SOS1

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Protein-coding gene in the species Homo sapiens

title: "SOS1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["gtp-binding-protein-regulators"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/gtp-binding-protein-regulators" source: "https://en.wikipedia.org/wiki/SOS1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene.

Function

SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with Ras proteins to phosphorylate GDP into GTP, or from an inactive state to an active state to signal cell proliferation. RAS genes (e.g., MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae Cdc25 gene product (not to be confused with the S. pombe Cdc25). Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with the catalytic domain of Cdc25. Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange.

Clinical significance

Recent studies also show that mutations in Sos1 can cause Noonan syndrome and hereditary gingival fibromatosis type 1. Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes. activators of the MAP kinase pathway.

Inhibitors and activators

;Inhibitors

;Activators

  • VUBI1, was reported by Fesik et al. in 2018 along with other benzimidazole-derived SOS1 activators.

;PROTACs

Interactions

SOS1 has been shown to interact with:

References

References

  1. (October 1993). "Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively". Genomics.
  2. (September 2000). "Refinement of the locus for autosomal dominant hereditary gingival fibromatosis (GINGF) to a 3.8-cM region on 2p21". Genomics.
  3. "Entrez Gene: SOS1 son of sevenless homolog 1 (Drosophila)".
  4. (January 2007). "Germline gain-of-function mutations in SOS1 cause Noonan syndrome". Nature Genetics.
  5. (April 2002). "A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1". American Journal of Human Genetics.
  6. (December 2001). "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome". Nature Genetics.
  7. (February 2019). "Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction". Proceedings of the National Academy of Sciences of the United States of America.
  8. (12 June 2018). "Donated Chemical Probes".
  9. (January 2021). "BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition". Cancer Discovery.
  10. (June 2021). "Targeting Son of Sevenless 1: The pacemaker of KRAS". Current Opinion in Chemical Biology.
  11. (October 2018). "Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS". Journal of Medicinal Chemistry.
  12. (February 1995). "Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS". Molecular and Cellular Biology.
  13. (September 1999). "EPS8 and E3B1 transduce signals from Ras to Rac". Nature.
  14. (January 2004). "The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway". Molecular Biology of the Cell.
  15. (February 2000). "The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties". The EMBO Journal.
  16. (February 1998). "N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains". Molecular and Cellular Biology.
  17. (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB Journal.
  18. (May 1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell.
  19. (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". The EMBO Journal.
  20. (March 1994). "A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". The Journal of Biological Chemistry.
  21. (May 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proceedings of the National Academy of Sciences of the United States of America.
  22. (March 2003). "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nature Biotechnology.
  23. (December 1998). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc". Oncogene.
  24. (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene.
  25. (July 1996). "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking". Blood.
  26. (May 1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature.
  27. (May 1994). "SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases". The Journal of Biological Chemistry.
  28. (May 1999). "16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells". Molecular Endocrinology.
  29. (August 1995). "Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR". The Journal of Biological Chemistry.
  30. (March 2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". The EMBO Journal.
  31. (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood.
  32. (May 1999). "hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways". Molecular and Cellular Biology.
  33. (December 1999). "High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc-Grb2-Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase". Journal of Immunology.
  34. (May 2002). "Differential effect of the inhibition of Grb2-SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement". The Biochemical Journal.
  35. (January 1997). "Multiple Grb2-protein complexes in human cancer cells". International Journal of Cancer.
  36. (May 1994). "Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells". The Journal of Biological Chemistry.
  37. (March 2003). "Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS". Cell.
  38. (July 1998). "The structural basis of the activation of Ras by Sos". Nature.
  39. (September 1995). "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein". Cancer Research.
  40. (April 2001). "Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland". The Journal of Biological Chemistry.
  41. (October 1996). "Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor". The Journal of Biological Chemistry.
  42. (January 1999). "Characterization of interactions of Nck with Sos and dynamin". Cellular Signalling.
  43. (March 1995). "Binding of NCK to SOS and activation of ras-dependent gene expression". Molecular and Cellular Biology.
  44. (February 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". The Journal of Biological Chemistry.
  45. (July 2000). "Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1". Biochemistry.
  46. (August 2000). "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1". European Journal of Immunology.
  47. (October 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochemical and Biophysical Research Communications.
  48. (July 1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Molecular and Cellular Biology.
  49. (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochemical and Biophysical Research Communications.

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gtp-binding-protein-regulators