Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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DAVID Functional Annotation Table
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SOS Ras/Rac guanine nucleotide exchange factor 1(SOS1) SOS Ras/Rac guanine nucleotide exchange factor 1(SOS1) Related Genes Homo sapiens
CHROMOSOME 2,
CYTOBAND 2p22-p21,
ENSEMBL_GENE_ID ENSG00000115904,
GENERIF_SUMMARY mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1, there is an HF (histone H2A) motif located upstream of the DH domain in the hSos1 protein, study of tandem histone folds in the structure of the N-terminal segment of the ras activator Son of Sevenless, p21Ras, hSOS1, and p120GAP are not involved in polycystic ovary disease, The full-length Grb2 proteins mediate negative regulation of the intrinsic Ras guanine-nucleotide exchange activity of hSos1., In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL., increased fibroblast numbers and collagen matrix changes are associated with mutation [in hereditary gingival fibromatosis], crystal structure of the Rem and Cdc25 domains of Sos1 determined at 2.0-A resolution in the absence of Ras, Missense mutations in SOS1 associated with Noonan syndrome., SOS1 mutants as a major cause of Noonan syndrome., The unusual RasGRP-SOS interplay results in sensitive and robust Ras activation that cannot be achieved with either activator alone., it was concluded that SOS1 does not act as a proto-oncogene in juvenile myelomonocytic leukemia, The pleckstrin homology domain of human SOS1 seems to function as a sensor domain in detecting the prenylation status of Ras bound to the distal site of SOS1., Our findings establish a crucial role for PLD2 in the coupling of extracellular signals to Sos-mediated Ras activation, and provide new insights into the spatial coordination of this activation event., study reports that mutant SOS1 contributes an increased and sustained activation of ERK signaling in Hereditary gingival fibromatosis 1 fibroblasts under serum-starved conditions, SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome, findings suggest that SOS1 is not a significant human oncogene in most cancers. Furthermore, NS patients with SOS1 mutations may not be at increased risk of developing cancer, Study shows that SOS responds to the membrane density of Ras molecules, to their GTP loading and to the concentration of phosphatidylinositol-4,5-bisphosphate, and that the integration of these signals potentiates the release of autoinhibition., Patients with SOS1 mutations range from Noonan syndrome to cardio-facio-cutaneous syndrome., Structural basis of the differential binding of the SH3 domains of GRB2 and SOS1 are reported., Mutational analysis of SOS1 gene in acute myeloid leukemia., Mutations in the SOS1 are associated with Noonan syndrome., Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation, analysis of SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions, the involvement of SOS1 gene in a family with the Noonan-like/multiple giant cell lesion phenotype, The tandem SH3A and SH3B domains of Tks5 constitute a versatile module for the implementation of isoform-specific protein-protein interactions., Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men., First report describing different tumor types in Noonan syndrome with germline SOS1 mutations., The binding of Grb2 adaptor to its downstream partners Sos1 and Gab1 docker is under tight allosteric regulation., A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway., a new crystal structure of SOS at 3.2 A resolution was presented that contains the histone domain and the DH-PH unit in addition to the catalytic segment (SOSHDPC, residues 1-1049)., Sos-histone domain plays a critical role in governing the catalytic output of Sos through the coupling of membrane recruitment to the release of autoinhibition., Noonan-like/multiple giant cell lesion syndrome with mutations in the SOS1 gene, Based on our results, it is possible that a subtle dysfunction (expression) of the SOS1 gene is involved in the development of the most common male reproductive tract disorder - unilateral or bilateral cryptorchidism, Noonan syndrome is due to a SOS1 missense mutation and rhabdomyosarcoma., two unrelated patients with Noonan syndrome carrying the same heterozygous SOS1 missense mutation (c.1867T > A/p.F623I), mutation analysis performed on RAF1, SOS1, and GRB2, in 24 Noonan syndrome patients previously found to be negative for PTPN11 and KRAS mutations; SOS1 may have a role of modifier gene that might contribute the variable expressivity of the disease, Multiple decisive phosphorylation sites for the negative feedback regulation of SOS1 via ERK., This study investigated the regulation of the previously uncharacterized SOS1 gene promoter by the aryl hydrocarbon receptor and its ligands in HepG2 cells., this report expanded the available information about the molecular diversity of SOS1 mutations underlying Noonan syndrome, and have provided a more comprehensive assessment of the clinical features associated with those molecular lesions., The researchers found evidence that there were significant differences between the D2S441 locus in the Maghreb population and other populations., Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes., We present a stochastic mathematical model describing intra-molecular regulation of hSos1 activity., CIIA functions as a molecular switch for the GEF activity of SOS1, directing this activity toward Rac1., SOS1 over-expression may play a role in the regulation of the RAS/mitogen-activated protein kinase pathway in the skin, in the hair follicle proliferation and cell cycle, suggesting new perspectives in understanding the pathogenesis of hirsutism., T-cell antigen receptor (TCR)-mediated Erk activation requires RasGRP1, but not Grb2/Sos., multiple binding sites within Sos1 provide a physical route for Grb2 to hop in a flip-flop manner from one site to the next through facilitated diffusion, and such rapid exchange forms the basis of cooperativity driving bivalent binding of Grb2 to Sos1, Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2, Oncogenic K-Ras promotes the activation of wild-type H- and N-Ras and this activation is mediated by oncogenic K-Ras-dependent allosteric stimulation of Sos., Although Sos1 and Gab1 recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in lieu of a composite Sos1-Grb2-Gab1 ternary complex., The SOS1 T158A mutation altered the phosphorylation of gene products involved in both RAS/MAPK and PI3K/AKT pathways., The PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations., study established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation, MiR-124 inhibits the growth of glioblastoma through the downregulation of SOS1., sustained Erk signaling and T-cell activation depend on both Sos1 and RasGRP1., CIIA functions as a negative modulator of the SOS1-Ras signaling events initiated by peptide growth factors including EGF., HGF-related mutation g.126,142-126,143insC in exon 21 was not found in any of the 6 affected individuals from three families., Increased expression of SOS1 increases NFkappaB activation in several types of cancer cells, and ablation of SOS1 inhibits EGF-induced NFkappaB activation in these cells, indicating that SOS1 is a component of the pathway connecting EGFR to NFkappaB activation., SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1., These data demonstrated the negative regulation between miR-146a and SOS1 and between miR-370 and GADD45beta and that these regulations are influenced by enterovirus 71 to induce apoptosis., Stabilized alpha helices of son of sevenless 1 directly inhibit wild-type and mutant forms of KRAS., The present study provides a first evidence of allelic imbalance of SOS1 and pinpoints this condition as a possible mechanism underlying a different penetrance of some SOS1-mutated alleles in unrelated carriers, Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme., In non-apoptotic cells, nuclear EGFR induced SOS1 expression by directly binding to the SOS1 promoter., rs963731 is associated with corticobasal degeneration., findings suggest that targeting the Src/Abl/Sos1/Rac pathway may represent a double-edged sword to control both cancer-invasive capacities and cancer-related inflammation., Ras.GDP weakly binds to the catalytic but not to the allosteric site of Sos.,
OMIM_DISEASE Fibromatosis, gingival, 1, Noonan syndrome 4,
SP_COMMENT disease:Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:135300]; also designated GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common., disease:Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common., function:Promotes the exchange of Ras-bound GDP by GTP., online information:Son of sevenless entry, similarity:Contains 1 DH (DBL-homology) domain., similarity:Contains 1 N-terminal Ras-GEF domain., similarity:Contains 1 PH domain., similarity:Contains 1 Ras-GEF domain., subunit:Interacts with GRB2. Forms a complex with phosphorylated MUC1 and GRB2 (via its SH3 domains). Interacts with phosphorylated LAT2., tissue specificity:Expressed in gingival tissues.,
SOS Ras/Rho guanine nucleotide exchange factor 2(SOS2) SOS Ras/Rho guanine nucleotide exchange factor 2(SOS2) Related Genes Homo sapiens
CHROMOSOME 14,
CYTOBAND 14q21,
ENSEMBL_GENE_ID ENSG00000100485,
GENERIF_SUMMARY Significant association of single nucleotide polymorphism within three genes--PPARgamma, SOS2, and PCK1--with Alzheimer's disease, was confirmed., Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation, intracellular Francisella tularensis novicida triggers temporal and early activation of Ras through the SOS2/GrB2/PKCalpha/PKCbetaI quaternary complex; Ras signalling by intracellular F. tularensis is essential for intracellular proliferation in the cytosol, multicenter pharmacogenetic study in children (ages 6-11), We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies., Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome,
OMIM_DISEASE Noonan syndrome 9,
SP_COMMENT function:Promotes the exchange of Ras-bound GDP by GTP., online information:Son of sevenless entry, similarity:Contains 1 DH (DBL-homology) domain., similarity:Contains 1 N-terminal Ras-GEF domain., similarity:Contains 1 PH domain., similarity:Contains 1 Ras-GEF domain.,