SORBS1

CAP/Ponsin protein, also known as Sorbin and SH3 domain-containing protein 1 is a protein that in humans is encoded by the SORBS1 gene.^[5][6][7] It is part of a small family of adaptor proteins that regulate cell adhesion, growth factor signaling and cytoskeletal formation. It is mainly expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages; in striated muscle tissue, it is localized to costamere structures.

SORBS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DL3, 2ECZ, 2LJ0, 2MOX, 2O2W, 2O31, 2O9S, 2O9V, 4LN2, 4LNP
Identifiers
Aliases	SORBS1, CAP, FLAF2, R85FL, SH3D5, SH3P12, SORB1, sorbin and SH3 domain containing 1
External IDs	OMIM: 605264; MGI: 700014; HomoloGene: 83252; GeneCards: SORBS1; OMA:SORBS1 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q24.1 Start 95,311,771 bp[1] End 95,561,414 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19 C3|19 34.25 cM Start 40,294,753 bp[2] End 40,513,779 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in saphenous vein myocardium of left ventricle tail of epididymis cardiac muscle tissue of right atrium Descending thoracic aorta gastric mucosa popliteal artery tibial arteries right coronary artery right ventricle Top expressed in Rostral migratory stream tunica adventitia of aorta subcutaneous adipose tissue white adipose tissue intercostal muscle brown adipose tissue myocardium of ventricle paraventricular nucleus of hypothalamus globus pallidus tunica media of zone of aorta More reference expression data BioGPS More reference expression data
Gene ontology Molecular function insulin receptor binding cytoskeletal protein binding protein binding actin binding Cellular component cytosol centrosome membrane focal adhesion nuclear matrix adherens junction plasma membrane stress fiber cell junction zonula adherens membrane raft cytoskeleton nucleus insulin receptor complex cytoplasm Biological process positive regulation of glucose import positive regulation of glycogen biosynthetic process muscle contraction positive regulation of lipid biosynthetic process actin filament organization stress fiber assembly focal adhesion assembly cellular response to insulin stimulus cell-matrix adhesion positive regulation of signal transduction positive regulation of protein localization to plasma membrane insulin receptor signaling pathway positive regulation of insulin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10580 20411 Ensembl ENSG00000095637 ENSMUSG00000025006 UniProt Q9BX66 Q62417 RefSeq (mRNA) NM_001034954 NM_001034955 NM_001034956 NM_001034957 NM_001290294 NM_001290295 NM_001290296 NM_001290297 NM_001290298 NM_006434 NM_015385 NM_024991 NM_001377197 NM_001377198 NM_001377199 NM_001377200 NM_001377201 NM_001377202 NM_001377203 NM_001377204 NM_001377205 NM_001377206 NM_001377207 NM_001377208 NM_001377209 NM_001384447 NM_001384448 NM_001384449 NM_001384450 NM_001384451 NM_001384452 NM_001384453 NM_001384454 NM_001384455 NM_001384456 NM_001384457 NM_001384458 NM_001384459 NM_001384460 NM_001384461 NM_001384462 NM_001384463 NM_001384464 NM_001384465 NM_001034962 NM_001034963 NM_001034964 NM_009166 NM_178362 RefSeq (protein) NP_001030126 NP_001030127 NP_001030128 NP_001030129 NP_001277223 NP_001277224 NP_001277225 NP_001277226 NP_001277227 NP_006425 NP_056200 NP_079267 NP_001364126 NP_001364127 NP_001364128 NP_001364129 NP_001364130 NP_001364131 NP_001364132 NP_001364133 NP_001364134 NP_001364135 NP_001364136 NP_001364137 NP_001364138 NP_001030134 NP_001030135 NP_001030136 NP_033192 NP_848139 NP_001389984 NP_001389985 Location (UCSC) Chr 10: 95.31 – 95.56 Mb Chr 19: 40.29 – 40.51 Mb PubMed search [3] [4]
Wikidata
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Structure

CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa.^[8] It is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part.^[9] These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains, and CAP/Ponsin is expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages.^[8][10][11]

Function

In muscle, CAP/Ponsin plays a role in the formation of mature costameres from focal adhesion-like contacts during assembly of the contractile apparatus, as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology.^[12] In a mouse model of viral myocarditis due to Coxsackievirus infection, CAP/Ponsin stabilized antiviral type I interferon production and was protective against apoptosis and cytotoxicity.^[13] It has also been shown to be a major regulator of insulin-stimulated signaling and regulation of glucose uptake, by potentiating insulin-induced phosphorylation and recruitment of CBL to a lipid raft signaling complex involving flotillin.^[14] A role for it in macrophage function was illuminated by the finding that, in mice harboring SORBS1-deficient macrophages in bone marrow, it was protective against high-fat diet-induced insulin resistance and showed reduced inflammation.^[11] In non-muscle cells, it inhibits cell spreading and focal adhesion turnover, as its siRNA-mediated knockdown resulted in enhanced PAK/MEK/ERK activation and cell migration.^[15]

Clinical Significance

CAP/Ponsin was demonstrated to be down-regulated in end-stage heart failure patients; an effect that was restored upon mechanical unloading.^[12] A single nucleotide polymorphism in SORBS1 was found to be associated with type 2 diabetes and obesity.^[16]

Interactions

SORBS1 has been shown to interact with:

• CBL,^[17][18]
• FLOT1,^[6][17][19]
• INPPL1,^[18]
• INSM1,^[20]
• MLLT4,^[5]
• PXN,^[12] and
• Vinculin.^[5]