N.
Corresponds to variant rs1803225 [ dbSNP | Ensembl ].
VAR_029793
Natural variant16191S → R.
Corresponds to variant rs2230210 [ dbSNP | Ensembl ].
VAR_029326

Experimental info

Mutagenesis10291D → A: Minor effect on binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis10301E → A: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis10321E → A: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis10351E → A: No effect on binding of C3d to CR2. Ref.10 Ref.18
Mutagenesis10421R → M: Impaired binding of C3d to CR2. Ref.10 Ref.18
Mutagenesis1108 – 11092IL → RR: Impaired binding of C3d to CR2; when associated with A-1163. Ref.10
Mutagenesis11101E → A: No effect on binding of C3d to CR2. Ref.10 Ref.19
Mutagenesis11151D → A: No effect on binding of C3d to CR2. Ref.10 Ref.19
Mutagenesis11211D → A: No effect on binding of C3d to CR2. Ref.10 Ref.19
Mutagenesis11401D → A: No effect on binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis11531E → A: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis11561D → A: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis11591E → A: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis11601E → A: Minor effect on binding of C3d to CR2. Ref.10 Ref.18 Ref.19
Mutagenesis11631N → A: No effect on binding of C3d to CR2. Impaired binding of C3d to CR2; when associated with 1108-R-R-1109. Ref.10 Ref.18 Ref.19 Ref.22
Mutagenesis11631N → R: Impaired binding of C3d to CR2. Ref.10 Ref.18 Ref.19 Ref.22
Mutagenesis12841K → A: Impaired binding of C3d to CR2. Ref.10 Ref.18
Sequence conflict6811D → N AA sequence Ref.5
Sequence conflict7001E → Q AA sequence Ref.5
Sequence conflict10261H → S AA sequence Ref.7

Secondary structure

1 ...................................................................................................................................................................................................................................................................... 1663
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01024 [UniParc].

Last modified December 12, 2006. Version 2.
Checksum: 30C2832A9E75FFC4

FASTA1,663187,148
        10         20         30         40         50         60 
MGPTSGPSLL LLLLTHLPLA LGSPMYSIIT PNILRLESEE TMVLEAHDAQ GDVPVTVTVH 

        70         80         90        100        110        120 
DFPGKKLVLS SEKTVLTPAT NHMGNVTFTI PANREFKSEK GRNKFVTVQA TFGTQVVEKV 

       130        140        150        160        170        180 
VLVSLQSGYL FIQTDKTIYT PGSTVLYRIF TVNHKLLPVG RTVMVNIENP EGIPVKQDSL 

       190        200        210        220        230        240 
SSQNQLGVLP LSWDIPELVN MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE 

       250        260        270        280        290        300 
KFYYIYNEKG LEVTITARFL YGKKVEGTAF VIFGIQDGEQ RISLPESLKR IPIEDGSGEV 

       310        320        330        340        350        360 
VLSRKVLLDG VQNPRAEDLV GKSLYVSATV ILHSGSDMVQ AERSGIPIVT SPYQIHFTKT 

       370        380        390        400        410        420 
PKYFKPGMPF DLMVFVTNPD GSPAYRVPVA VQGEDTVQSL TQGDGVAKLS INTHPSQKPL 

       430        440        450        460        470        480 
SITVRTKKQE LSEAEQATRT MQALPYSTVG NSNNYLHLSV LRTELRPGET LNVNFLLRMD 

       490        500        510        520        530        540 
RAHEAKIRYY TYLIMNKGRL LKAGRQVREP GQDLVVLPLS ITTDFIPSFR LVAYYTLIGA 

       550        560        570        580        590        600 
SGQREVVADS VWVDVKDSCV GSLVVKSGQS EDRQPVPGQQ MTLKIEGDHG ARVVLVAVDK 

       610        620        630        640        650        660 
GVFVLNKKNK LTQSKIWDVV EKADIGCTPG SGKDYAGVFS DAGLTFTSSS GQQTAQRAEL 

       670        680        690        700        710        720 
QCPQPAARRR RSVQLTEKRM DKVGKYPKEL RKCCEDGMRE NPMRFSCQRR TRFISLGEAC 

       730        740        750        760        770        780 
KKVFLDCCNY ITELRRQHAR ASHLGLARSN LDEDIIAEEN IVSRSEFPES WLWNVEDLKE 

       790        800        810        820        830        840 
PPKNGISTKL MNIFLKDSIT TWEILAVSMS DKKGICVADP FEVTVMQDFF IDLRLPYSVV 

       850        860        870        880        890        900 
RNEQVEIRAV LYNYRQNQEL KVRVELLHNP AFCSLATTKR RHQQTVTIPP KSSLSVPYVI 

       910        920        930        940        950        960 
VPLKTGLQEV EVKAAVYHHF ISDGVRKSLK VVPEGIRMNK TVAVRTLDPE RLGREGVQKE 

       970        980        990       1000       1010       1020 
DIPPADLSDQ VPDTESETRI LLQGTPVAQM TEDAVDAERL KHLIVTPSGC GEQNMIGMTP 

      1030       1040       1050       1060       1070       1080 
TVIAVHYLDE TEQWEKFGLE KRQGALELIK KGYTQQLAFR QPSSAFAAFV KRAPSTWLTA 

      1090       1100       1110       1120       1130       1140 
YVVKVFSLAV NLIAIDSQVL CGAVKWLILE KQKPDGVFQE DAPVIHQEMI GGLRNNNEKD 

      1150       1160       1170       1180       1190       1200 
MALTAFVLIS LQEAKDICEE QVNSLPGSIT KAGDFLEANY MNLQRSYTVA IAGYALAQMG 

      1210       1220       1230       1240       1250       1260 
RLKGPLLNKF LTTAKDKNRW EDPGKQLYNV EATSYALLAL LQLKDFDFVP PVVRWLNEQR 

      1270       1280       1290       1300       1310       1320 
YYGGGYGSTQ ATFMVFQALA QYQKDAPDHQ ELNLDVSLQL PSRSSKITHR IHWESASLLR 

      1330       1340       1350       1360       1370       1380 
SEETKENEGF TVTAEGKGQG TLSVVTMYHA KAKDQLTCNK FDLKVTIKPA PETEKRPQDA 

      1390       1400       1410       1420       1430       1440 
KNTMILEICT RYRGDQDATM SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD 

      1450       1460       1470       1480       1490       1500 
RNTLIIYLDK VSHSEDDCLA FKVHQYFNVE LIQPGAVKVY AYYNLEESCT RFYHPEKEDG 

      1510       1520       1530       1540       1550       1560 
KLNKLCRDEL CRCAEENCFI QKSDDKVTLE ERLDKACEPG VDYVYKTRLV KVQLSNDFDE 

      1570       1580       1590       1600       1610       1620 
YIMAIEQTIK SGSDEVQVGQ QRTFISPIKC REALKLEEKK HYLMWGLSSD FWGEKPNLSY 

      1630       1640       1650       1660 
IIGKDTWVEH WPEEDECQDE ENQKQCQDLG AFTESMVVFG CPN

« Hide

References

« Hide 'large scale' references
[1]"Human complement component C3: cDNA coding sequence and derived primary structure."
de Bruijn M.H.L., Fey G.H.
Proc. Natl. Acad. Sci. U.S.A. 82:708-712(1985) [PubMed: 2579379] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-314.
[2]SeattleSNPs variation discovery resource
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-102; LEU-314; LYS-863; ASP-1224 AND THR-1367.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Human anaphylatoxin (C3a) from the third component of complement. Primary structure."
Hugli T.E.
J. Biol. Chem. 250:8293-8301(1975) [PubMed: 1238393] [Abstract]
Cited for: PROTEIN SEQUENCE OF 672-748.
[6]"Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma."
Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T., Gleich G.J., Sottrup-Jensen L.
J. Biol. Chem. 270:13645-13651(1995) [PubMed: 7539791] [Abstract]
Cited for: PROTEIN SEQUENCE OF 955-966, SUBUNIT.
Tissue: Serum.
[7]"Third component of human complement: localization of the internal thiolester bond."
Thomas M.L., Janatova J., Gray W.R., Tack B.F.
Proc. Natl. Acad. Sci. U.S.A. 79:1054-1058(1982) [PubMed: 6175959] [Abstract]
Cited for: PROTEIN SEQUENCE OF 988-1036.
[8]"A 34-amino acid peptide of the third component of complement mediates properdin binding."
Daoudaki M.E., Becherer J.D., Lambris J.D.
J. Immunol. 140:1577-1580(1988) [PubMed: 3279119] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1409-1563.
[9]"Complement component C3b binds directly to purified glycoprotein C of herpes simplex virus types 1 and 2."
Eisenberg R.J., Ponce de Leon M., Friedman H.M., Fries L.F., Frank M.M., Hastings J.C., Cohen G.H.
Microb. Pathog. 3:423-435(1987) [PubMed: 2849025] [Abstract]
Cited for: INTERACTION WITH HERPES SIMPLEX VIRUS HHV-1 AND HHV-2 GYCOPROTEIN C.
[10]"Structural requirements for thioester bond formation in human complement component C3. Reassessment of the role of thioester bond integrity on the conformation of C3."
Isaac L., Isenman D.E.
J. Biol. Chem. 267:10062-10069(1992) [PubMed: 1577777] [Abstract]
Cited for: MUTAGENESIS OF THE THIOESTER BOND REGION.
[11]"Disulfide bridges in human complement component C3b."
Dolmer K., Sottrup-Jensen L.
FEBS Lett. 315:85-90(1993) [PubMed: 8416818] [Abstract]
Cited for: DISULFIDE BONDS.
[12]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract]
Cited for: GLYCOSYLATION AT ASN-85.
[13]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed: 14760718] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-939, MASS SPECTROMETRY.
Tissue: Plasma.
[14]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85; ASN-939 AND ASN-1617, MASS SPECTROMETRY.
Tissue: Plasma.
[15]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85, MASS SPECTROMETRY.
Tissue: Platelet.
[16]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85, MASS SPECTROMETRY.
Tissue: Liver.
[17]"An initial characterization of the serum phosphoproteome."
Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A., Liotta L.A., Petricoin E.F. III
J. Proteome Res. 8:5523-5531(2009) [PubMed: 19824718] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297; SER-1571 AND SER-1573, TISSUE SPECIFICITY, MASS SPECTROMETRY.
Tissue: Serum.
[18]"Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: implications for the controversy regarding the CR2/C3d cocrystal structure."
Isenman D.E., Leung E., Mackay J.D., Bagby S., van den Elsen J.M.
J. Immunol. 184:1946-1955(2010) [PubMed: 20083651] [Abstract]
Cited for: MUTAGENESIS OF ASP-1029; GLU-1030; GLU-1032; GLU-1035; ARG-1042; ASP-1140; GLU-1153; ASP-1156; GLU-1159; GLU-1160; ASN-1163 AND LYS-1284, INTERACTION WITH CR2 AND S.AUREUS SBI.
[19]"Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking."
Shaw C.D., Storek M.J., Young K.A., Kovacs J.M., Thurman J.M., Holers V.M., Hannan J.P.
J. Mol. Biol. 404:697-710(2010) [PubMed: 20951140] [Abstract]
Cited for: MUTAGENESIS OF ASP-1029; GLU-1030; GLU-1032; GLU-1110; ASP-1115; ASP-1121; ASP-1140; GLU-1153; ASP-1156; GLU-1159; GLU-1160 AND ASN-1163, INTERACTION WITH CR2.
[20]"Secondary structure of complement component C3a anaphylatoxin in solution as determined by NMR spectroscopy: differences between crystal and solution conformations."
Nettesheim D.G., Edalji R.P., Mollison K.W., Greer J., Zuiderweg E.R.P.
Proc. Natl. Acad. Sci. U.S.A. 85:5036-5040(1988) [PubMed: 3260670] [Abstract]
Cited for: STRUCTURE BY NMR OF C3A.
[21]"X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2."
Nagar B., Jones R.G., Diefenbach R.J., Isenman D.E., Rini J.M.
Science 280:1277-1281(1998) [PubMed: 9596584] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D.
[22]"Structure of complement receptor 2 in complex with its C3d ligand."
Szakonyi G., Guthridge J.M., Li D., Young K., Holers V.M., Chen X.S.
Science 292:1725-1728(2001) [PubMed: 11387479] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D IN COMPLEX WITH CR2, MUTAGENESIS OF 1108-ILE-LEU-1109 AND ASN-1163.
[23]"Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study."
Gilbert H.E., Eaton J.T., Hannan J.P., Holers V.M., Perkins S.J.
J. Mol. Biol. 346:859-873(2005) [PubMed: 15713468] [Abstract]
Cited for: X-RAY SCATTERING SOLUTION STRUCTURE OF C3D IN COMPLEX WITH CR2.
[24]"Structures of complement component C3 provide insights into the function and evolution of immunity."
Janssen B.J.C., Huizinga E.G., Raaijmakers H.C.A., Roos A., Daha M.R., Nilsson-Ekdahl K., Nilsson B., Gros P.
Nature 437:505-511(2005) [PubMed: 16177781] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF C3C, X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF C3.
[25]"Structure of C3b reveals conformational changes that underlie complement activity."
Janssen B.J.C., Christodoulidou A., McCarthy A., Lambris J.D., Gros P.
Nature 444:213-216(2006) [PubMed: 17051160] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF C3B.
[26]"Structure of C3b in complex with CRIg gives insights into regulation of complement activation."
Wiesmann C., Katschke K.J., Yin J., Helmy K.Y., Steffek M., Fairbrother W.J., McCallum S.A., Embuscado L., DeForge L., Hass P.E., van Lookeren Campagne M.
Nature 444:217-220(2006) [PubMed: 17051150] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF C3C IN COMPLEX WITH VSIG4, X-RAY CRYSTALLOGRAPHY (4.1 ANGSTROMS) OF C3B IN COMPLEX WITH VSIG4, GLYCOSYLATION AT ASN-85 AND ASN-939.
[27]"Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition."
Janssen B.J., Halff E.F., Lambris J.D., Gros P.
J. Biol. Chem. 282:29241-29247(2007) [PubMed: 17684013] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 23-936 AND 1321-1663 IN COMPLEX WITH INHIBITOR COMPSTATIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-85.
[28]"A structural basis for complement inhibition by Staphylococcus aureus."
Hammel M., Sfyroera G., Ricklin D., Magotti P., Lambris J.D., Geisbrecht B.V.
Nat. Immunol. 8:430-437(2007) [PubMed: 17351618] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 996-1287 IN COMPLEX WITH S.AUREUS FIB.
[29]"A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d."
Clark E.A., Crennell S., Upadhyay A., Zozulya A.V., Mackay J.D., Svergun D.I., Bagby S., van den Elsen J.M.
Mol. Immunol. 48:452-462(2011) [PubMed: 21055811] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 996-1303 IN COMPLEX WITH S.AUREUS SBI, SUBUNIT.
[30]"A crystal structure of the complex between human complement receptor 2 and its ligand C3d."
van den Elsen J.M., Isenman D.E.
Science 332:608-611(2011) [PubMed: 21527715] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 996-1303 IN COMPLEX WITH CR2, INTERACTION WITH CR2.
[31]"The difference between human C3F and C3S results from a single amino acid change from an asparagine to an aspartate residue at position 1216 on the alpha-chain of the complement component, C3."
Poznansky M.C., Clissold P.M., Lachmann P.J.
J. Immunol. 143:1254-1258(1989) [PubMed: 2473125] [Abstract]
Cited for: VARIANT C3S ASN-1216.
[32]Erratum
Poznansky M.C., Clissold P.M., Lachmann P.J.
J. Immunol. 143:3860-3862(1989) [PubMed: 2584723] [Abstract]
Cited for: RETRACTION.
[33]"Molecular basis of polymorphisms of human complement component C3."
Botto M., Yong Fong K., So A.K., Koch C., Walport M.J.
J. Exp. Med. 172:1011-1017(1990) [PubMed: 1976733] [Abstract]
Cited for: VARIANTS GLY-102 AND LEU-314.
[34]"Inherited human complement C3 deficiency. An amino acid substitution in the beta-chain (Asp549 to Asn) impairs C3 secretion."
Singer L., Whitehead W.T., Akama H., Katz Y., Fishelson Z., Wetsel R.A.
J. Biol. Chem. 269:28494-28499(1994) [PubMed: 7961791] [Abstract]
Cited for: VARIANT C3D ASN-549.
[35]"A novel C3 allotype C3'F02'has an amino acid substitution that may inhibit iC3b synthesis and cause C3-hypocomplementemia."
Watanabe Y., Matsui N., Yan K., Nishimukai H., Tokunaga K., Juji T., Kobayashi N., Kohsaka T.
Mol. Immunol. 30:62-62(1993)
Cited for: VARIANT C3D GLN-1320.
[36]"Complement C3 variant and the risk of age-related macular degeneration."
Yates J.R.W., Sepp T., Matharu B.K., Khan J.C., Thurlby D.A., Shahid H., Clayton D.G., Hayward C., Morgan J., Wright A.F., Armbrecht A.M., Dhillon B., Deary I.J., Redmond E., Bird A.C., Moore A.T.
N. Engl. J. Med. 357:553-561(2007) [PubMed: 17634448] [Abstract]
Cited for: ASSOCIATION OF VARIANT GLY-102 WITH ARMD9.
[37]"Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome."
Fremeaux-Bacchi V., Miller E.C., Liszewski M.K., Strain L., Blouin J., Brown A.L., Moghal N., Kaplan B.S., Weiss R.A., Lhotta K., Kapur G., Mattoo T., Nivet H., Wong W., Gie S., Hurault de Ligny B., Fischbach M., Gupta R. expand/collapse author list , Hauhart R., Meunier V., Loirat C., Dragon-Durey M.A., Fridman W.H., Janssen B.J., Goodship T.H., Atkinson J.P.
Blood 112:4948-4952(2008) [PubMed: 18796626] [Abstract]
Cited for: VARIANTS AHUS5 GLN-592; TRP-592; TRP-735; VAL-1094; ASN-1115; TRP-1158; LYS-1161 AND ASP-1464, CHARACTERIZATION OF VARIANTS AHUS5 GLN-592; TRP-592; VAL-1094; ASN-1115 AND LYS-1161.
[38]"Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome."
Maga T.K., Nishimura C.J., Weaver A.E., Frees K.L., Smith R.J.H.
Hum. Mutat. 31:E1445-E1460(2010) [PubMed: 20513133] [Abstract]
Cited for: VARIANTS AHUS5 VAL-603 AND LEU-1042.
+Additional computationally mapped references.

Web resources

C3base

C3 mutation db

GeneReviews
Wikipedia

Complement C3 entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		K02765 mRNA. Translation: AAA85332.1.
AY513239 Genomic DNA. Translation: AAR89906.1.
CH471139 Genomic DNA. Translation: EAW69071.1.
BC150179 mRNA. Translation: AAI50180.1.
BC150200 mRNA. Translation: AAI50201.1.
IPIIPI00783987.
PIRC3HU. A94065.
RefSeqNP_000055.2. NM_000064.2.
UniGeneHs.529053.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C3DX-ray1.80A996-1287[»]
1GHQX-ray2.04A996-1300[»]
1W2SX-ray-A996-1299[»]
2A73X-ray3.30A23-665[»]
B673-1663[»]
2A74X-ray2.40A/D23-665[»]
B/E749-936[»]
C/F1321-1663[»]
2GOXX-ray2.20A/C996-1287[»]
2HR0X-ray2.26A23-667[»]
B749-1663[»]
2I07X-ray4.00A23-667[»]
B749-1663[»]
2ICEX-ray3.10A/D23-664[»]
B/E749-954[»]
C/F1321-1663[»]
2ICFX-ray4.10A23-664[»]
B749-1663[»]
2NOJX-ray2.70A/C/E/G996-1287[»]
2QKIX-ray2.40A/D23-665[»]
B/E749-936[»]
C/F1321-1663[»]
2WIIX-ray2.70A23-667[»]
B749-1663[»]
2WINX-ray3.90A/C/E/G23-667[»]
B/D/F/H749-1663[»]
2WY7X-ray1.70A996-1303[»]
2WY8X-ray1.70A996-1303[»]
2XQWX-ray2.31A/B996-1287[»]
2XWBX-ray3.49A/C23-664[»]
B/D752-1663[»]
2XWJX-ray4.00A/C/E/G23-667[»]
B/D/F/H749-1663[»]
3D5RX-ray2.10A/B996-1287[»]
3D5SX-ray2.30A/B996-1287[»]
3G6JX-ray3.10A/C23-666[»]
B/D749-1663[»]
3L3OX-ray3.40A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
3L5NX-ray7.54A23-667[»]
B749-1663[»]
3NMSX-ray4.10A23-667[»]
B749-954[»]
C1321-1663[»]
3OEDX-ray3.16A/B996-1303[»]
3OHXX-ray3.50A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
3OXUX-ray2.10A/B/C996-1303[»]
3T4AX-ray3.40A/D23-667[»]
B/E749-954[»]
C/F1321-1663[»]
ProteinModelPortalP01024.
SMRP01024. Positions 23-664, 673-1663.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-35180N.
IntActP01024. 5 interactions.
STRINGP01024.

Protein family/group databases

MEROPSI39.950.

PTM databases

GlycoSuiteDBP01024.
PhosphoSiteP01024.

Polymorphism databases

DMDM119370332.

2D gel databases

SWISS-2DPAGEP01024.
Cornea-2DPAGEP01024.
DOSAC-COBS-2DPAGEP01024.
Siena-2DPAGEP01024.

Proteomic databases

PeptideAtlasP01024.
PRIDEP01024.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245907; ENSP00000245907; ENSG00000125730.
GeneID718.
KEGGhsa:718.
UCSCuc002mfm.1. human.

Organism-specific databases

CTD718.
GeneCardsGC19M006628.
H-InvDBHIX0020036.
HGNCHGNC:1318. C3.
HPACAB004209.
HPA003563.
HPA020432.
MIM120700. gene.
611378. phenotype.
612925. phenotype.
613779. phenotype.
neXtProtNX_P01024.
Orphanet279. Age-related macular degeneration.
93575. Atypical hemolytic uremic syndrome with C3 anomaly.
PharmGKBPA25897.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14935.
HOGENOMHBG755386.
HOVERGENHBG005110.
InParanoidP01024.
OMAVTVHDFP.
OrthoDBEOG41G337.
PhylomeDBP01024.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP01024.
BgeeP01024.
CleanExHS_C3.
GenevestigatorP01024.
GermOnlineENSG00000125730. Homo sapiens.

Family and domain databases

InterProIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR000020. Anaphylatoxin/fibulin.
IPR018081. Anaphylatoxin_.
IPR001840. Anaphylatoxn.
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]
Gene3DG3DSA:2.60.40.690. A-macroglobulin_rcpt-bd. 1 hit.
G3DSA:1.20.91.20. Anaphylatoxin. 1 hit.
KOK03990.
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]
SUPFAMSSF49410. AM_receptor_bind. 1 hit.
SSF47686. Anaphylatoxin. 1 hit.
SSF48239. Terp_cyc_toroid. 1 hit.
SSF50242. TIMP_like. 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

NextBio2922.
PMAP-CutDBP01024.
SOURCESearch...

Entry information

Entry nameCO3_HUMAN
AccessionPrimary (citable) accession number: P01024
Secondary accession number(s): A7E236
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 12, 2006
Last modified: January 25, 2012
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Recent format changes

Overview of recent format changes

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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