Complement C3 (C3)
The protein contains 1663 amino acids for an estimated molecular weight of 187148 Da.
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.', 'Acts as a chemoattractant for neutrophils in chronic inflammation.', '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). (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Amyloid-beta clearance
Cell surface receptor signaling pathway involved in cell-cell signaling
Cellular protein metabolic process
Complement activation
Complement activation, alternative pathway
Complement activation, classical pathway
Complement-dependent cytotoxicity
Complement-mediated synapse pruning
Fatty acid metabolic process
G protein-coupled receptor signaling pathway
Immune response
Inflammatory response
Innate immune response
Neuron remodeling
Neutrophil degranulation
Oviduct epithelium development
Phagocytosis, engulfment
Positive regulation of activation of membrane attack complex
Positive regulation of angiogenesis
Positive regulation of apoptotic cell clearance
Positive regulation of G protein-coupled receptor signaling pathway
Positive regulation of glucose transmembrane transport
Positive regulation of lipid storage
Positive regulation of phagocytosis, engulfment
Positive regulation of protein phosphorylation
Positive regulation of receptor-mediated endocytosis
Positive regulation of type IIa hypersensitivity
Positive regulation of vascular endothelial growth factor production
Post-translational protein modification
Purinergic nucleotide receptor signaling pathway
Regulation of complement activation
Regulation of immune response
Regulation of triglyceride biosynthetic process
Response to bacterium
Signal transduction
Vertebrate eye-specific patterning
The reference OMIM entry for this protein is 120700
Complement component 3; c3 c3a, included
C3b, included
C3c, included
C3d, included
Acylation-stimulating protein, included; asp, included
DESCRIPTION
The complement system is an important mediator of natural and acquired immunity. It consists of approximately 30 proteins that can exhibit catalytic activity, function as regulators, or act as cellular surface receptors. These components normally circulate in inactive forms and are activated by the classical, alternative, or lectin pathways. Complement component 3 plays a central role in all 3 activation pathways (summary by Reis et al., 2006). For a review of the complement system and its components, see Degn et al. (2011).CLONING
De Bruijn and Fey (1985) presented the complete coding sequence of the C3 gene and the derived amino acid sequence. C3 is an acute phase reactant; increased synthesis of C3 is induced during acute inflammation. The liver is the main site of synthesis, although small amounts are also produced by activated monocytes and macrophages. A single chain precursor (pro-C3) of approximately 200 kD is found intracellularly; the cDNA shows that it comprises 1,663 amino acids. This is processed by proteolytic cleavage into alpha (C3a) and beta (C3b) subunits which in the mature protein are linked by disulfide bonds. Pro-C3 contains a signal peptide of 22 amino acid residues, the beta chain (645 residues) and the alpha chain (992 residues). The 2 chains are joined by 4 arginine residues that are not present in the mature protein. Human C3 has 79% identity to mouse C3 at the nucleotide level and 77% at the amino acid level.BIOCHEMICAL FEATURES
- Crystal Structure Janssen et al. (2005) presented the crystal structures of native C3 and its final major proteolytic fragment C3c. The structures revealed 13 domains, 9 of which were unpredicted, and suggested that the proteins of the alpha-2-macroglobulin family evolved from a core of 8 homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha chain, including movement of a critical interaction site through a ring formed by the domains of the beta chain, indicated an unprecedented, conformation-dependent mechanism of activation, regulation, and biologic function of C3. Janssen et al. (2006) presented the crystal structure at 4-angstrom resolution of the activated complement protein C3b and described the conformation rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 angstroms away from the buried site in native C3. Marked domain rearrangements in the alpha chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B (CFB; 138470) and several complement regulators. The structural data indicated that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. Wiesmann et al. (2006) presented the crystal structure of C3b in complex with CRIG (300353) and, using CRIG mutants, provided evidence that CRIG acts as an inhibitor of the alternative pathway of complement. The structure shows that activation of C3 induces major structural rearrangements, including a dramatic movement (greater than 80 angstroms) of the thioester bond-containing domain through which C3b attaches to pathogen surfaces. Wies ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for C3
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 120700 was added.