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P01024

- CO3_HUMAN

UniProt

P01024 - CO3_HUMAN

Protein

Complement C3

Gene

C3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 187 (01 Oct 2014)
      Sequence version 2 (12 Dec 2006)
      Previous versions | rss
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    Functioni

    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. In chronic inflammation, acts as a chemoattractant for neutrophils By similarity. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.By similarity
    C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.By similarity
    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 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).7 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei747 – 7482Cleavage; by carboxypeptidases
    Sitei748 – 7492Cleavage; by C3 convertase
    Sitei954 – 9552Cleavage; by factor ISequence Analysis
    Sitei1303 – 13042Cleavage; by factor I
    Sitei1320 – 13212Cleavage; by factor I

    GO - Molecular functioni

    1. C5L2 anaphylatoxin chemotactic receptor binding Source: UniProtKB
    2. endopeptidase inhibitor activity Source: InterPro
    3. protein binding Source: IntAct
    4. receptor binding Source: ProtInc

    GO - Biological processi

    1. complement activation Source: BHF-UCL
    2. complement activation, alternative pathway Source: Reactome
    3. complement activation, classical pathway Source: UniProtKB-KW
    4. fatty acid metabolic process Source: UniProtKB-KW
    5. G-protein coupled receptor signaling pathway Source: ProtInc
    6. immune response Source: ProtInc
    7. inflammatory response Source: UniProtKB-KW
    8. innate immune response Source: Reactome
    9. positive regulation of activation of membrane attack complex Source: Ensembl
    10. positive regulation of angiogenesis Source: Ensembl
    11. positive regulation of apoptotic cell clearance Source: BHF-UCL
    12. positive regulation of glucose transport Source: UniProtKB
    13. positive regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
    14. positive regulation of lipid storage Source: UniProtKB
    15. positive regulation of protein phosphorylation Source: UniProtKB
    16. positive regulation of type IIa hypersensitivity Source: Ensembl
    17. positive regulation vascular endothelial growth factor production Source: BHF-UCL
    18. regulation of complement activation Source: Reactome
    19. regulation of immune response Source: Reactome
    20. regulation of triglyceride biosynthetic process Source: UniProtKB
    21. signal transduction Source: ProtInc

    Keywords - Biological processi

    Complement alternate pathway, Complement pathway, Fatty acid metabolism, Immunity, Inflammatory response, Innate immunity, Lipid metabolism

    Enzyme and pathway databases

    ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
    REACT_118707. Regulation of Complement cascade.
    REACT_14819. Peptide ligand-binding receptors.
    REACT_19231. G alpha (i) signalling events.
    REACT_7972. Activation of C3 and C5.
    REACT_8001. Alternative complement activation.

    Protein family/group databases

    MEROPSiI39.950.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Complement C3
    Alternative name(s):
    C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1
    Cleaved into the following 12 chains:
    Gene namesi
    Name:C3
    Synonyms:CPAMD1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:1318. C3.

    Subcellular locationi

    GO - Cellular componenti

    1. blood microparticle Source: UniProt
    2. extracellular region Source: Reactome
    3. extracellular space Source: UniProt
    4. extracellular vesicular exosome Source: UniProtKB
    5. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti549 – 5491D → N in C3D; impairs secretion; variant confirmed at protein level. 2 Publications
    VAR_001985
    Natural varianti1320 – 13201R → Q in C3D; allotype C3'F02'; may inhibit IC3B synthesis. 1 Publication
    VAR_001986
    Macular degeneration, age-related, 9 (ARMD9) [MIM:611378]: A form of age-related macular degeneration, 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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti102 – 1021R → G in allele C3F; associated with susceptibility to ARMD9; results in decreased binding affinity for regulator factor H; results in reduced sensitivity to cleavage by factor I. 2 Publications
    Corresponds to variant rs2230199 [ dbSNP | Ensembl ].
    VAR_001983
    Natural varianti155 – 1551K → Q in ARMD9; results in resistance to proteolytic inactivation by CFH and CFI. 1 Publication
    VAR_070941
    Hemolytic uremic syndrome atypical 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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti592 – 5921R → Q in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063213
    Natural varianti592 – 5921R → W in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063214
    Natural varianti603 – 6031F → V in AHUS5. 1 Publication
    VAR_063654
    Natural varianti735 – 7351R → W in AHUS5. 1 Publication
    Corresponds to variant rs117793540 [ dbSNP | Ensembl ].
    VAR_063215
    Natural varianti1042 – 10421R → L in AHUS5. 1 Publication
    VAR_063655
    Natural varianti1094 – 10941A → V in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063216
    Natural varianti1115 – 11151D → N in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063217
    Natural varianti1158 – 11581C → W in AHUS5. 1 Publication
    VAR_063218
    Natural varianti1161 – 11611Q → K in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063219
    Natural varianti1464 – 14641H → D in AHUS5. 1 Publication
    VAR_063220
    Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1029 – 10291D → A: Minor effect on binding of C3d to CR2. 3 Publications
    Mutagenesisi1030 – 10301E → A: Impaired binding of C3d to CR2. 3 Publications
    Mutagenesisi1032 – 10321E → A: Impaired binding of C3d to CR2. 3 Publications
    Mutagenesisi1035 – 10351E → A: No effect on binding of C3d to CR2. 2 Publications
    Mutagenesisi1042 – 10421R → M: Impaired binding of C3d to CR2. 2 Publications
    Mutagenesisi1108 – 11092IL → RR: Impaired binding of C3d to CR2; when associated with A-1163. 1 Publication
    Mutagenesisi1110 – 11101E → A: No effect on binding of C3d to CR2. 2 Publications
    Mutagenesisi1115 – 11151D → A: No effect on binding of C3d to CR2. 2 Publications
    Mutagenesisi1121 – 11211D → A: No effect on binding of C3d to CR2. 2 Publications
    Mutagenesisi1140 – 11401D → A: No effect on binding of C3d to CR2. 3 Publications
    Mutagenesisi1153 – 11531E → A: Impaired binding of C3d to CR2. 3 Publications
    Mutagenesisi1156 – 11561D → A: Impaired binding of C3d to CR2. 3 Publications
    Mutagenesisi1159 – 11591E → A: Impaired binding of C3d to CR2. 3 Publications
    Mutagenesisi1160 – 11601E → A: Minor effect on binding of C3d to CR2. 3 Publications
    Mutagenesisi1163 – 11631N → A: No effect on binding of C3d to CR2. Impaired binding of C3d to CR2; when associated with 1108-R-R-1109. 4 Publications
    Mutagenesisi1163 – 11631N → R: Impaired binding of C3d to CR2. 4 Publications
    Mutagenesisi1284 – 12841K → A: Impaired binding of C3d to CR2. 2 Publications

    Keywords - Diseasei

    Age-related macular degeneration, Disease mutation, Hemolytic uremic syndrome

    Organism-specific databases

    MIMi611378. phenotype.
    612925. phenotype.
    613779. phenotype.
    Orphaneti279. Age-related macular degeneration.
    93575. Atypical hemolytic uremic syndrome with C3 anomaly.
    280133. Complement component 3 deficiency.
    PharmGKBiPA25897.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 22221 PublicationAdd
    BLAST
    Chaini23 – 16631641Complement C3PRO_0000005907Add
    BLAST
    Chaini23 – 667645Complement C3 beta chainPRO_0000005908Add
    BLAST
    Chaini569 – 66799C3-beta-cBy similarityPRO_0000430430Add
    BLAST
    Chaini672 – 1663992Complement C3 alpha chainPRO_0000005909Add
    BLAST
    Chaini672 – 74877C3a anaphylatoxinPRO_0000005910Add
    BLAST
    Chaini672 – 74776Acylation stimulating proteinPRO_0000419935Add
    BLAST
    Chaini749 – 1663915Complement C3b alpha' chainPRO_0000005911Add
    BLAST
    Chaini749 – 954206Complement C3c alpha' chain fragment 1PRO_0000005912Add
    BLAST
    Chaini955 – 1303349Complement C3dg fragmentPRO_0000005913Add
    BLAST
    Chaini955 – 100147Complement C3g fragmentPRO_0000005914Add
    BLAST
    Chaini1002 – 1303302Complement C3d fragmentPRO_0000005915Add
    BLAST
    Peptidei1304 – 132017Complement C3f fragment1 PublicationPRO_0000005916Add
    BLAST
    Chaini1321 – 1663343Complement C3c alpha' chain fragment 2PRO_0000273948Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi85 – 851N-linked (GlcNAc...)7 Publications
    Disulfide bondi559 ↔ 816Interchain (between beta and alpha chains)
    Disulfide bondi627 ↔ 662
    Disulfide bondi693 ↔ 7201 Publication
    Disulfide bondi694 ↔ 727
    Disulfide bondi707 ↔ 728
    Disulfide bondi873 ↔ 1513
    Glycosylationi939 – 9391N-linked (GlcNAc...)3 Publications
    Cross-linki1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)
    Disulfide bondi1101 ↔ 1158
    Disulfide bondi1358 ↔ 1489
    Disulfide bondi1389 ↔ 1458
    Disulfide bondi1506 ↔ 1511
    Disulfide bondi1518 ↔ 1590
    Disulfide bondi1537 ↔ 1661
    Glycosylationi1617 – 16171N-linked (GlcNAc...)1 Publication
    Disulfide bondi1637 ↔ 1646

    Post-translational modificationi

    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 insulin and dietary chylomicrons.
    Phosphorylation sites are present in the extracellular medium.

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Thioester bond

    Proteomic databases

    MaxQBiP01024.
    PaxDbiP01024.
    PeptideAtlasiP01024.
    PRIDEiP01024.

    2D gel databases

    DOSAC-COBS-2DPAGEP01024.
    SWISS-2DPAGEP01024.

    PTM databases

    PhosphoSiteiP01024.
    UniCarbKBiP01024.

    Miscellaneous databases

    PMAP-CutDBP01024.

    Expressioni

    Tissue specificityi

    Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods.2 Publications

    Gene expression databases

    ArrayExpressiP01024.
    BgeeiP01024.
    CleanExiHS_C3.
    GenevestigatoriP01024.

    Organism-specific databases

    HPAiCAB004209.
    HPA003563.
    HPA020432.

    Interactioni

    Subunit structurei

    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. 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 GRP77.12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CFHP086032EBI-6863145,EBI-1223708
    VSIG4Q9Y279-15EBI-905851,EBI-903144
    VSIG4Q9Y279-22EBI-905851,EBI-903148

    Protein-protein interaction databases

    BioGridi107179. 14 interactions.
    DIPiDIP-35180N.
    IntActiP01024. 10 interactions.
    MINTiMINT-5003988.
    STRINGi9606.ENSP00000245907.

    Structurei

    Secondary structure

    1
    1663
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi28 – 358
    Beta strandi36 – 416
    Beta strandi43 – 475
    Beta strandi54 – 563
    Beta strandi59 – 613
    Turni62 – 643
    Beta strandi67 – 693
    Beta strandi73 – 753
    Helixi78 – 803
    Beta strandi87 – 893
    Helixi94 – 974
    Beta strandi105 – 1128
    Beta strandi115 – 12410
    Beta strandi129 – 1357
    Beta strandi137 – 1393
    Beta strandi143 – 15210
    Beta strandi162 – 1687
    Beta strandi174 – 1818
    Turni183 – 1875
    Beta strandi188 – 1947
    Beta strandi202 – 2109
    Beta strandi216 – 2238
    Beta strandi233 – 24412
    Beta strandi251 – 2588
    Beta strandi267 – 27711
    Beta strandi280 – 2834
    Helixi285 – 2873
    Beta strandi289 – 2946
    Beta strandi297 – 3026
    Helixi304 – 3085
    Turni310 – 3123
    Helixi316 – 3194
    Beta strandi323 – 33614
    Beta strandi338 – 35013
    Beta strandi354 – 3563
    Beta strandi358 – 3603
    Beta strandi362 – 3643
    Beta strandi368 – 37710
    Beta strandi379 – 3835
    Beta strandi389 – 3946
    Helixi395 – 3973
    Beta strandi398 – 4003
    Beta strandi405 – 4128
    Beta strandi420 – 4267
    Turni429 – 4313
    Turni433 – 4353
    Beta strandi438 – 4447
    Helixi449 – 4513
    Beta strandi455 – 4606
    Beta strandi469 – 47810
    Turni481 – 4833
    Turni484 – 4863
    Beta strandi489 – 4968
    Beta strandi499 – 5079
    Beta strandi513 – 5208
    Helixi523 – 5253
    Beta strandi527 – 53812
    Beta strandi540 – 55415
    Beta strandi564 – 5674
    Turni568 – 5703
    Beta strandi571 – 5733
    Beta strandi580 – 5889
    Beta strandi592 – 5987
    Helixi600 – 6034
    Helixi613 – 6219
    Beta strandi628 – 6303
    Beta strandi633 – 6364
    Helixi637 – 6404
    Turni641 – 6433
    Beta strandi644 – 6474
    Beta strandi649 – 6513
    Helixi675 – 68410
    Helixi688 – 69710
    Helixi707 – 7104
    Turni712 – 7143
    Helixi718 – 74326
    Beta strandi753 – 7553
    Helixi758 – 7603
    Beta strandi769 – 7713
    Beta strandi775 – 7773
    Beta strandi786 – 7949
    Beta strandi800 – 81011
    Turni811 – 8133
    Beta strandi814 – 8174
    Beta strandi821 – 8255
    Beta strandi828 – 8347
    Beta strandi837 – 8404
    Beta strandi845 – 8539
    Beta strandi860 – 8667
    Beta strandi872 – 8754
    Beta strandi878 – 8803
    Beta strandi882 – 8887
    Beta strandi892 – 90211
    Beta strandi906 – 91914
    Beta strandi922 – 93211
    Helixi942 – 9476
    Helixi949 – 9524
    Beta strandi956 – 9627
    Beta strandi968 – 9703
    Beta strandi983 – 9886
    Helixi989 – 9957
    Helixi997 – 9993
    Helixi1001 – 10033
    Beta strandi1009 – 10124
    Helixi1013 – 103119
    Helixi1034 – 10374
    Helixi1041 – 105717
    Turni1062 – 10643
    Beta strandi1067 – 10726
    Helixi1076 – 108914
    Turni1090 – 10923
    Helixi1097 – 111115
    Turni1114 – 11163
    Helixi1127 – 11337
    Helixi1139 – 115820
    Turni1159 – 11613
    Helixi1165 – 117915
    Helixi1180 – 11823
    Helixi1186 – 119813
    Helixi1204 – 121310
    Turni1216 – 12183
    Beta strandi1223 – 12253
    Helixi1226 – 124318
    Turni1246 – 12483
    Helixi1249 – 125810
    Beta strandi1262 – 12654
    Helixi1269 – 128517
    Beta strandi1293 – 12997
    Beta strandi1303 – 13053
    Beta strandi1307 – 13126
    Beta strandi1313 – 13164
    Beta strandi1320 – 13267
    Beta strandi1331 – 13333
    Beta strandi1337 – 13393
    Beta strandi1340 – 135011
    Beta strandi1359 – 136911
    Beta strandi1381 – 139212
    Beta strandi1394 – 13963
    Beta strandi1400 – 14067
    Beta strandi1409 – 14135
    Helixi1415 – 14239
    Beta strandi1424 – 14263
    Beta strandi1430 – 14323
    Turni1438 – 14403
    Beta strandi1443 – 14497
    Beta strandi1453 – 14553
    Beta strandi1459 – 14679
    Beta strandi1469 – 14713
    Beta strandi1475 – 14817
    Beta strandi1484 – 149310
    Turni1495 – 14984
    Beta strandi1504 – 15074
    Beta strandi1510 – 15134
    Turni1515 – 15173
    Beta strandi1518 – 15203
    Turni1524 – 15263
    Helixi1529 – 15357
    Beta strandi1537 – 15404
    Beta strandi1541 – 155414
    Beta strandi1556 – 157015
    Beta strandi1581 – 15877
    Helixi1588 – 15903
    Helixi1591 – 15944
    Beta strandi1601 – 16077
    Helixi1608 – 16103
    Beta strandi1611 – 16133
    Beta strandi1615 – 16173
    Beta strandi1619 – 16213
    Beta strandi1627 – 16315
    Helixi1634 – 16363
    Beta strandi1637 – 16393
    Turni1640 – 16423
    Helixi1643 – 165715

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    3RJ3X-ray2.35A/B/C996-1303[»]
    3T4AX-ray3.40A/D23-667[»]
    B/E749-954[»]
    C/F1321-1663[»]
    4HW5X-ray2.25A/B672-748[»]
    4HWJX-ray2.60A672-747[»]
    4I6OX-ray2.14A672-748[»]
    4M76X-ray2.80A994-1288[»]
    ProteinModelPortaliP01024.
    SMRiP01024. Positions 23-664, 673-1663.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP01024.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini693 – 72836Anaphylatoxin-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini1518 – 1661144NTRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1424 – 145633Properdin-bindingAdd
    BLAST

    Sequence similaritiesi

    Contains 1 anaphylatoxin-like domain.PROSITE-ProRule annotation
    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG241555.
    HOGENOMiHOG000286028.
    HOVERGENiHBG005110.
    InParanoidiP01024.
    KOiK03990.
    OMAiPGMPFDL.
    OrthoDBiEOG77HDCX.
    PhylomeDBiP01024.
    TreeFamiTF313285.

    Family and domain databases

    Gene3Di1.20.91.20. 1 hit.
    1.50.10.20. 1 hit.
    2.60.40.690. 1 hit.
    InterProiIPR009048. 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]
    PfamiPF00207. 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]
    PRINTSiPR00004. ANAPHYLATOXN.
    SMARTiSM00104. ANATO. 1 hit.
    SM00643. C345C. 1 hit.
    [Graphical view]
    SUPFAMiSSF47686. SSF47686. 1 hit.
    SSF48239. SSF48239. 1 hit.
    SSF49410. SSF49410. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
    PS01177. ANAPHYLATOXIN_1. 1 hit.
    PS01178. ANAPHYLATOXIN_2. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P01024-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGPTSGPSLL LLLLTHLPLA LGSPMYSIIT PNILRLESEE TMVLEAHDAQ     50
    GDVPVTVTVH DFPGKKLVLS SEKTVLTPAT NHMGNVTFTI PANREFKSEK 100
    GRNKFVTVQA TFGTQVVEKV VLVSLQSGYL FIQTDKTIYT PGSTVLYRIF 150
    TVNHKLLPVG RTVMVNIENP EGIPVKQDSL SSQNQLGVLP LSWDIPELVN 200
    MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE KFYYIYNEKG 250
    LEVTITARFL YGKKVEGTAF VIFGIQDGEQ RISLPESLKR IPIEDGSGEV 300
    VLSRKVLLDG VQNPRAEDLV GKSLYVSATV ILHSGSDMVQ AERSGIPIVT 350
    SPYQIHFTKT PKYFKPGMPF DLMVFVTNPD GSPAYRVPVA VQGEDTVQSL 400
    TQGDGVAKLS INTHPSQKPL SITVRTKKQE LSEAEQATRT MQALPYSTVG 450
    NSNNYLHLSV LRTELRPGET LNVNFLLRMD RAHEAKIRYY TYLIMNKGRL 500
    LKAGRQVREP GQDLVVLPLS ITTDFIPSFR LVAYYTLIGA SGQREVVADS 550
    VWVDVKDSCV GSLVVKSGQS EDRQPVPGQQ MTLKIEGDHG ARVVLVAVDK 600
    GVFVLNKKNK LTQSKIWDVV EKADIGCTPG SGKDYAGVFS DAGLTFTSSS 650
    GQQTAQRAEL QCPQPAARRR RSVQLTEKRM DKVGKYPKEL RKCCEDGMRE 700
    NPMRFSCQRR TRFISLGEAC KKVFLDCCNY ITELRRQHAR ASHLGLARSN 750
    LDEDIIAEEN IVSRSEFPES WLWNVEDLKE PPKNGISTKL MNIFLKDSIT 800
    TWEILAVSMS DKKGICVADP FEVTVMQDFF IDLRLPYSVV RNEQVEIRAV 850
    LYNYRQNQEL KVRVELLHNP AFCSLATTKR RHQQTVTIPP KSSLSVPYVI 900
    VPLKTGLQEV EVKAAVYHHF ISDGVRKSLK VVPEGIRMNK TVAVRTLDPE 950
    RLGREGVQKE DIPPADLSDQ VPDTESETRI LLQGTPVAQM TEDAVDAERL 1000
    KHLIVTPSGC GEQNMIGMTP TVIAVHYLDE TEQWEKFGLE KRQGALELIK 1050
    KGYTQQLAFR QPSSAFAAFV KRAPSTWLTA YVVKVFSLAV NLIAIDSQVL 1100
    CGAVKWLILE KQKPDGVFQE DAPVIHQEMI GGLRNNNEKD MALTAFVLIS 1150
    LQEAKDICEE QVNSLPGSIT KAGDFLEANY MNLQRSYTVA IAGYALAQMG 1200
    RLKGPLLNKF LTTAKDKNRW EDPGKQLYNV EATSYALLAL LQLKDFDFVP 1250
    PVVRWLNEQR YYGGGYGSTQ ATFMVFQALA QYQKDAPDHQ ELNLDVSLQL 1300
    PSRSSKITHR IHWESASLLR SEETKENEGF TVTAEGKGQG TLSVVTMYHA 1350
    KAKDQLTCNK FDLKVTIKPA PETEKRPQDA KNTMILEICT RYRGDQDATM 1400
    SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD RNTLIIYLDK 1450
    VSHSEDDCLA FKVHQYFNVE LIQPGAVKVY AYYNLEESCT RFYHPEKEDG 1500
    KLNKLCRDEL CRCAEENCFI QKSDDKVTLE ERLDKACEPG VDYVYKTRLV 1550
    KVQLSNDFDE YIMAIEQTIK SGSDEVQVGQ QRTFISPIKC REALKLEEKK 1600
    HYLMWGLSSD FWGEKPNLSY IIGKDTWVEH WPEEDECQDE ENQKQCQDLG 1650
    AFTESMVVFG CPN 1663
    Length:1,663
    Mass (Da):187,148
    Last modified:December 12, 2006 - v2
    Checksum:i30C2832A9E75FFC4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti681 – 6811D → N AA sequence (PubMed:1238393)Curated
    Sequence conflicti700 – 7001E → Q AA sequence (PubMed:1238393)Curated
    Sequence conflicti1026 – 10261H → S AA sequence (PubMed:6175959)Curated

    Polymorphismi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti102 – 1021R → G in allele C3F; associated with susceptibility to ARMD9; results in decreased binding affinity for regulator factor H; results in reduced sensitivity to cleavage by factor I. 2 Publications
    Corresponds to variant rs2230199 [ dbSNP | Ensembl ].
    VAR_001983
    Natural varianti155 – 1551K → Q in ARMD9; results in resistance to proteolytic inactivation by CFH and CFI. 1 Publication
    VAR_070941
    Natural varianti314 – 3141P → L.3 Publications
    Corresponds to variant rs1047286 [ dbSNP | Ensembl ].
    VAR_001984
    Natural varianti469 – 4691E → D.
    Corresponds to variant rs11569422 [ dbSNP | Ensembl ].
    VAR_020262
    Natural varianti549 – 5491D → N in C3D; impairs secretion; variant confirmed at protein level. 2 Publications
    VAR_001985
    Natural varianti592 – 5921R → Q in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063213
    Natural varianti592 – 5921R → W in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063214
    Natural varianti603 – 6031F → V in AHUS5. 1 Publication
    VAR_063654
    Natural varianti735 – 7351R → W in AHUS5. 1 Publication
    Corresponds to variant rs117793540 [ dbSNP | Ensembl ].
    VAR_063215
    Natural varianti863 – 8631R → K.1 Publication
    Corresponds to variant rs11569472 [ dbSNP | Ensembl ].
    VAR_019206
    Natural varianti1042 – 10421R → L in AHUS5. 1 Publication
    VAR_063655
    Natural varianti1094 – 10941A → V in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063216
    Natural varianti1115 – 11151D → N in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063217
    Natural varianti1158 – 11581C → W in AHUS5. 1 Publication
    VAR_063218
    Natural varianti1161 – 11611Q → K in AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I. 1 Publication
    VAR_063219
    Natural varianti1216 – 12161D → N in C3S. 1 Publication
    VAR_022761
    Natural varianti1224 – 12241G → D.1 Publication
    Corresponds to variant rs11569534 [ dbSNP | Ensembl ].
    VAR_019207
    Natural varianti1320 – 13201R → Q in C3D; allotype C3'F02'; may inhibit IC3B synthesis. 1 Publication
    VAR_001986
    Natural varianti1367 – 13671I → T.1 Publication
    Corresponds to variant rs11569541 [ dbSNP | Ensembl ].
    VAR_019208
    Natural varianti1464 – 14641H → D in AHUS5. 1 Publication
    VAR_063220
    Natural varianti1521 – 15211Q → R.
    Corresponds to variant rs7256789 [ dbSNP | Ensembl ].
    VAR_029792
    Natural varianti1601 – 16011H → N.
    Corresponds to variant rs1803225 [ dbSNP | Ensembl ].
    VAR_029793
    Natural varianti1619 – 16191S → R.
    Corresponds to variant rs2230210 [ dbSNP | Ensembl ].
    VAR_029326

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS32883.1.
    PIRiA94065. C3HU.
    RefSeqiNP_000055.2. NM_000064.2.
    UniGeneiHs.529053.

    Genome annotation databases

    EnsembliENST00000245907; ENSP00000245907; ENSG00000125730.
    GeneIDi718.
    KEGGihsa:718.
    UCSCiuc002mfm.3. human.

    Polymorphism databases

    DMDMi119370332.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    C3base

    C3 mutation db

    Wikipedia

    Complement C3 entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS32883.1.
    PIRi A94065. C3HU.
    RefSeqi NP_000055.2. NM_000064.2.
    UniGenei Hs.529053.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1C3D X-ray 1.80 A 996-1287 [» ]
    1GHQ X-ray 2.04 A 996-1300 [» ]
    1W2S X-ray - A 996-1299 [» ]
    2A73 X-ray 3.30 A 23-665 [» ]
    B 673-1663 [» ]
    2A74 X-ray 2.40 A/D 23-665 [» ]
    B/E 749-936 [» ]
    C/F 1321-1663 [» ]
    2GOX X-ray 2.20 A/C 996-1287 [» ]
    2HR0 X-ray 2.26 A 23-667 [» ]
    B 749-1663 [» ]
    2I07 X-ray 4.00 A 23-667 [» ]
    B 749-1663 [» ]
    2ICE X-ray 3.10 A/D 23-664 [» ]
    B/E 749-954 [» ]
    C/F 1321-1663 [» ]
    2ICF X-ray 4.10 A 23-664 [» ]
    B 749-1663 [» ]
    2NOJ X-ray 2.70 A/C/E/G 996-1287 [» ]
    2QKI X-ray 2.40 A/D 23-665 [» ]
    B/E 749-936 [» ]
    C/F 1321-1663 [» ]
    2WII X-ray 2.70 A 23-667 [» ]
    B 749-1663 [» ]
    2WIN X-ray 3.90 A/C/E/G 23-667 [» ]
    B/D/F/H 749-1663 [» ]
    2WY7 X-ray 1.70 A 996-1303 [» ]
    2WY8 X-ray 1.70 A 996-1303 [» ]
    2XQW X-ray 2.31 A/B 996-1287 [» ]
    2XWB X-ray 3.49 A/C 23-664 [» ]
    B/D 752-1663 [» ]
    2XWJ X-ray 4.00 A/C/E/G 23-667 [» ]
    B/D/F/H 749-1663 [» ]
    3D5R X-ray 2.10 A/B 996-1287 [» ]
    3D5S X-ray 2.30 A/B 996-1287 [» ]
    3G6J X-ray 3.10 A/C 23-666 [» ]
    B/D 749-1663 [» ]
    3L3O X-ray 3.40 A/D 23-667 [» ]
    B/E 749-954 [» ]
    C/F 1321-1663 [» ]
    3L5N X-ray 7.54 A 23-667 [» ]
    B 749-1663 [» ]
    3NMS X-ray 4.10 A 23-667 [» ]
    B 749-954 [» ]
    C 1321-1663 [» ]
    3OED X-ray 3.16 A/B 996-1303 [» ]
    3OHX X-ray 3.50 A/D 23-667 [» ]
    B/E 749-954 [» ]
    C/F 1321-1663 [» ]
    3OXU X-ray 2.10 A/B/C 996-1303 [» ]
    3RJ3 X-ray 2.35 A/B/C 996-1303 [» ]
    3T4A X-ray 3.40 A/D 23-667 [» ]
    B/E 749-954 [» ]
    C/F 1321-1663 [» ]
    4HW5 X-ray 2.25 A/B 672-748 [» ]
    4HWJ X-ray 2.60 A 672-747 [» ]
    4I6O X-ray 2.14 A 672-748 [» ]
    4M76 X-ray 2.80 A 994-1288 [» ]
    ProteinModelPortali P01024.
    SMRi P01024. Positions 23-664, 673-1663.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107179. 14 interactions.
    DIPi DIP-35180N.
    IntActi P01024. 10 interactions.
    MINTi MINT-5003988.
    STRINGi 9606.ENSP00000245907.

    Chemistry

    BindingDBi P01024.
    ChEMBLi CHEMBL4917.

    Protein family/group databases

    MEROPSi I39.950.

    PTM databases

    PhosphoSitei P01024.
    UniCarbKBi P01024.

    Polymorphism databases

    DMDMi 119370332.

    2D gel databases

    DOSAC-COBS-2DPAGE P01024.
    SWISS-2DPAGE P01024.

    Proteomic databases

    MaxQBi P01024.
    PaxDbi P01024.
    PeptideAtlasi P01024.
    PRIDEi P01024.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000245907 ; ENSP00000245907 ; ENSG00000125730 .
    GeneIDi 718.
    KEGGi hsa:718.
    UCSCi uc002mfm.3. human.

    Organism-specific databases

    CTDi 718.
    GeneCardsi GC19M006677.
    GeneReviewsi C3.
    H-InvDB HIX0020036.
    HGNCi HGNC:1318. C3.
    HPAi CAB004209.
    HPA003563.
    HPA020432.
    MIMi 120700. gene.
    611378. phenotype.
    612925. phenotype.
    613779. phenotype.
    neXtProti NX_P01024.
    Orphaneti 279. Age-related macular degeneration.
    93575. Atypical hemolytic uremic syndrome with C3 anomaly.
    280133. Complement component 3 deficiency.
    PharmGKBi PA25897.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG241555.
    HOGENOMi HOG000286028.
    HOVERGENi HBG005110.
    InParanoidi P01024.
    KOi K03990.
    OMAi PGMPFDL.
    OrthoDBi EOG77HDCX.
    PhylomeDBi P01024.
    TreeFami TF313285.

    Enzyme and pathway databases

    Reactomei REACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
    REACT_118707. Regulation of Complement cascade.
    REACT_14819. Peptide ligand-binding receptors.
    REACT_19231. G alpha (i) signalling events.
    REACT_7972. Activation of C3 and C5.
    REACT_8001. Alternative complement activation.

    Miscellaneous databases

    ChiTaRSi C3. human.
    EvolutionaryTracei P01024.
    GeneWikii Complement_component_3.
    GenomeRNAii 718.
    NextBioi 2922.
    PMAP-CutDB P01024.
    PROi P01024.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P01024.
    Bgeei P01024.
    CleanExi HS_C3.
    Genevestigatori P01024.

    Family and domain databases

    Gene3Di 1.20.91.20. 1 hit.
    1.50.10.20. 1 hit.
    2.60.40.690. 1 hit.
    InterProi IPR009048. 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 ]
    Pfami PF00207. 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 ]
    PRINTSi PR00004. ANAPHYLATOXN.
    SMARTi SM00104. ANATO. 1 hit.
    SM00643. C345C. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47686. SSF47686. 1 hit.
    SSF48239. SSF48239. 1 hit.
    SSF49410. SSF49410. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEi PS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
    PS01177. ANAPHYLATOXIN_1. 1 hit.
    PS01178. ANAPHYLATOXIN_2. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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. 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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis."
      Baldo A., Sniderman A.D., St-Luce S., Avramoglu R.K., Maslowska M., Hoang B., Monge J.C., Bell A., Mulay S., Cianflone K.
      J. Clin. Invest. 92:1543-1547(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF N-TERMINUS, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
    6. "Human anaphylatoxin (C3a) from the third component of complement. Primary structure."
      Hugli T.E.
      J. Biol. Chem. 250:8293-8301(1975) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 672-748.
    7. "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] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 955-966, SUBUNIT.
      Tissue: Serum.
    8. "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] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 988-1036.
    9. "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] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1409-1563.
    10. "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] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HERPES SIMPLEX VIRUS HHV-1 AND HHV-2 GYCOPROTEIN C.
    11. "Purification and characterization of acylation stimulating protein."
      Cianflone K.M., Sniderman A.D., Walsh M.J., Vu H.T., Gagnon J., Rodriguez M.A.
      J. Biol. Chem. 264:426-430(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "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] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THE THIOESTER BOND REGION.
    13. "Disulfide bridges in human complement component C3b."
      Dolmer K., Sottrup-Jensen L.
      FEBS Lett. 315:85-90(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BONDS.
    14. "Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line."
      Tao Y., Cianflone K., Sniderman A.D., Colby-Germinario S.P., Germinario R.J.
      Biochim. Biophys. Acta 1344:221-229(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period."
      Saleh J., Summers L.K., Cianflone K., Fielding B.A., Sniderman A.D., Frayn K.N.
      J. Lipid Res. 39:884-891(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, FUNCTION.
    16. "Acylation-stimulating protein (ASP): structure-function determinants of cell surface binding and triacylglycerol synthetic activity."
      Murray I., Kohl J., Cianflone K.
      Biochem. J. 342:41-48(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. "The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des Arg(74)."
      Cain S.A., Monk P.N.
      J. Biol. Chem. 277:7165-7169(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH C5AR2.
    18. "The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein."
      Kalant D., Cain S.A., Maslowska M., Sniderman A.D., Cianflone K., Monk P.N.
      J. Biol. Chem. 278:11123-11129(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH C5AR2.
    19. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-85.
    20. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-939.
      Tissue: Plasma.
    21. "Acylation-stimulating protein: effect of acute exercise and endurance training."
      Schrauwen P., Hesselink M.K., Jain M., Cianflone K.
      Int. J. Obes. Relat. Metab. Disord. 29:632-638(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: EFFECTS OF EXERCISE.
    22. "C5L2 is a functional receptor for acylation-stimulating protein."
      Kalant D., MacLaren R., Cui W., Samanta R., Monk P.N., Laporte S.A., Cianflone K.
      J. Biol. Chem. 280:23936-23944(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    23. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85; ASN-939 AND ASN-1617.
      Tissue: Plasma.
    24. "Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes."
      Yang Y., Lu H.L., Zhang J., Yu H.Y., Wang H.W., Zhang M.X., Cianflone K.
      Int. J. Obes. Relat. Metab. Disord. 30:439-446(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH TYPE 2 DIABETES.
    25. "Targeting the signaling pathway of acylation stimulating protein."
      Maslowska M., Legakis H., Assadi F., Cianflone K.
      J. Lipid Res. 47:643-652(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
    26. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85.
      Tissue: Platelet.
    27. "Acylation stimulating protein but not complement C3 associates with metabolic syndrome components in Chinese children and adolescents."
      Wamba P.C., Mi J., Zhao X.Y., Zhang M.X., Wen Y., Cheng H., Hou D.Q., Cianflone K.
      Eur. J. Endocrinol. 159:781-790(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH OBESITY.
    28. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85.
      Tissue: Liver.
    29. "C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost in S323I-C5L2 mutation."
      Cui W., Simaan M., Laporte S., Lodge R., Cianflone K.
      Mol. Immunol. 46:3086-3098(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    30. "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] [Europe PMC] [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.
    31. "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] [Europe PMC] [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.
    32. "Serum complement C3: a determinant of cardiometabolic risk, additive to the metabolic syndrome, in middle-aged population."
      Onat A., Hergenc G., Can G., Kaya Z., Yuksel H.
      Metabolism 59:628-634(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH CORONARY HEART DISEASE.
    33. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    34. "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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF C3A.
    35. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D.
    36. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D IN COMPLEX WITH CR2, MUTAGENESIS OF 1108-ILE-LEU-1109 AND ASN-1163.
    37. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY SCATTERING SOLUTION STRUCTURE OF C3D IN COMPLEX WITH CR2.
    38. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF C3C, X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF C3.
    39. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF C3B.
    40. "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] [Europe PMC] [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.
    41. "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] [Europe PMC] [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.
    42. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 996-1287 IN COMPLEX WITH S.AUREUS FIB.
    43. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 996-1303 IN COMPLEX WITH S.AUREUS SBI, SUBUNIT.
    44. "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] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 996-1303 IN COMPLEX WITH CR2, INTERACTION WITH CR2.
    45. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT C3S ASN-1216.
    46. Erratum
      Poznansky M.C., Clissold P.M., Lachmann P.J.
      J. Immunol. 143:3860-3862(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: RETRACTION.
    47. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS GLY-102 AND LEU-314.
    48. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT C3D ASN-549.
    49. "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.
    50. Cited for: ASSOCIATION OF VARIANT GLY-102 WITH ARMD9.
    51. 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.
    52. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHUS5 VAL-603 AND LEU-1042.
    53. "Quantitative detection of single amino acid polymorphisms by targeted proteomics."
      Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X., Zeng R., Wu J.R.
      J. Mol. Cell Biol. 3:309-315(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ASN-549, IDENTIFICATION BY MASS SPECTROMETRY.
    54. "Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk."
      Heurich M., Martinez-Barricarte R., Francis N.J., Roberts D.L., Rodriguez de Cordoba S., Morgan B.P., Harris C.L.
      Proc. Natl. Acad. Sci. U.S.A. 108:8761-8766(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT GLY-102.
    55. Cited for: VARIANT ARMD9 GLN-155, CHARACTERIZATION OF VARIANT ARMD9 GLN-155.

    Entry informationi

    Entry nameiCO3_HUMAN
    AccessioniPrimary (citable) accession number: P01024
    Secondary accession number(s): A7E236
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: December 12, 2006
    Last modified: October 1, 2014
    This is version 187 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Caution

    According to PubMed:21527715, the interaction surface between C3 and CR2 reported in PubMed:11387479 is artifactual and can be ascribed to the presence of zinc acetate in the buffer.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3