SORBS1

CAP/Ponsin is_associated_with::protein, also known as Sorbin and SH3 domain-containing protein 1 is a is_associated_with::protein that in humans is encoded by the SORBS1 is_associated_with::gene. CAP/Ponsin is part of a small family of adaptor proteins that regulate is_associated_with::cell adhesion, is_associated_with::growth factor signaling and cytoskeletal formation. CAP/Ponsin is mainly expressed in heart, is_associated_with::skeletal muscle, is_associated_with::liver, is_associated_with::adipose tissue, and is_associated_with::macrophages; in striated muscle tissue, CAP/Ponsin is localized to is_associated_with::costamere structures.

Structure
CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa. CAP/Ponsin is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part. These proteins contain a conserved sorbin homology (SOHO) domain and three is_associated_with::SH3 domains, and CAP/Ponsin is expressed in heart, is_associated_with::skeletal muscle, is_associated_with::liver, is_associated_with::adipose tissue, and is_associated_with::macrophages.

Function
In muscle, CAP/Ponsin plays a role in the formation of mature is_associated_with::costameres from is_associated_with::focal adhesion-like contacts during assembly of the contractile apparatus, as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology. In a mouse model of viral is_associated_with::myocarditis due to is_associated_with::Coxsackievirus infection, CAP/Ponsin stabilized antiviral type I is_associated_with::interferon production and was protective against is_associated_with::apoptosis and cytotoxicity. CAP/Ponsin has also been shown to be a major regulator of is_associated_with::insulin-stimulated signaling and regulation of is_associated_with::glucose uptake, by potentiating is_associated_with::insulin-induced is_associated_with::phosphorylation and recruitment of CBL to a is_associated_with::lipid raft signaling complex involving flotillin. A role for CAP/Ponsin in is_associated_with::macrophage function was illuminated by the finding that mice harboring SORBS1-deficient macrophages in is_associated_with::bone marrow was protective against high-fat diet-induced is_associated_with::insulin resistance and showed reduced is_associated_with::inflammation. In non-muscle cells, CAP/Ponsin inhibits cell spreading and is_associated_with::focal adhesion turnover, as its is_associated_with::siRNA-mediated knockdown resulted in enhanced PAK/MEK/ERK activation and cell migration.

Clinical Significance
CAP/Ponsin was demonstrated to be down-regulated in end-stage is_associated_with::heart failure patients; an effect that was restored upon mechanical unloading. A is_associated_with::single nucleotide polymorphism in SORBS1 was found to be associated with is_associated_with::type 2 diabetes and is_associated_with::obesity.

Interactions
SORBS1 has been shown to interact with:


 * CBL,
 * is_associated_with::FLOT1,
 * is_associated_with::INPPL1,
 * is_associated_with::INSM1,
 * is_associated_with::MLLT4,
 * is_associated_with::PXN, and
 * is_associated_with::Vinculin.