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SOS Ras/Rac guanine nucleotide exchange factor 1

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Target not currently curated in GtoImmuPdb

Target id: 3096

Nomenclature: SOS Ras/Rac guanine nucleotide exchange factor 1

Family: Rho GEFs

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1333 2p22.1 SOS1 SOS Ras/Rac guanine nucleotide exchange factor 1
Mouse - 1319 17 50.67 cM Sos1 SOS Ras/Rac guanine nucleotide exchange factor 1
Rat - 1319 6q11 Sos1 SOS Ras/Rac guanine nucleotide exchange factor 1
Previous and Unofficial Names Click here for help
GF1 | gingival fibromatosis, hereditary, 1 (GINGF) | HGF | son of sevenless homolog 1 (Drosophila) | SOS-1
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Ras guanine nucleotide exchange factor SOS1 (Rem-cdc25) in complex with small molecule inhibitor BAY-293 (compound 23)
PDB Id:  5OVI
Ligand:  BAY-293
Resolution:  2.2Å
Species:  Human
References:  2
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BAY-293 Small molecule or natural product Ligand has a PDB structure Hs Binding 7.7 pIC50 2
pIC50 7.7 (IC50 2.1x10-8 M) [2]
Description: Binding to SOS1 in vitro.
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0002260 lymphocyte homeostasis IGI
GO:0038095 Fc-epsilon receptor signaling pathway TAS
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GO:0001782 B cell homeostasis IEA
GO:0033081 regulation of T cell differentiation in thymus IEA
GO:0042129 regulation of T cell proliferation IEA
GO:2000973 regulation of pro-B cell differentiation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0038095 Fc-epsilon receptor signaling pathway TAS
click arrow to show/hide IEA associations
GO:0033081 regulation of T cell differentiation in thymus IEA
GO:0042129 regulation of T cell proliferation IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Immuno Process:  Immune system development
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033081 regulation of T cell differentiation in thymus IEA
GO:2000973 regulation of pro-B cell differentiation IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033081 regulation of T cell differentiation in thymus IEA
GO:0042129 regulation of T cell proliferation IEA
General Comments
SOS1 is a guanine nucleotide exchange factor that regulates the activation state of RAS GTPases. When the RAS/SOS1 complex forms RAS can reload with GTP and is activated. Inhibition of RAS/SOS1 formation prevents reloading with GTP and blocks RAS pathway activation.

Blocking the RAS/SOS1 interaction using small-molecules is being explored as a novel antiproliferative mechanism [1,3-4]. Of particular interest in cancer would be the ability to inhibit SOS1 interaction with the KRASG12C oncogenic mutant which drives proliferation in many human cancers [2].

References

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1. Burns MC, Howes JE, Sun Q, Little AJ, Camper DV, Abbott JR, Phan J, Lee T, Waterson AG, Rossanese OW et al.. (2018) High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling. Anal. Biochem., 548: 44-52. [PMID:29444450]

2. Hillig RC, Sautier B, Schroeder J, Moosmayer D, Hilpmann A, Stegmann CM, Werbeck ND, Briem H, Boemer U, Weiske J et al.. (2019) Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction. Proc. Natl. Acad. Sci. U.S.A., 116 (7): 2551-2560. [PMID:30683722]

3. Lu S, Jang H, Zhang J, Nussinov R. (2016) Inhibitors of Ras-SOS Interactions. ChemMedChem, 11 (8): 814-21. [PMID:26630662]

4. Winter JJ, Anderson M, Blades K, Brassington C, Breeze AL, Chresta C, Embrey K, Fairley G, Faulder P, Finlay MR et al.. (2015) Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation. J. Med. Chem., 58 (5): 2265-74. [PMID:25695162]

How to cite this page

Rho GEFs: SOS Ras/Rac guanine nucleotide exchange factor 1. Last modified on 09/09/2019. Accessed on 01/03/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3096.