Domain

Anaphylatoxin/fibulin (IPR000020)

Short name: Anaphylatoxin/fibulin

Domain relationships

Description

This entry represents C3a, C4a and C5a anaphylatoxins, which are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to a three-fold repeat in fibulins.

Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [PMID: 1431125]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [PMID: 2777798]. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [PMID: 2777798, PMID: 3081348]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [PMID: 3081348]. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [PMID: 3081348]. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges [PMID: 3081348].

Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers [PMID: 2269669, PMID: 12778127]. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilised by three disulphide bridges in the pattern Cys1-4, Cys2-5 and Cys3-6 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats [PMID: 8245130].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0005576 extracellular region

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE profiles
SMART
Pfam