SORBS2

SORBS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4IGZ
Identifiers
Aliases	SORBS2, ARGBP2, PRO0618, sorbin and SH3 domain containing 2
External IDs	OMIM: 616349; MGI: 1924574; HomoloGene: 83295; GeneCards: SORBS2; OMA:SORBS2 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q35.1 Start 185,585,444 bp[1] End 185,956,652 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B1.1 Start 45,960,825 bp[2] End 46,280,943 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle popliteal artery tibial arteries myocardium of left ventricle right coronary artery cardiac muscle tissue of right atrium retinal pigment epithelium right adrenal cortex left adrenal cortex apex of heart Top expressed in otolith organ utricle gastrula myocardium of ventricle atrioventricular valve decidua atrium parotid gland piriform cortex left ventricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function structural constituent of cytoskeleton protein binding cytoskeletal anchor activity structural constituent of muscle RNA binding nucleic acid binding Cellular component cytoplasm cell projection membrane focal adhesion plasma membrane cell junction Z disc apical plasma membrane actin cytoskeleton perinuclear region of cytoplasm nucleus lamellipodium nucleoplasm Biological process cell growth involved in cardiac muscle cell development actin filament organization Notch signaling pathway biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8470 234214 Ensembl ENSG00000154556 ENSMUSG00000031626 UniProt O94875 Q3UTJ2 RefSeq (mRNA) NM_001145670 NM_001145671 NM_001145672 NM_001145673 NM_001145674 NM_001145675 NM_001270771 NM_003603 NM_021069 NM_001205219 NM_172752 NM_001310707 NM_001310708 RefSeq (protein) NP_001139142 NP_001139143 NP_001139144 NP_001139145 NP_001139146 NP_001139147 NP_001257700 NP_003594 NP_066547 NP_001192148 NP_001297636 NP_001297637 NP_766340 NP_001389592 NP_001389593 NP_001389594 NP_001389595 NP_001389596 NP_001389597 NP_001389598 NP_001389599 NP_001389600 NP_001389601 NP_001389602 NP_001389603 NP_001389604 Location (UCSC) Chr 4: 185.59 – 185.96 Mb Chr 8: 45.96 – 46.28 Mb PubMed search [3] [4]
Wikidata
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ArgBP2 protein, also referred to as Sorbin and SH3 domain-containing protein 2 is a protein that in humans is encoded by the SORBS2 gene.^[5][6] ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains. ArgBP2 is highly abundant in cardiac muscle cells at sarcomeric Z-disc structures, and is expressed in other cells at actin 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).^[6] ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains and three SH3 domains, which regulate cell adhesion, cytoskeletal organization and growth factor signaling; other members include CAP/ponsin and vinexin.^[7] The three SH3 domains are C-terminal, a serine-threonine rich domain^[8] resides in the middle, and the sorbin homology (SoHo) domain is N-terminal. The SH3 domains interact with Arg/Abl, vinculin.^[7] The SOHO domain interacts with flotillin found in lipid rafts.^[9]

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;^[8] 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;^[10] and also Pyk2 which promotes cytoskeletal remodeling.^[11] ArgBP2 binding with flotillin at lipid rafts may indicate a role for ArgBP2 in vesicle trafficking and signal transduction. flotillin in skeletal muscle cells exhibits a striated pattern^[12] suggesting localization to T-tubules or sarcoplasmic reticular cisternae, though no precise role has been determined in cardiac cells. In cardiac muscle cells, pull-down experiments discovered ArgBP2 in complex with alpha actinin-2, vinculin, spectrin, paxillin, Pyk2 and flotillin, suggesting that ArgBP2 may be involved in myofibril assembly and Z-band signaling in cardiomyocytes,^[13] though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hypertrophic signaling, as a potent paracrine-acting RNA molecule shown to induce cardiac hypertrophy in mice, miR-21, acts on both ArgBP2 and PDLIM5 to trigger the hypertrophic response.^[14]

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-myocardial infarction who died within 7 hours of the insult.^[15] Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect SORBS2.^[16]

Interactions

ArgBP2 has been shown to interact with:

References

Further reading