SOS1, or Son of Sevenless homolog 1, is a critical guanine nucleotide exchange factor (GEF) within the SOS gene family that plays a pivotal role in regulating intracellular signaling by activating RAS, a small GTPase. As a multi-domain protein characterized by structural motifs such as Dbl homology (DH) and pleckstrin homology (PH) domains, SOS1 localizes to the plasma membrane where it is recruited by adaptor proteins like GRB2 following ligand-induced activation of receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR). Its primary molecular function is to catalyze the exchange of GDP for GTP on RAS, thereby switching RAS from an inactive to an active state and initiating downstream signaling cascades, most notably the MAPK/ERK pathway, which governs essential cellular processes including proliferation, differentiation, and survival. Dysregulation of SOS1 function, often resulting from gain-of-function missense mutations such as G434R, leads to constitutive activation of the RAS-MAPK axis, a hallmark of various developmental disorders like Noonan syndrome, which is clinically characterized by cardiac defects, distinctive facial features, and growth retardation. In the context of oncology, somatic or germline mutations in SOS1 that enhance its GEF activity or overexpression of the gene can drive excessive cell proliferation and contribute to the pathogenesis of multiple malignancies, including colorectal and lung cancers. Consequently, the SOS1-RAS interaction interface has emerged as a promising therapeutic target, with investigational agents such as BI-3406 designed to disrupt this interaction and thereby inhibit aberrant RAS-driven signaling in cancer cells.
Subcellular localization of SOS1 (and its protein):
Gene Ontology (GO) terms for SOS1:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 4014 Ras signaling pathway [PATH:hsa04014] |
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 4012 ErbB signaling pathway [PATH:hsa04012] |
| 4630 Jak-STAT signaling pathway [PATH:hsa04630] |
| 4068 FoxO signaling pathway [PATH:hsa04068] |
| 4151 PI3K-Akt signaling pathway [PATH:hsa04151] |
| 4810 Regulation of actin cytoskeleton [PATH:hsa04810] |
| 4510 Focal adhesion [PATH:hsa04510] |
| 4540 Gap junction [PATH:hsa04540] |
| 4650 Natural killer cell mediated cytotoxicity [PATH:hsa04650] |
| 4660 T cell receptor signaling pathway [PATH:hsa04660] |
| 4662 B cell receptor signaling pathway [PATH:hsa04662] |
| 4664 Fc epsilon RI signaling pathway [PATH:hsa04664] |
| 4062 Chemokine signaling pathway [PATH:hsa04062] |
| 4910 Insulin signaling pathway [PATH:hsa04910] |
| 4912 GnRH signaling pathway [PATH:hsa04912] |
| 4915 Estrogen signaling pathway [PATH:hsa04915] |
| 4917 Prolactin signaling pathway [PATH:hsa04917] |
| 4722 Neurotrophin signaling pathway [PATH:hsa04722] |
| 4320 Dorso-ventral axis formation [PATH:hsa04320] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5231 Choline metabolism in cancer [PATH:hsa05231] |
| 5206 MicroRNAs in cancer [PATH:hsa05206] |
| 5205 Proteoglycans in cancer [PATH:hsa05205] |
| 5214 Glioma [PATH:hsa05214] |
| 5221 Acute myeloid leukemia [PATH:hsa05221] |
| 5220 Chronic myeloid leukemia [PATH:hsa05220] |
| 5211 Renal cell carcinoma [PATH:hsa05211] |
| 5215 Prostate cancer [PATH:hsa05215] |
| 5213 Endometrial cancer [PATH:hsa05213] |
| 5223 Non-small cell lung cancer [PATH:hsa05223] |
| 5034 Alcoholism [PATH:hsa05034] |
| 5160 Hepatitis C [PATH:hsa05160] |
| Name |
|---|
| Activation of Rac |
| Adaptive Immune System |
| Antigen activates B Cell Receptor (BCR) leading to generation of second messengers |
| Axon guidance |
| Cell death signalling via NRAGE, NRIF and NADE |
| Cell surface interactions at the vascular wall |
| Constitutive Signaling by EGFRvIII |
| Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants |
| Cytokine Signaling in Immune system |
| DAP12 interactions |
| DAP12 signaling |
| Developmental Biology |
| Disease |
| Diseases of signal transduction |
| Downstream signal transduction |
| Downstream signaling of activated FGFR1 |
| Downstream signaling of activated FGFR2 |
| Downstream signaling of activated FGFR3 |
| Downstream signaling of activated FGFR4 |
| EGFR Transactivation by Gastrin |
| Fc epsilon receptor (FCERI) signaling |
| FCERI mediated Ca+2 mobilization |
| FCERI mediated MAPK activation |
| FRS-mediated FGFR1 signaling |
| FRS-mediated FGFR2 signaling |
| FRS-mediated FGFR3 signaling |
| FRS2-mediated FGFR4 signaling |
| G alpha (12/13) signalling events |
| Gastrin-CREB signalling pathway via PKC and MAPK |
| GPCR downstream signaling |
| GRB2 events in EGFR signaling |
| GRB2 events in ERBB2 signaling |
| GRB2:SOS provides linkage to MAPK signaling for Integrins |
| Hemostasis |
| IGF1R signaling cascade |
| Innate Immune System |
| Insulin receptor signalling cascade |
| Integrin alphaIIb beta3 signaling |
| Interleukin receptor SHC signaling |
| Interleukin-2 signaling |
| Interleukin-3, 5 and GM-CSF signaling |
| IRS-mediated signalling |
| IRS-related events |
| IRS-related events triggered by IGF1R |
| NCAM signaling for neurite out-growth |
| NGF signalling via TRKA from the plasma membrane |
| NRAGE signals death through JNK |
| p75 NTR receptor-mediated signalling |
| Platelet activation, signaling and aggregation |
| Platelet Aggregation (Plug Formation) |
| Regulation of KIT signaling |
| Rho GTPase cycle |
| Role of LAT2/NTAL/LAB on calcium mobilization |
| SHC-mediated cascade:FGFR1 |
| SHC-mediated cascade:FGFR2 |
| SHC-mediated cascade:FGFR3 |
| SHC-mediated cascade:FGFR4 |
| SHC-mediated signalling |
| SHC-related events |
| SHC-related events triggered by IGF1R |
| SHC1 events in EGFR signaling |
| SHC1 events in ERBB2 signaling |
| SHC1 events in ERBB4 signaling |
| Signal attenuation |
| Signaling by EGFR |
| Signaling by EGFR in Cancer |
| Signaling by EGFRvIII in Cancer |
| Signaling by ERBB2 |
| Signaling by ERBB4 |
| Signaling by FGFR |
| Signaling by FGFR in disease |
| Signaling by FGFR1 |
| Signaling by FGFR1 in disease |
| Signaling by FGFR1 mutants |
| Signaling by FGFR2 |
| Signaling by FGFR2 in disease |
| Signaling by FGFR2 mutants |
| Signaling by FGFR3 |
| Signaling by FGFR3 in disease |
| Signaling by FGFR3 mutants |
| Signaling by FGFR4 |
| Signaling by FGFR4 in disease |
| Signaling by FGFR4 mutants |
| Signaling by GPCR |
| Signaling by Insulin receptor |
| Signaling by Interleukins |
| Signaling by Ligand-Responsive EGFR Variants in Cancer |
| Signaling by PDGF |
| Signaling by Rho GTPases |
| Signaling by Robo receptor |
| Signaling by SCF-KIT |
| Signaling by the B Cell Receptor (BCR) |
| Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) |
| Signalling by NGF |
| Signalling to ERKs |
| Signalling to RAS |
| SOS-mediated signalling |
| Tie2 Signaling |
| Disease | Score | NofPmids | NofSnps | Source |
| Noonan Syndrome 4 | 0.44 | 6 | 23 | CLINVAR_CTD_human_MGD_UNIPROT |
| Noonan Syndrome | 0.392971407 | 35 | 9 | BeFree_CLINVAR_CTD_human_GAD_LHGDN_ORPHANET |
| Hereditary gingival fibromatosis | 0.242171535 | 8 | 0 | BeFree_CTD_human_ORPHANET |
| Fibromatosis, Gingival | 0.008715934 | 4 | 0 | BeFree_LHGDN |
| Neoplasm Metastasis | 0.008414698 | 31 | 1 | BeFree |
| Glioma | 0.006710102 | 17 | 0 | BeFree_GAD |
| Congenital Heart Defects | 0.004734064 | 2 | 0 | GAD |
| Malignant neoplasm of breast | 0.00434307 | 16 | 1 | BeFree |
| Liver carcinoma | 0.00434307 | 16 | 0 | BeFree |
| Breast Carcinoma | 0.004071628 | 15 | 1 | BeFree |
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