Disease relevance of SORBS1

• Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes [1].
• In human hepatoma Hep3B cells, SORBS1 was partly dissociated from the insulin receptor complex and bound to c-Abl protein upon insulin stimulation [2].
• Frequency of the T228A polymorphism in the SORBS1 gene in children with premature pubarche and in adolescent girls with hyperandrogenism [3].

High impact information on SORBS1

• CAP/Ponsin belongs to the SoHo family of adaptor molecules that includes ArgBP2 and Vinexin [4].
• On phosphorylation of Cbl, the c-Cbl-associated protein (CAP)/Cbl complex dissociates from the insulin receptor and translocates to a lipid raft membrane fraction to form a ternary complex with flotillin [5].
• In conclusion, our results suggest that the A228 allele of the T228A polymorphism of the SORBS1 gene is a protective factor for both obesity and diabetes, and also imply that the SORBS1 gene plays an important role in the pathogenesis of human disorders with insulin resistance [1].
• The human homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might play a role in human disorders with insulin resistance [1].
• After scanning for a total of 13,136 bp in each of 40 chromosomes, we have identified 14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene [1].

Biological context of SORBS1

• Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B [2].
• No statistically significant relationships were found between the SORBS1 genotypes and body mass index or hormone status [3].
• R85 and CAP are generated by alternative splicing of the gene SH3P12 which we localized on chromosome 10q23-q24 [6].
• Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction [7].

Anatomical context of SORBS1

• In this report, we measured the SORBS1 mRNA levels in human adipose tissues [8].
• Ataxin-7 colocalizes with full-length R85 (R85FL) in co-transfected Cos-7 cells and with one of the SH3P12GPs in neuronal intranuclear inclusions in brain from a SCA7 patient [6].
• This interaction results on one hand in the recruitment of the soluble intracellular domain of teneurin-1 to the cell membrane enriched in CAP/ponsin [9].
• The intracellular domain of teneurin-1 interacts with MBD1 and CAP/ponsin resulting in subcellular codistribution and translocation to the nuclear matrix [9].
• SH3P12/CAP/ponsin, a gene product with a sorbin homology domain and three consecutive SH3 domains in the carboxy-terminus, has been isolated from murine adipocytes and identified as an important adaptor during insulin signaling [2].

Associations of SORBS1 with chemical compounds

• Moreover, the relative SORBS1 mRNA levels in the omental depots were significantly related to BMI using either correlation analysis (gamma = -0.41, p = 0.0008) or multivariate linear regression analysis (beta = -0.20 +/- 0.09, p = 0.031) with adjustment for age, plasma glucose, serum insulin, triglyceride, and total cholesterol levels [8].
• The sorbin and SH3-domain-containing-1 (SORBS1) gene codes for c-Cbl-associated protein (CAP) involved in insulin-mediated glucose uptake [3].
• The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2 [10].

Other interactions of SORBS1

• The relative SORBS1 mRNA levels were quantified using real-time polymerase chain reaction [8].
• CONCLUSION(S): This SORBS1 polymorphism does not play a major role in premature pubarche, hyperandrogenism, and/or polycystic ovary syndrome in our patient population [3].
• The interaction between ataxin-7 and the SH3P12 gene products (SH3P12GPs) was confirmed by pull-down and co-immunoprecipitation [6].

Analytical, diagnostic and therapeutic context of SORBS1

• To search for possible novel regulators of c-Cbl, we purified a number of c-Cbl-associated proteins by affinity chromatography and identified them by mass spectrometry [11].
• We describe two techniques for radioimmunoassay of apolipoprotein A-I (apoA-I) in human plasma, each involving use of a non-ionic detergent, Tween-20, to expose antigenic sites, and one involving "IgG SORB" (a suspension of killed staphylococci) as a solid-phase separator [12].

References