Complement component 3

C3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ONT, 1C3D, 1GHQ, 1W2S, 2A73, 2A74, 2GOX, 2I07, 2ICE, 2ICF, 2NOJ, 2QKI, 2WII, 2WIN, 2WY7, 2WY8, 2XQW, 2XWB, 2XWJ, 3D5R, 3D5S, 3G6J, 3L3O, 3L5N, 3NMS, 3OED, 3OHX, 3OXU, 3RJ3, 3T4A, 4HW5, 4HWJ, 4I6O, 4M76, 4ZH1, 5FOB, 5FO9, 5FO7, 5FO8, 5FOA
Identifiers
Aliases	C3, AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1, HEL-S-62p, complement component 3
External IDs	OMIM: 120700 MGI: 88227 HomoloGene: 68031 GeneCards: C3
Genetically Related Diseases
age related macular degeneration[1]
Gene ontology Molecular function • C5L2 anaphylatoxin chemotactic receptor binding • protein binding • endopeptidase inhibitor activity • receptor binding • serine-type endopeptidase activity Cellular component • blood microparticle • plasma membrane • extracellular space • extracellular region • extracellular exosome Biological process • G-protein coupled receptor signaling pathway • positive regulation of phagocytosis • positive regulation of protein phosphorylation • complement activation, alternative pathway • lipid metabolic process • immune system process • complement activation • positive regulation of lipid storage • positive regulation of type IIa hypersensitivity • fatty acid metabolic process • positive regulation of angiogenesis • positive regulation of G-protein coupled receptor protein signaling pathway • positive regulation of apoptotic cell clearance • immune response • complement activation, classical pathway • regulation of immune response • positive regulation of activation of membrane attack complex • positive regulation of vascular endothelial growth factor production • inflammatory response • positive regulation of glucose transport • regulation of complement activation • signal transduction • negative regulation of endopeptidase activity • regulation of triglyceride biosynthetic process • proteolysis • innate immune response Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	718	12266
Ensembl	ENSG00000125730	ENSMUSG00000024164
UniProt	P01024	P01027
RefSeq (mRNA)	NM_000064	NM_009778
RefSeq (protein)	NP_000055.2	NP_033908.2
Location (UCSC)	Chr 19: 6.68 – 6.73 Mb	Chr 17: 57.2 – 57.23 Mb
PubMed search	[2]	[3]
Wikidata

Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.^[4][5]

Function

C3 plays a central role in the activation of complement system.^[6] Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.^[7][8]

One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the proteolytic cleavage of C3 into C3a and C3b, generated during activation through the classical pathway as well as the lectin pathway. C3a is an anaphylotoxin and the precursor of some cytokines such as ASP, and C3b serves as an opsonizing agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). Once C3 is activated to C3b, it exposes a reactive thioester that allows the peptide to covalently attach to any surface that can provide a nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase.

C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein (Factor H, CR1, MCP or C4BP) to supply cofactor activity.

Structure

Several crystallographic structures of C3 have been determined^[9] and reveal that this protein contains 13 domains.^{[10][11][12][13]}

Clinical use

Levels of C3 in the blood may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with Systemic Lupus Eritematosus ^[14] and some types of kidney disease such as post-infectious glomerulonephritis, membranoproliferative glomerulonephritis, and shunt nephritis.

.

Interactions

Complement component 3 has been shown to interact with Factor H.^[15][16]

Pathology

Deficiencies in C3 lead to generic infections, usually fatal to the newborn.^[17]

References

Further reading

External links

• GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome
• OMIM entries on Atypical Hemolytic-Uremic Syndrome
• GeneReviews/NCBI/NIH/UW entry on Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II
• Complement C3 at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.