InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: C3

Summary

InnateDB Protein

IDBP-21800.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Protein Name

complement component 3

Synonyms

AHUS5; ARMD9; ASP; C3a; C3b; CPAMD1; HEL-S-62p;

Species

Homo sapiens

Ensembl Protein

ENSP00000245907

InnateDB Gene

IDBG-21798 (C3)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000250}.C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation. {ECO:0000250}.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). {ECO:0000269PubMed:10432298, ECO:0000269PubMed:15833747, ECO:0000269PubMed:16333141, ECO:0000269PubMed:19615750, ECO:0000269PubMed:2909530, ECO:0000269PubMed:8376604, ECO:0000269PubMed:9059512}.

Subcellular Localization

Secreted.

Disease Associations

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. {ECO:0000269PubMed:7961791, ECO:0000269Ref.49}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:17634448, ECO:0000269PubMed:24036952}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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. {ECO:0000269PubMed:18796626, ECO:0000269PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.Note=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.

Tissue Specificity

Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods. {ECO:0000269PubMed:15833747, ECO:0000269PubMed:9555951}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 37 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	37 [view]
Protein-Protein	36 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004866	endopeptidase inhibitor activity
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0031715	C5L2 anaphylatoxin chemotactic receptor binding

Biological Process

GO:0001798	positive regulation of type IIa hypersensitivity
GO:0001934	positive regulation of protein phosphorylation
GO:0001970	positive regulation of activation of membrane attack complex
GO:0006631	fatty acid metabolic process
GO:0006954	inflammatory response
GO:0006955	immune response
GO:0006956	complement activation
GO:0006957	complement activation, alternative pathway
GO:0006958	complement activation, classical pathway
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0010575	positive regulation vascular endothelial growth factor production
GO:0010828	positive regulation of glucose transport
GO:0010866	regulation of triglyceride biosynthetic process
GO:0010884	positive regulation of lipid storage
GO:0010951	negative regulation of endopeptidase activity
GO:0030449	regulation of complement activation
GO:0045087	innate immune response (InnateDB)
GO:0045745	positive regulation of G-protein coupled receptor protein signaling pathway
GO:0045766	positive regulation of angiogenesis
GO:0050766	positive regulation of phagocytosis
GO:0050776	regulation of immune response
GO:2000427	positive regulation of apoptotic cell clearance

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005886	plasma membrane
GO:0070062	extracellular vesicular exosome
GO:0072562	blood microparticle

Protein Structure and Domains

PDB ID

InterPro

IPR000020 Anaphylatoxin/fibulin
IPR001134 Netrin domain
IPR001599 Alpha-2-macroglobulin
IPR001840 Anaphylatoxin, complement system domain
IPR002890 Alpha-2-macroglobulin, N-terminal
IPR008930 Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid
IPR008993 Tissue inhibitor of metalloproteinases-like, OB-fold
IPR009048 Alpha-macroglobulin, receptor-binding
IPR011625 Alpha-2-macroglobulin, N-terminal 2
IPR011626 Alpha-macroglobulin complement component
IPR018081 Anaphylatoxin, complement system
IPR018933 Netrin module, non-TIMP type
IPR019565 Alpha-2-macroglobulin, thiol-ester bond-forming

PFAM