Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur (PubMed:19666512). Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently (PubMed:12460571, PubMed:19666512). G1 and G4 bind two Ca(2+) in a type I and in a type II manner (PubMed:12460571, PubMed:19666512). G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner (PubMed:12460571, PubMed:19666512). Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4 (PubMed:12460571, PubMed:19666512). Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface (PubMed:12460571, PubMed:19666512). Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin (PubMed:12460571, PubMed:19666512). Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin (Probable).
Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed (PubMed:19666512). Plays a role in ciliogenesis (PubMed:20393563).
Amyloidosis, hereditary systemic 4, Finnish type
AMYLD4
A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD4 is due to gelsolin amyloid deposition and is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure. AMYLD4 is usually inherited in an autosomal dominant pattern. However, homozygotes with a more severe phenotype have also been reported.
None
The disease is caused by variants affecting the gene represented in this entry.
Phosphorylation on Tyr-86, Tyr-409, Tyr-465, Tyr-603 and Tyr-651 in vitro is induced in presence of phospholipids.
Belongs to the villin/gelsolin family.
Phagocytic cells, platelets, fibroblasts, nonmuscle cells, smooth and skeletal muscle cells.
Gelsolin, AGEL, Actin-depolymerizing factor, Brevin, ADF, GSN
Proteins
Neuroscience
80641Da
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