SORBS2

ArgBP2 is_associated_with::protein, also referred to as Sorbin and SH3 domain-containing protein 2 is a is_associated_with::protein that in humans is encoded by the SORBS2 is_associated_with::gene. ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains. ArgBP2 is highly abundant in is_associated_with::cardiac muscle cells at sarcomeric Z-disc structures, and is expressed in other cells at is_associated_with::actin is_associated_with::stress fibers and the nucleus.

Structure
ArgBP2 may exist in as many as 9 unique isoforms ranging from 52 kDa to 117 kDa (492 to 1100 amino acids). ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains and three is_associated_with::SH3 domains, which regulate cell adhesion, cytoskeletal organization and growth factor signaling; other members include CAP/ponsin and vinexin. The three is_associated_with::SH3 domains are C-terminal, a serine-threonine rich domain resides in the middle, and the sorbin homology (SoHo) domain is N-terminal. The SH3 domains interact with Arg/Abl, vinculin. The SOHO domain interacts with flotillin found in lipid rafts.

Function
The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that ArgBP2 functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. ArgBP2 contains several potential Abl phosphorylation sites; Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. In non-muscle cells, ArgBP2 bids Cbl which enhances the degradation of c-Abl; and also is_associated_with::Pyk2 which promotes cytoskeletal remodeling. ArgBP2 binding with flotillin at lipid rafts may indicate a role for ArgBP2 in vesicle trafficking and signal transduction. Interestingly, flotillin in is_associated_with::skeletal muscle cells exhibits a striated pattern suggesting localization to is_associated_with::T-tubules or sarcoplasmic reticular cisternae, though no precise role has been determined in is_associated_with::cardiac cells. In cardiac muscle cells, pull-down experiments discovered ArgBP2 in complex with alpha actinin-2, is_associated_with::vinculin, spectrin, is_associated_with::paxillin, is_associated_with::Pyk2 and flotillin, suggesting that ArgBP2 may be involved in is_associated_with::myofibril assembly and Z-band signaling in cardiomyocytes, though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hyertrophic signaling, as a potent paracrine-acting RNA molecule shown to induce is_associated_with::cardiac hypertrophy in mice, miR-21, acts on both ArgBP2 and is_associated_with::PDLIM5 to trigger the hypertrophic response.

Clinical Significance
Elevated levels of serum ArgBP2 and coordinate decreases in ArgBP2 in myocardial tissue were detected in the very early phase from patients post-is_associated_with::myocardial infarction who died within 7 hours of the insult. Chromosome 4 pericentric inversion has been observed in 10 patients, with associated is_associated_with::cardiac defects linked to terminal 4q35.1 deletions, which may affect SORBS2.

Interactions
ArgBP2 has been shown to interact with:


 * ABL,
 * is_associated_with::ABL2,
 * is_associated_with::ACTC1,
 * CBL,
 * is_associated_with::FLOT1,
 * is_associated_with::PTK2B,
 * is_associated_with::PLDN, and
 * VCL.