Son of sevenless homolog 1 (SOS1) is a large cytosolic guanine nucleotide exchange factor that activates RAS (HRAS, KRAS, NRAS) downstream of receptor tyrosine kinases and immunoreceptors. It comprises an N-terminal tandem histone-fold region, a Dbl-homology (DH) and pleckstrin-homology (PH) unit, a catalytic module of Ras exchanger motif (REM) and CDC25-homology domains, and a C-terminal proline-rich tail. In resting cells SOS1 is autoinhibited: the histone and DH-PH domains occlude a distal allosteric Ras-binding site. On receptor activation the SH3 domains of the adaptor GRB2 bind PXXP motifs in the proline-rich tail and recruit SOS1 to phosphotyrosine sites at the plasma membrane, where PIP2 and Ras-GTP binding at the allosteric site relieve autoinhibition; the CDC25 domain then inserts a helical hairpin into Ras, displaces switch I and releases GDP so that GTP can load. Allosteric Ras-GTP binding makes SOS1 activation self-reinforcing, while ERK/RSK phosphorylation of the tail provides negative feedback. Through its DH-PH unit, SOS1 in a complex with EPS8 and ABI1 (E3B1) also acts as a context-dependent exchange factor for RAC1, coupling Ras and Rac signalling. SOS1 contributes to multivalent pLAT-GRB2-SOS1 condensates in T cell receptor signalling. Heterozygous gain-of-function SOS1 variants, clustered in autoinhibitory interfaces, cause Noonan syndrome 4, and a C-terminal frameshift truncating the proline-rich region causes hereditary gingival fibromatosis 1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002931 response to ischemia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA response to ischemia transferred from rat Sos1 (D4A3T0) via Ensembl Compara; the rat source is an IDA from an ischemia model. Reason: Changes in SOS1 levels or activity after ischemia are a context-specific response, not a function of SOS1. The molecular role of SOS1 is Ras nucleotide exchange downstream of receptors; 'response to ischemia' adds no information about what SOS1 does and is an over-annotation for the human protein. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0005085 guanyl-nucleotide exchange factor activity | EXP PMID:1371879 p21ras activation via hemopoietin receptors and c-kit requir... | ACCEPT | Summary: EXP guanyl-nucleotide exchange factor activity citing a 1992 study of p21ras activation by hemopoietin receptors and c-kit. Reason: The function is correct and core (SOS1 Ras-GEF activity is directly demonstrated by PMID:8493579). The cited abstract reports receptor-induced Ras activation without naming SOS1, so it appears to be a pathway-context reference; accepting on the strength of the function while noting the reference does not itself assay SOS1 in its abstract. Supporting Evidence: PMID:1371879 resulted in activation of p21ras in various hemopoietic cell lines PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | EXP PMID:16483568 Stem cell factor and its receptor c-Kit as targets for infla... | ACCEPT | Summary: EXP guanyl-nucleotide exchange factor activity citing a 2006 review of SCF/c-Kit as an inflammatory-disease target. Reason: The function is correct and core. The cited paper is a review on SCF/c-Kit that does not assay SOS1 exchange activity (likely a pathway-context citation for the KIT-GRB2-SOS-Ras step); the annotation is accepted on the basis of direct evidence elsewhere, and the reference is flagged in reference_review. Supporting Evidence: PMID:16483568 Binding of SCF to c-Kit leads to activation of multiple pathways PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. |
| GO:0005085 guanyl-nucleotide exchange factor activity | EXP PMID:7731718 The motogenic and mitogenic responses to HGF are amplified b... | ACCEPT | Summary: EXP guanyl-nucleotide exchange factor activity citing a study of SHC as an amplifier of HGF receptor (MET) signalling. Reason: The function is correct and core. The abstract describes MET-SHC-GRB2 coupling to Ras rather than a SOS1 exchange assay, so it appears to be a pathway-context reference (Reactome MET events); accepting on the function. Supporting Evidence: PMID:7731718 HGF stimulation can trigger the Ras pathway by recruiting Grb2 both directly through the receptor, and indirectly, through Shc. PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA guanyl-nucleotide exchange factor activity from PAINT node PTN000560991 (PTHR23113 RasGEF family), whose experimental donors include RasGEFs from yeast, Dictyostelium, worm, fly and mammals, including SOS1 itself. Reason: Core molecular function. SOS1 has an intact REM plus CDC25-homology catalytic module and lies inside the clade to which PAINT assigned GEF activity. SOS1's own experimental annotation is one of the descendant evidences, which is expected rather than circular. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IDA PMID:8479536 Association of Sos Ras exchange protein with Grb2 is implica... | ACCEPT | Summary: IDA guanyl-nucleotide exchange factor activity from the 1993 study linking Sos to Grb2 in tyrosine-kinase signalling. Reason: Core molecular function. The abstract describes murine Sos1 as a Ras exchange factor bound by Grb2 SH3 domains; deferring to the curator on what was assayed in the full text, the function is well established for human SOS1. Supporting Evidence: PMID:8479536 Grb2-Sem-5 binds directly to murine Sos1, a Ras exchange factor, through two SH3 domains. PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA guanyl-nucleotide exchange factor activity from combined InterPro (RasGEF/DH) and ortholog evidence. Reason: Correct; duplicate of the IBA and experimental core MF. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS PMID:8493579 Human Sos1: a guanine nucleotide exchange factor for Ras tha... | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from the paper that cloned hSos1 and showed its CDC25 domain stimulates exchange on Ras. Reason: Core molecular function, directly demonstrated in this paper (in vitro exchange, yeast CDC25 complementation, cellular overexpression). Supporting Evidence: PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS PMID:9790532 Crystal structure of the Dbl and pleckstrin homology domains... | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from the crystal structure of the SOS1 DH-PH module. Reason: GEF activity is correct for SOS1. This paper concerns the DH-PH unit, which in other Dbl-family proteins is a Rho-family GEF module; for SOS1 it supports the secondary, context-dependent Rac-GEF function (PMID:9438849, PMID:11777939), which is also covered by GO:0005085. Supporting Evidence: PMID:9790532 Proteins containing Dbl homology (DH) domains activate Rho-family GTPases by functioning as specific guanine nucleotide exchange factors. PMID:9438849 the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-177938 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-177938 ('SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-177938 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1) PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-177945 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-177945 ('SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-177945 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1) PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-186834 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-186834 ('SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-186834 SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS) PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-210977 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-210977 ('Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos)'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-210977 Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos) PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-2424477 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-2424477 ('SOS mediated nucleotide exchange of RAS (SHC)'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-2424477 SOS mediated nucleotide exchange of RAS (SHC) PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-392054 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-392054 ('NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-392054 NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-9607304 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-9607304 ('SOS1-mediated nucleotide exchange of RAS downstream of FLT3'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-9607304 SOS1-mediated nucleotide exchange of RAS downstream of FLT3 PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-9670436 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-9670436 ('p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-9670436 p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-9672170 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-9672170 ('SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-9672170 SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-9695853 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-9695853 ('FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-9695853 FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-9703441 | ACCEPT | Summary: TAS guanyl-nucleotide exchange factor activity from Reactome event Reactome:R-HSA-9703441 ('SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants'). Reason: Core molecular function. In this event receptor-bound GRB2:SOS1 catalyses GDP release from RAS and GTP loading, which is the canonical SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-9703441 SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants PMID:8493579 Thus hSos1 is a guanine nucleotide exchange factor for Ras. |
| GO:0005096 GTPase activator activity | TAS PMID:9790532 Crystal structure of the Dbl and pleckstrin homology domains... | MODIFY | Summary: TAS GTPase activator activity from the SOS1 DH-PH crystal structure paper. Reason: GO:0005096 GTPase activator activity describes GAP-type stimulation of GTP hydrolysis, which SOS1 does not perform. The DH domain activates Rho-family GTPases as a nucleotide exchange factor, so the correct MF is GO:0005085 guanyl-nucleotide exchange factor activity. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:9790532 Proteins containing Dbl homology (DH) domains activate Rho-family GTPases by functioning as specific guanine nucleotide exchange factors. PMID:9438849 the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA epidermal growth factor receptor binding transferred from rat Sos1 (D4A3T0), whose source is an IPI. Reason: SOS1 associates with activated EGFR through GRB2 (and SHC1-GRB2), which binds receptor phosphotyrosines with its SH2 domain and SOS1 with its SH3 domains. SOS1 has no receptor-binding domain, so a direct EGFR-binding MF over-interprets co-precipitation; the relevant SOS1 function is SH3 domain binding. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. |
| GO:0005515 protein binding | IPI PMID:10026169 Identification of Grb4/Nckbeta, a src homology 2 and 3 domai... | MODIFY | Summary: IPI for SOS1 binding NCK2, from a study identifying the Nck paralog Grb4/Nckbeta and its SH3-mediated associations. NCK2 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:10026169 Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2 PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:10026169 Identification of Grb4/Nckbeta, a src homology 2 and 3 domai... | MODIFY | Summary: IPI for SOS1 binding NCK1, from a study identifying the Nck paralog Grb4/Nckbeta and its SH3-mediated associations. NCK1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:10026169 Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2 PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:10206341 Characterization of interactions of Nck with Sos and dynamin... | MODIFY | Summary: IPI for SOS1 binding NCK1, from a GST pull-down study mapping the Nck-Sos interaction to the third Nck SH3 domain. NCK1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:10206341 We found that exclusively the third (C-terminal) SH3 domain of Nck has the ability to bind to Sos. PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:12029088 Identification of novel SH3 domain ligands for the Src famil... | MODIFY | Summary: IPI for SOS1 binding HCK, from a mass-spectrometry screen for ligands of the HCK SH3 domain. HCK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. HCK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:12029088 we used mass spectrometry to identify approximately 25 potential binding partners for the SH3 domain of Hck PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:12482578 Interaction of nebulin SH3 domain with titin PEVK and myopal... | MODIFY | Summary: IPI for SOS1 binding NEB (nebulin), from a biophysical study of nebulin SH3 domain binding to proline-rich peptides. NEB (nebulin) is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NEB (nebulin) binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:12482578 We have investigated the binding of nebulin SH3 with proline-rich peptides PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei... | MODIFY | Summary: IPI for SOS1 binding GRB2, from a SILAC screen of proteins retrieved on the GRB2 SH2 domain after EGF stimulation. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:12577067 Combined cell lysates were affinity-purified over the SH2 domain of the adapter protein Grb2 PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:12628188 Structural evidence for feedback activation by Ras.GTP of th... | MODIFY | Summary: IPI for SOS1 binding HRAS, from crystallographic and solution studies revealing the distal Ras-GTP allosteric site of SOS. Besides its catalytic site, SOS1 binds Ras (preferentially Ras-GTP) at a distal allosteric site in the REM domain, which relieves autoinhibition and creates positive feedback. Reason: GO:0005515 'protein binding' is uninformative. The paper characterises binding of Ras to the allosteric site of SOS1, a regulatory binding event distinct from substrate turnover; GO:0031267 small GTPase binding is the informative MF for SOS1 in this interaction (the reciprocal HRAS activity is modelled on HRAS). Proposed replacements: small GTPase binding Supporting Evidence: PMID:12628188 Ras.GTP forms ternary complexes with SOS(cat) in solution and increases significantly the rate of SOS(cat)-stimulated nucleotide release from Ras PMID:12628188 a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP |
| GO:0005515 protein binding | IPI PMID:14679214 A novel proteomic screen for peptide-protein interactions. | MODIFY | Summary: IPI for SOS1 binding GRB2, from a SILAC peptide pull-down screen in which a SOS proline-rich peptide retrieved only SH3-domain proteins. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:14679214 A novel proteomic screen for peptide-protein interactions. | MODIFY | Summary: IPI for SOS1 binding PACSIN3, from a SILAC peptide pull-down screen in which a SOS proline-rich peptide retrieved only SH3-domain proteins. PACSIN3 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. PACSIN3 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:14679214 A novel proteomic screen for peptide-protein interactions. | MODIFY | Summary: IPI for SOS1 binding SNX9, from a SILAC peptide pull-down screen in which a SOS proline-rich peptide retrieved only SH3-domain proteins. SNX9 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. SNX9 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:15507210 Structural analysis of autoinhibition in the Ras activator S... | MODIFY | Summary: IPI for SOS1 binding HRAS, from crystallographic/biochemical analysis of DH-PH-mediated autoinhibition of the SOS allosteric Ras site. Besides its catalytic site, SOS1 binds Ras (preferentially Ras-GTP) at a distal allosteric site in the REM domain, which relieves autoinhibition and creates positive feedback. Reason: GO:0005515 'protein binding' is uninformative. The paper characterises binding of Ras to the allosteric site of SOS1, a regulatory binding event distinct from substrate turnover; GO:0031267 small GTPase binding is the informative MF for SOS1 in this interaction (the reciprocal HRAS activity is modelled on HRAS). Proposed replacements: small GTPase binding Supporting Evidence: PMID:15507210 the DH-PH unit blocks the allosteric binding site for Ras and suppresses the activity of SOS PMID:12628188 a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP |
| GO:0005515 protein binding | IPI PMID:16520382 Sos-mediated activation of rac1 by p66shc. | MODIFY | Summary: IPI for SOS1 binding GRB2, from a focused study of p66shc-driven switching of SOS1 from GRB2 to the EPS8-E3B1 Rac-GEF complex. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:16520382 The proline-rich COOH-terminal region of sos1 (C-sos1) binds to the src homology (SH) 3 domains of the adaptor protein growth factor receptor bound protein (grb2). PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:17084389 Catalytic competence of the Ras-GEF domain of hSos1 requires... | MODIFY | Summary: IPI for SOS1 binding HRAS, from a mutational study of intra-REM interactions needed for catalytic competence of hSos1. Here HRAS is engaged at the SOS1 CDC25-homology catalytic site as the exchange substrate. Reason: GO:0005515 'protein binding' is uninformative. The interaction characterised in this paper is the enzyme-substrate engagement of Ras by the SOS1 catalytic domain, which is what GO:0005085 guanyl-nucleotide exchange factor activity describes; that is the informative MF supported by the paper. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:17084389 the catalytic core (residues 742-1024) contains all residues binding to Ras, including the catalytic hairpin PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. |
| GO:0005515 protein binding | IPI PMID:17141806 Solution structure of a Hck SH3 domain ligand complex reveal... | MODIFY | Summary: IPI for SOS1 binding HCK, from an NMR study of the HCK SH3 domain bound to a proline-rich ligand. HCK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. HCK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17141806 We studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MODIFY | Summary: IPI for SOS1 binding NCK1, from a peptide-array screen of SH3 domains (SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) against proline-rich ligands. NCK1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MODIFY | Summary: IPI for SOS1 binding PLCG1, from a peptide-array screen of SH3 domains (SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) against proline-rich ligands. PLCG1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. PLCG1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MODIFY | Summary: IPI for SOS1 binding PIK3R1 (p85alpha), from a peptide-array screen of SH3 domains (SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) against proline-rich ligands. PIK3R1 (p85alpha) is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. PIK3R1 (p85alpha) binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MODIFY | Summary: IPI for SOS1 binding CRK, from a peptide-array screen of SH3 domains (SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) against proline-rich ligands. CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MODIFY | Summary: IPI for SOS1 binding GRB2, from a peptide-array screen of SH3 domains (SRC, PLCG1, P85A, NCK1, GRB2, FYN, CRK) against proline-rich ligands. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:17515907 Structural basis for the transforming activity of human canc... | MODIFY | Summary: IPI for SOS1 binding CRK, from an NMR structural study of the CRK adaptor (CRKI/CRKII). CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:18454158 Membrane-dependent signal integration by the Ras activator S... | MODIFY | Summary: IPI for SOS1 binding HRAS, from reconstituted-membrane kinetics of Ras activation by SOS, showing allosteric-site anchoring. Besides its catalytic site, SOS1 binds Ras (preferentially Ras-GTP) at a distal allosteric site in the REM domain, which relieves autoinhibition and creates positive feedback. Reason: GO:0005515 'protein binding' is uninformative. The paper characterises binding of Ras to the allosteric site of SOS1, a regulatory binding event distinct from substrate turnover; GO:0031267 small GTPase binding is the informative MF for SOS1 in this interaction (the reciprocal HRAS activity is modelled on HRAS). Proposed replacements: small GTPase binding Supporting Evidence: PMID:18454158 SOS has two binding sites for Ras, one of which is an allosteric site that is distal to the active site. PMID:12628188 a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP |
| GO:0005515 protein binding | IPI PMID:19141281 Differences in flexibility underlie functional differences i... | MODIFY | Summary: IPI for SOS1 binding HRAS, from a mutational and molecular-dynamics study of allosteric activation of SOS by Ras. Besides its catalytic site, SOS1 binds Ras (preferentially Ras-GTP) at a distal allosteric site in the REM domain, which relieves autoinhibition and creates positive feedback. Reason: GO:0005515 'protein binding' is uninformative. The paper characterises binding of Ras to the allosteric site of SOS1, a regulatory binding event distinct from substrate turnover; GO:0031267 small GTPase binding is the informative MF for SOS1 in this interaction (the reciprocal HRAS activity is modelled on HRAS). Proposed replacements: small GTPase binding Supporting Evidence: PMID:19141281 The Ras-specific nucleotide exchange factor Son of sevenless (Sos) is inactive without Ras bound to a distal allosteric site. PMID:12628188 a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP |
| GO:0005515 protein binding | IPI PMID:19323566 SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within t... | MODIFY | Summary: IPI for SOS1 binding GRB2, from an ITC study of GRB2 nSH3/cSH3 binding to the four PXpsiPXR sites of SOS1. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:19323566 the Grb2-Sos1 interaction is mediated through the combinatorial binding of nSH3 and cSH3 domains of Grb2 to various sites containing PXpsiPXR motifs within Sos1 PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | REMOVE | Summary: IPI for SOS1 association with SHC1, from TAP/MS charting of the Bcr-Abl interaction network. SOS1 has no phosphotyrosine-binding domain; it associates with SHC1 indirectly, through GRB2 bound to receptor or SHC1 phosphotyrosines. Reason: GO:0005515 'protein binding' is uninformative, and the association is bridged by GRB2 rather than a direct SOS1 binding function, so no more specific MF can be assigned to SOS1 from it. Removal does not mean the SOS1-SHC1 co-complex is false; the GRB2-mediated recruitment is captured by GO:0017124 SH3 domain binding. Supporting Evidence: PMID:19380743 The resulting network revealed a high degree of interconnection of 7 "core" components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2) file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | MODIFY | Summary: IPI for SOS1 binding CRK, from TAP/MS charting of the Bcr-Abl interaction network. CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:19380743 The resulting network revealed a high degree of interconnection of 7 "core" components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2) PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:19464300 Isoform-selective interaction of the adaptor protein Tks5/FI... | MODIFY | Summary: IPI for SOS1 binding SH3PXD2A/Tks5 (isoform 2), from a focused study identifying SOS1 as a partner of the tandem SH3A-SH3B domains of Tks5. SH3PXD2A/Tks5 (isoform 2) is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. SH3PXD2A/Tks5 (isoform 2) binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:19464300 both intact SH3 domains are required for efficient binding to the entire proline-rich domain of Sos1 PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:20133692 Role of the histone domain in the autoinhibition and activat... | MODIFY | Summary: IPI for SOS1 binding HRAS, from a crystal structure of SOS including the histone domain, with kinetics of Noonan mutants on membrane Ras. Besides its catalytic site, SOS1 binds Ras (preferentially Ras-GTP) at a distal allosteric site in the REM domain, which relieves autoinhibition and creates positive feedback. Reason: GO:0005515 'protein binding' is uninformative. The paper characterises binding of Ras to the allosteric site of SOS1, a regulatory binding event distinct from substrate turnover; GO:0031267 small GTPase binding is the informative MF for SOS1 in this interaction (the reciprocal HRAS activity is modelled on HRAS). Proposed replacements: small GTPase binding Supporting Evidence: PMID:20133692 SOS is inactive unless Ras is bound to an allosteric site on SOS PMID:12628188 a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | REMOVE | Summary: IPI for SOS1 association with EGFR, from co-immunoprecipitation of the EGFRvIII signalosome in glioblastoma cells. SOS1 has no phosphotyrosine-binding domain; it associates with EGFR indirectly, through GRB2 bound to receptor or SHC1 phosphotyrosines. Reason: GO:0005515 'protein binding' is uninformative, and the association is bridged by GRB2 rather than a direct SOS1 binding function, so no more specific MF can be assigned to SOS1 from it. Removal does not mean the SOS1-EGFR co-complex is false; the GRB2-mediated recruitment is captured by GO:0017124 SH3 domain binding. Supporting Evidence: PMID:20473329 We observed reduced EGFRvIII/SHP-2/Gab1/Grb2/Sos-1 interaction file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | MODIFY | Summary: IPI for SOS1 binding GRB2, from co-immunoprecipitation of the EGFRvIII signalosome in glioblastoma cells. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:20473329 We observed reduced EGFRvIII/SHP-2/Gab1/Grb2/Sos-1 interaction PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d... | MODIFY | Summary: IPI for SOS1 binding GRB2, from AP-SRM quantification of GRB2 complexes after growth-factor stimulation. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:21706016 comprehensively and quantitatively investigate changes in protein interactions with GRB2 PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MODIFY | Summary: IPI for SOS1 binding GRB2, from a human liver proteome-scale yeast two-hybrid network. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:23397142 Analysis of protein-protein interactions in cross-talk pathw... | MODIFY | Summary: IPI for SOS1 binding HCK, from in situ proximity ligation profiling of cross-talk interactions in hepatocellular carcinoma cells. HCK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. HCK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:23397142 we found that HCK had several novel interaction partners, including CRKL, FLT1, EGFR, SOS1, PLCG1, and PIK3CB PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: IPI for SOS1 binding PIK3R1 (p85alpha), from in situ proximity ligation profiling of endogenous interactions in HeLa cells. PIK3R1 (p85alpha) is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. PIK3R1 (p85alpha) binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: IPI for SOS1 binding CRK, from in situ proximity ligation profiling of endogenous interactions in HeLa cells. CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:26005835 RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and rest... | REMOVE | Summary: IPI for SOS1 association with EGFR, from a study of opposing EGFR-SOS1-Ras and RasGRP1 signals in intestinal epithelium. SOS1 has no phosphotyrosine-binding domain; it associates with EGFR indirectly, through GRB2 bound to receptor or SHC1 phosphotyrosines. Reason: GO:0005515 'protein binding' is uninformative, and the association is bridged by GRB2 rather than a direct SOS1 binding function, so no more specific MF can be assigned to SOS1 from it. Removal does not mean the SOS1-EGFR co-complex is false; the GRB2-mediated recruitment is captured by GO:0017124 SH3 domain binding. Supporting Evidence: PMID:26005835 RasGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-Ras signals in CRC cells file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI for SOS1 binding GRB2, from the BioPlex 2.0 AP-MS interactome. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:30631038 The CSN3 subunit of the COP9 signalosome interacts with the ... | REMOVE | Summary: IPI for SOS1 binding COPS3 (CSN3), from a yeast two-hybrid and pull-down study mapping CSN3 binding to the SOS1 histone-fold (HD) region; the interaction was reported to regulate SOS1 protein stability. Reason: GO:0005515 'protein binding' is uninformative and no specific molecular function of SOS1 is established by this interaction (SOS1 is the regulated partner). Removal does not imply the interaction is false. Supporting Evidence: PMID:30631038 we identified the interaction between the Sos1 HD region and CSN3, the third component of the COP9 signalosome |
| GO:0005515 protein binding | IPI PMID:31820037 Elucidation of protein interactions necessary for the mainte... | MODIFY | Summary: IPI for SOS1 binding GRB2, from a study of the BCR-ABL core signalling complex in CML cells. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:31820037 core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2 PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI for SOS1 binding CRK, from AP-MS rewiring analysis of the EGFR network in KRAS(G13D) colorectal cancer cells. CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: IPI for SOS1 binding GRB2, from AP-MS rewiring analysis of the EGFR network in KRAS(G13D) colorectal cancer cells. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI for SOS1 binding UBASH3A/STS-2 (isoform 2), from the HuRI reference binary (yeast two-hybrid) interactome. UBASH3A/STS-2 (isoform 2) is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. UBASH3A/STS-2 (isoform 2) binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI for SOS1 binding NCK1, from the BioPlex 3.0 AP-MS interactome. NCK1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI for SOS1 binding CRK, from the BioPlex 3.0 AP-MS interactome. CRK is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. CRK binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI for SOS1 binding GRB2, from the BioPlex 3.0 AP-MS interactome. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | REMOVE | Summary: IPI for SOS1 association with EGFR, from a head and neck cancer AP-MS protein network map. SOS1 has no phosphotyrosine-binding domain; it associates with EGFR indirectly, through GRB2 bound to receptor or SHC1 phosphotyrosines. Reason: GO:0005515 'protein binding' is uninformative, and the association is bridged by GRB2 rather than a direct SOS1 binding function, so no more specific MF can be assigned to SOS1 from it. Removal does not mean the SOS1-EGFR co-complex is false; the GRB2-mediated recruitment is captured by GO:0017124 SH3 domain binding. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI for SOS1 binding NCK1, from multimodal (AP-MS plus imaging) human cell maps. NCK1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. NCK1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI for SOS1 binding GRB2, from multimodal (AP-MS plus imaging) human cell maps. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:7527391 Independent binding of peptide ligands to the SH2 and SH3 do... | MODIFY | Summary: IPI for SOS1 binding GRB2, from an ITC/SPR study of peptide binding to the GRB2 SH2 and SH3 domains, using a SOS proline-rich peptide. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:7527391 via its SH3 domains with proline-rich sequences in the Ras guanine nucleotide releasing factor, Son of sevenless (Sos) PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:7629138 Differential interactions of human Sos1 and Sos2 with Grb2. | MODIFY | Summary: IPI for SOS1 binding GRB2, from a focused comparison of human Sos1 and Sos2 binding to Grb2. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:7629138 In general, these characteristics are similar to the ones reported previously for the interaction of hSos1 with Grb2. PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:7773779 NMR structure of the N-terminal SH3 domain of GRB2 and its c... | MODIFY | Summary: IPI for SOS1 binding GRB2, from the NMR structure of the GRB2 N-terminal SH3 domain bound to a SOS proline-rich peptide. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:7773779 GRB2 couples receptor tyrosine kinase activation to Ras signalling by interacting, through its SH3 domains, to the carboxy-terminal proline-rich regions of the guanine nucleotide exchange factor Sos. PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:9020117 Subsets of epidermal growth factor receptors during activati... | MODIFY | Summary: IPI for SOS1 binding PLCG1, from a study of Tyr992-phosphorylated EGFR subpopulations and their associated signalling proteins. PLCG1 is an SH3-domain protein, and SOS1 engages SH3 domains through its C-terminal proline-rich region. Reason: GO:0005515 'protein binding' is uninformative. PLCG1 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:9020117 Tyr(P)992 receptors were associated with more SOS, Ras-GTPase activating protein, phosphatidylinositol 3-kinase, and SHPTP2/syp, but less Grb2 PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0005515 protein binding | IPI PMID:9447984 Regulation of Sos activity by intramolecular interactions. | MODIFY | Summary: IPI for SOS1 binding HRAS, from a truncation-mutant study of intramolecular autoinhibition of hSos1. Here HRAS is engaged at the SOS1 CDC25-homology catalytic site as the exchange substrate. Reason: GO:0005515 'protein binding' is uninformative. The interaction characterised in this paper is the enzyme-substrate engagement of Ras by the SOS1 catalytic domain, which is what GO:0005085 guanyl-nucleotide exchange factor activity describes; that is the informative MF supported by the paper. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:9447984 in vitro Ras binding experiments suggest that the amino and carboxyl terminus domains exert negative allosteric control on the interaction of the Sos catalytic domain with Ras PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. |
| GO:0005515 protein binding | IPI PMID:9447984 Regulation of Sos activity by intramolecular interactions. | MODIFY | Summary: IPI for SOS1 binding GRB2, from a truncation-mutant study of intramolecular autoinhibition of hSos1. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:9447984 in vitro Ras binding experiments suggest that the amino and carboxyl terminus domains exert negative allosteric control on the interaction of the Sos catalytic domain with Ras PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:9544989 Shc phosphotyrosine-binding domain dominantly interacts with... | REMOVE | Summary: IPI for SOS1 association with SHC1, from a study of SHC PTB/SH2 domain binding to EGFR and downstream GRB2-SOS association. SOS1 has no phosphotyrosine-binding domain; it associates with SHC1 indirectly, through GRB2 bound to receptor or SHC1 phosphotyrosines. Reason: GO:0005515 'protein binding' is uninformative, and the association is bridged by GRB2 rather than a direct SOS1 binding function, so no more specific MF can be assigned to SOS1 from it. Removal does not mean the SOS1-SHC1 co-complex is false; the GRB2-mediated recruitment is captured by GO:0017124 SH3 domain binding. Supporting Evidence: PMID:9544989 was tyrosine-phosphorylated, and associated with Grb2 and Sos file:human/SOS1/SOS1-deep-research-falcon.md Following receptor tyrosine-kinase activation, GRB2’s SH2 domain recognizes receptor-associated phosphotyrosine sites while its SH3 domains bind PXXP motifs in the SOS1 C-terminal tail. |
| GO:0005515 protein binding | IPI PMID:9569023 Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2. | MODIFY | Summary: IPI for SOS1 binding GRB2, from a study showing Dab2 competes with Sos for the SH3 domains of Grb2. GRB2 recruits SOS1 to phosphotyrosine sites on activated receptors by binding PXXP motifs of the SOS1 proline-rich tail with its SH3 domains; this is the defining SOS-GRB2 coupling. Reason: GO:0005515 'protein binding' is uninformative. GRB2 binds through its SH3 domain(s) to the proline-rich C-terminal tail of SOS1 (the region that couples SOS1 to GRB2 and other SH3 adaptors), so GO:0017124 SH3 domain binding captures the molecular basis of the interaction, consistent with the SOS2 review. Deferring to the curator on the interaction itself. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:9569023 The proline-rich sequences of Sos mediate the interaction of Sos with Grb2, an adaptor protein which coupled tyrosine kinase receptors to Sos. PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. |
| GO:0005515 protein binding | IPI PMID:9690470 The structural basis of the activation of Ras by Sos. | MODIFY | Summary: IPI for SOS1 binding HRAS, from the crystal structure of H-Ras bound to the SOS catalytic region. Here HRAS is engaged at the SOS1 CDC25-homology catalytic site as the exchange substrate. Reason: GO:0005515 'protein binding' is uninformative. The interaction characterised in this paper is the enzyme-substrate engagement of Ras by the SOS1 catalytic domain, which is what GO:0005085 guanyl-nucleotide exchange factor activity describes; that is the informative MF supported by the paper. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:9690470 The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. PMID:8493579 This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. |
| GO:0005737 cytoplasm | IDA PMID:17515907 Structural basis for the transforming activity of human canc... | ACCEPT | Summary: IDA cytoplasm from a structural study of the CRK adaptor. Reason: SOS1 is a soluble cytoplasmic (cytosolic) protein; correct though less specific than cytosol. Deferring to the curator on the full-text evidence. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: IEA cytosol from an ARBA machine-learning rule. Reason: SOS1 is cytosolic in unstimulated cells before GRB2-mediated recruitment to receptor complexes. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109813 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-109813 ('GRB2-1 binds SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-109813 GRB2-1 binds SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109822 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-109822 ('MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1'), an ERK-feedback event in which phosphorylated SOS1 dissociates from, or is phosphorylated within, GRB2 complexes. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-109822 MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109823 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-109823 ('MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y-IRS1,p-Y-IRS2'), an ERK-feedback event in which phosphorylated SOS1 dissociates from, or is phosphorylated within, GRB2 complexes. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-109823 MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y-IRS1,p-Y-IRS2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225950 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1225950 ('Binding of GRB2:SOS1 complex to phosphorylated ligand-responsive EGFR mutants'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1225950 Binding of GRB2:SOS1 complex to phosphorylated ligand-responsive EGFR mutants file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225951 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1225951 ('SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1225951 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225957 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1225957 ('SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1225957 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225961 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1225961 ('Phosphorylated SHC1 in complex with ligand-responsive p-6Y-EGFR mutants recruits GRB2:SOS1 complex'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1225961 Phosphorylated SHC1 in complex with ligand-responsive p-6Y-EGFR mutants recruits GRB2:SOS1 complex file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250380 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1250380 ('Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250383 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1250383 ('RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1306969 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1306969 ('GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1306972 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1306972 ('RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433471 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-1433471 ('Activation of RAS by p-KIT bound SOS1'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-1433471 Activation of RAS by p-KIT bound SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177936 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-177936 ('GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-177936 GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177938 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-177938 ('SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-177938 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177943 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-177943 ('GRB2:SOS1 complex binds to EGF:EGFR complex'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-177943 GRB2:SOS1 complex binds to EGF:EGFR complex file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177945 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-177945 ('SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-177945 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-186826 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-186826 ('GRB2:SOS1 complex binds to the active receptor'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-186826 GRB2:SOS1 complex binds to the active receptor file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-186834 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-186834 ('SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-186834 SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205039 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-205039 ('p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-205039 p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205244 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-205244 ('Recruitment of CBL to KIT'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-205244 Recruitment of CBL to KIT file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205286 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-205286 ('GRB2:SOS interacts with p-KIT'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-205286 GRB2:SOS interacts with p-KIT file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-210974 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-210974 ('Interaction of SOS-1 to Tie2 bound Grb2'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-210974 Interaction of SOS-1 to Tie2 bound Grb2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-210977 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-210977 ('Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-210977 Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2179407 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2179407 ('SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-2179407 SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2179415 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2179415 ('GRB2:SOS1 binds to HBEGF:p-Y-EGFR'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-2179415 GRB2:SOS1 binds to HBEGF:p-Y-EGFR file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396561 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2396561 ('Recruitment of GADS:SLP-76 to p-5Y-LAT'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2396561 Recruitment of GADS:SLP-76 to p-5Y-LAT file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396594 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2396594 ('Phosphorylation of SLP-76 by p-SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2396594 Phosphorylation of SLP-76 by p-SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396599 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2396599 ('Recruitment of GRB2:SOS to p-5Y-LAT'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-2396599 Recruitment of GRB2:SOS to p-5Y-LAT file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396606 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2396606 ('Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2396606 Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424476 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424476 ('Activation of RAC1 by VAV2/3'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-2424476 Activation of RAC1 by VAV2/3 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424477 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424477 ('SOS mediated nucleotide exchange of RAS (SHC)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-2424477 SOS mediated nucleotide exchange of RAS (SHC) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424481 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424481 ('Recruitment of VAV and BTK to p-SLP-76'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2424481 Recruitment of VAV and BTK to p-SLP-76 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424484 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424484 ('Phosphorylation of BTK by p-SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2424484 Phosphorylation of BTK by p-SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424485 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424485 ('Release of p-PLCG1'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2424485 Release of p-PLCG1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424486 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424486 ('Phosphorylation and activation of VAV2/VAV3 by SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2424486 Phosphorylation and activation of VAV2/VAV3 by SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424487 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2424487 ('Phosphorylation of PLC-gamma by p-BTK/p-SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2424487 Phosphorylation of PLC-gamma by p-BTK/p-SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730833 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730833 ('Phosphorylation of TEC kinases by p-SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730837 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730837 ('Recruitment of GRB2:SOS to p-10Y-NTAL'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-2730837 Recruitment of GRB2:SOS to p-10Y-NTAL file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730840 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730840 ('Activation of RAC1 by VAV'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-2730840 Activation of RAC1 by VAV file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730841 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730841 ('Phosphorylation and activation of VAV'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730841 Phosphorylation and activation of VAV file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730842 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730842 ('PI3K associates with phosphorylated GAB2'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730842 PI3K associates with phosphorylated GAB2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730844 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730844 ('Interaction of GRB2:SOS complex with p-SHC1'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-2730844 Interaction of GRB2:SOS complex with p-SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730847 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730847 ('Hydrolysis of PIP2 by PLCG'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730847 Hydrolysis of PIP2 by PLCG file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730851 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730851 ('Phosphorylation of SLP-76 by p-SYK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730851 Phosphorylation of SLP-76 by p-SYK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730856 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730856 ('Autophosphorylation of PAK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730856 Autophosphorylation of PAK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730858 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730858 ('Autophosphorylation of BTK/ITK'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730858 Autophosphorylation of BTK/ITK file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730870 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730870 ('Phosphorylation of PIP2 to PIP3 by PI3K'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730870 Phosphorylation of PIP2 to PIP3 by PI3K file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730889 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730889 ('Recruitment of PAK to the membrane by binding active RAC1'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730892 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-2730892 ('Recruitment of VAV to p-SLP-76'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-2730892 Recruitment of VAV to p-SLP-76 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354165 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-354165 ('Interaction of SOS with GRB2 bound to FADK1'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-354165 Interaction of SOS with GRB2 bound to FADK1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392053 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-392053 ('SOS binds Grb2 bound to pFAK:NCAM1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-392053 SOS binds Grb2 bound to pFAK:NCAM1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392054 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-392054 ('NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-392054 NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-419166 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-419166 ('GEFs activate RhoA,B,C'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-419166 GEFs activate RhoA,B,C file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-453111 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-453111 ('Phosphorylated SHC recruits GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-453111 Phosphorylated SHC recruits GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637770 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5637770 ('Binding of GRB2:SOS1 complex to phosphorylated EGFRvIII'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5637770 Binding of GRB2:SOS1 complex to phosphorylated EGFRvIII file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637798 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5637798 ('Phosphorylated SHC1 in complex with p-5Y-EGFRvIII recruits GRB2:SOS1 complex'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5637798 Phosphorylated SHC1 in complex with p-5Y-EGFRvIII recruits GRB2:SOS1 complex file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637806 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5637806 ('SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFRvIII)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5637806 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFRvIII) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637808 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5637808 ('SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII)'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5637808 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654392 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654392 ('Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654392 Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654402 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654402 ('Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654402 Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654406 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654406 ('Activated FGFR2:p-SHC1 binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654406 Activated FGFR2:p-SHC1 binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654413 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654413 ('Activated FGFR3:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654413 Activated FGFR3:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654416 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654416 ('Activated FGFR3:pFRS binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654416 Activated FGFR3:pFRS binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654423 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654423 ('Activated FGFR4:p-SHC1 binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654423 Activated FGFR4:p-SHC1 binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654426 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654426 ('Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654426 Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654586 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654586 ('Activated FGFR1:p-FRS binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654586 Activated FGFR1:p-FRS binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654597 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654597 ('Activated FGFR1:p-SHC1 binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654597 Activated FGFR1:p-SHC1 binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654600 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654600 ('Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654600 Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654615 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654615 ('Activated FGFR2:pFRS binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654615 Activated FGFR2:pFRS binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654618 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654618 ('Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654618 Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654646 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654646 ('Activated FGFR3:p-SHC1 binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654646 Activated FGFR3:p-SHC1 binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654647 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654647 ('Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654647 Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654663 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654663 ('Activated FGFR4:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654663 Activated FGFR4:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654664 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5654664 ('Activated FGFR4:p-FRS binds GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5654664 Activated FGFR4:p-FRS binds GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655233 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655233 ('Activated FGFR2 mutants:p-FRS2 binds GRB2-SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655233 Activated FGFR2 mutants:p-FRS2 binds GRB2-SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655241 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655241 ('Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655241 Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655266 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655266 ('Activated FGFR1 mutants:p-FRS2 binds GRB2-SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655266 Activated FGFR1 mutants:p-FRS2 binds GRB2-SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655277 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655277 ('Activated FGFR3 point, translocation and fusion mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655277 Activated FGFR3 point, translocation and fusion mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655295 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655295 ('Activated FGFR3 point, translocation and fusion mutants:p-FRS2 binds GRB2-SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655295 Activated FGFR3 point, translocation and fusion mutants:p-FRS2 binds GRB2-SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655326 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655326 ('Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655326 Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655347 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655347 ('Activated FGFR4 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655347 Activated FGFR4 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5655348 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5655348 ('Activated FGFR4 mutants:p-FRS2 binds GRB2-SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5655348 Activated FGFR4 mutants:p-FRS2 binds GRB2-SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5672965 ('RAS GEFs promote RAS nucleotide exchange'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5685366 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5685366 ('GRB2-1:SOS1 binds p-Y-SHC'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5685366 GRB2-1:SOS1 binds p-Y-SHC file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686073 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5686073 ('GRB2-1:SOS1 binds p-3Y-SHC1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5686073 GRB2-1:SOS1 binds p-3Y-SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686074 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5686074 ('GRB2-1:p-4S-SOS1:p-Y427-SHC1 dissociates'), an ERK-feedback event in which phosphorylated SOS1 dissociates from, or is phosphorylated within, GRB2 complexes. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5686074 GRB2-1:p-4S-SOS1:p-Y427-SHC1 dissociates file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686315 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-5686315 ('GRB2:p-4S-SOS1:p-Y-IRS1,p-Y-IRS2 dissociates'), an ERK-feedback event in which phosphorylated SOS1 dissociates from, or is phosphorylated within, GRB2 complexes. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-5686315 GRB2:p-4S-SOS1:p-Y-IRS1,p-Y-IRS2 dissociates file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74736 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-74736 ('GRB2-1:SOS1 binds p-IRS1,p-IRS2'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-74736 GRB2-1:SOS1 binds p-IRS1,p-IRS2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74746 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-74746 ('GRB2-1:SOS1 binds p-Y427-SHC1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-74746 GRB2-1:SOS1 binds p-Y427-SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851804 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851804 ('Activated MET recruits GRB2-1:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851804 Activated MET recruits GRB2-1:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851827 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851827 ('RAS guanyl nucleotide exchange by MET-bound GRB2:SOS1'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851827 RAS guanyl nucleotide exchange by MET-bound GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851859 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851859 ('Activated MET binds RANBP9 and SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851859 Activated MET binds RANBP9 and SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851877 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851877 ('RAS guanyl nucleotide exchange by SOS1 associated with RANBP9 and MET'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851877 RAS guanyl nucleotide exchange by SOS1 associated with RANBP9 and MET file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851899 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851899 ('RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851899 RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851900 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8851900 ('SHC1-2 bound to MET recruits GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8851900 SHC1-2 bound to MET recruits GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853734 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8853734 ('2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8853734 2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8854899 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-8854899 ('2x p-5Y-RET:GDNF:GFRA complexes bind GRB2-1:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-8854899 2x p-5Y-RET:GDNF:GFRA complexes bind GRB2-1:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9032073 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9032073 ('NTRK2-phosphorylated FRS2 binds GRB2'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-9032073 NTRK2-phosphorylated FRS2 binds GRB2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9607301 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9607301 ('Active FLT3:GRB2 binds SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9607301 Active FLT3:GRB2 binds SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9607304 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9607304 ('SOS1-mediated nucleotide exchange of RAS downstream of FLT3'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9607304 SOS1-mediated nucleotide exchange of RAS downstream of FLT3 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634402 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9634402 ('Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 homodimer'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9634402 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 homodimer file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634418 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9634418 ('RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9634418 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664983 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9664983 ('Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9664983 Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664991 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9664991 ('RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9664991 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665000 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665000 ('Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665000 Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665009 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665009 ('RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665009 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665404 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665404 ('RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665404 RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665408 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665408 ('RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR through GRB2'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665408 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR through GRB2 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665409 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665409 ('GRB2:SOS1 binds to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665409 GRB2:SOS1 binds to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665413 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665413 ('Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR recruit GRB2:SOS1 through SHC1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665413 Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR recruit GRB2:SOS1 through SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665698 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665698 ('Phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR bind GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665698 Phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR bind GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665699 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665699 ('Phosphorylated heterodimers of ERBB2 TMD/JMD mutants recruit GRB2:SOS1 through SHC1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665699 Phosphorylated heterodimers of ERBB2 TMD/JMD mutants recruit GRB2:SOS1 through SHC1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665700 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665700 ('RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665700 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665707 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9665707 ('RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9665707 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670428 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9670428 ('KIT mutants bind GRB2-SOS'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9670428 KIT mutants bind GRB2-SOS file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670436 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9670436 ('p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9670436 p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9672158 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9672158 ('GRB2:SOS1 complex binds to PDGFRA extracellular domain dimers'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-9672158 GRB2:SOS1 complex binds to PDGFRA extracellular domain dimers file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9672163 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9672163 ('SOS-mediated nucleotide exchange on RAS downstream of PDGFRA extracellular domain dimers'), a Rho-family GTPase activation event in which SOS1 is listed among candidate GEFs or signalosome members. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. The Rho/Rac-GEF relationship is secondary for SOS1 but does not affect the location annotation. Supporting Evidence: Reactome:R-HSA-9672163 SOS-mediated nucleotide exchange on RAS downstream of PDGFRA extracellular domain dimers file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9672164 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9672164 ('GRB2:SOS1 complex binds to mutant PDGFR receptor'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9672164 GRB2:SOS1 complex binds to mutant PDGFR receptor file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9672170 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9672170 ('SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9672170 SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9695845 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9695845 ('FLT3 mutant dimers:GRB2 bind SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9695845 FLT3 mutant dimers:GRB2 bind SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9695853 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9695853 ('FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9695853 FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9703430 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9703430 ('FLT3 fusions:GRB2 bind SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9703430 FLT3 fusions:GRB2 bind SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9703441 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9703441 ('SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants'), a RAS guanine-nucleotide exchange event catalysed by GRB2-bound SOS1. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9703441 SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983703 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-983703 ('p-6Y-SYK phosphorylates BLNK (SLP65)'), an immunoreceptor or RTK signalosome event in which the SOS1-containing complex is a participant but SOS1 does not catalyse the step. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. SOS1 is present as a complex member here; the location is still valid for SOS1. Supporting Evidence: Reactome:R-HSA-983703 p-6Y-SYK phosphorylates BLNK (SLP65) file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9842669 | ACCEPT | Summary: TAS cytosol from Reactome event Reactome:R-HSA-9842669 ('Active LTK recruits GRB2:SOS1'), a GRB2:SOS1 recruitment event to an activated receptor or adaptor. Reason: SOS1 is a soluble protein whose inactive pool is cytosolic and which is recruited from the cytosol to receptor complexes at the inner face of the plasma membrane; Reactome places SOS1 in the cytosol for this event. Supporting Evidence: Reactome:R-HSA-9842669 Active LTK recruits GRB2:SOS1 file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA plasma membrane (is_active_in) from the PTHR23113 SOS clade. Reason: SOS1 exerts its Ras-GEF activity at the cytoplasmic face of the plasma membrane, where prenylated Ras resides, after GRB2-mediated recruitment and allosteric Ras/PIP2 engagement. Supporting Evidence: PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation PMID:18454158 SOS has two binding sites for Ras, one of which is an allosteric site that is distal to the active site. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1112666 | ACCEPT | Summary: TAS plasma membrane from Reactome event Reactome:R-HSA-1112666 ('BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate'), in which GRB2:SOS1 is part of the BCR-BLNK signalosome. Reason: SOS1 is recruited to receptor signalosomes at the inner face of the plasma membrane where it activates Ras; the location is correct (as a peripheral, recruited protein). Supporting Evidence: Reactome:R-HSA-1112666 BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9606151 | ACCEPT | Summary: TAS plasma membrane from Reactome event Reactome:R-HSA-9606151 ('Phosphorylated BLNK (SLP65, in Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1) binds BTK, PLCG2, VAV1, NCK1'), in which GRB2:SOS1 is part of the BCR-BLNK signalosome. Reason: SOS1 is recruited to receptor signalosomes at the inner face of the plasma membrane where it activates Ras; the location is correct (as a peripheral, recruited protein). Supporting Evidence: Reactome:R-HSA-9606151 Phosphorylated BLNK (SLP65, in Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1) binds BTK, PLCG2, VAV1, NCK1 PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9691421 | ACCEPT | Summary: TAS plasma membrane from Reactome event Reactome:R-HSA-9691421 ('BTK binds BTK inhibitors'), in which GRB2:SOS1 is part of the BCR-BLNK signalosome. Reason: SOS1 is recruited to receptor signalosomes at the inner face of the plasma membrane where it activates Ras; the location is correct (as a peripheral, recruited protein). Supporting Evidence: Reactome:R-HSA-9691421 BTK binds BTK inhibitors PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-983703 | ACCEPT | Summary: TAS plasma membrane from Reactome event Reactome:R-HSA-983703 ('p-6Y-SYK phosphorylates BLNK (SLP65)'), in which GRB2:SOS1 is part of the BCR-BLNK signalosome. Reason: SOS1 is recruited to receptor signalosomes at the inner face of the plasma membrane where it activates Ras; the location is correct (as a peripheral, recruited protein). Supporting Evidence: Reactome:R-HSA-983703 p-6Y-SYK phosphorylates BLNK (SLP65) PMID:16520382 The translocation of the grb2–sos1 complex from the cytosol to the membrane upon RTK activation allows the presentation of sos1 to ras, leading to the exchange of GDP for GTP and ras activation |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras. | MARK AS OVER ANNOTATED | Summary: IDA regulation of transcription by RNA polymerase II from a study of Ras-driven Wnt4 repression and cell motility. Reason: SOS1 has no direct role in transcription; any effect on RNA polymerase II transcription is a downstream consequence of Ras-ERK signalling. The cached abstract does not mention SOS1, so the specific experiment cannot be checked, but on biological grounds this process is too indirect to describe SOS1 function. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md these are downstream consequences of RAS activation—not reactions catalyzed by SOS1 |
| GO:0007165 signal transduction | NAS PMID:8493579 Human Sos1: a guanine nucleotide exchange factor for Ras tha... | MODIFY | Summary: NAS signal transduction from the hSos1 cloning paper. Reason: Correct but very general; the paper supports the specific process Ras protein signal transduction (coupling of RTKs to Ras). Proposed replacements: Ras protein signal transduction Supporting Evidence: PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:8663461 Insulin and epidermal growth factor receptors regulate disti... | KEEP AS NON CORE | Summary: IDA epidermal growth factor receptor signaling pathway from a study of distinct Grb2-SOS pools used by insulin and EGF receptors. Reason: Correct: GRB2-SOS1 couples activated EGFR (directly or via SHC1) to Ras. EGFR is one of many receptor contexts; the core process is Ras protein signal transduction. Supporting Evidence: PMID:8663461 these data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc |
| GO:0007173 epidermal growth factor receptor signaling pathway | TAS Reactome:R-HSA-177929 | KEEP AS NON CORE | Summary: TAS epidermal growth factor receptor signaling pathway from the Reactome 'Signaling by EGFR' pathway. Reason: Correct receptor context for SOS1-mediated Ras activation; non-core relative to Ras protein signal transduction. Supporting Evidence: Reactome:R-HSA-177929 Recruitment of complexes containing GRB2 and SOS1 to phosphorylated EGFR dimers |
| GO:0007264 small GTPase-mediated signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: IEA small GTPase-mediated signal transduction from RasGEF InterPro signatures. Reason: Correct but general parent of GO:0007265 Ras protein signal transduction, which is accepted as core. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0007265 Ras protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA Ras protein signal transduction from PAINT node PTN000560991 (SOS clade). Reason: Core process: SOS1 converts Ras-GDP to Ras-GTP downstream of receptor tyrosine kinases and immunoreceptors. Supporting Evidence: PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0007265 Ras protein signal transduction | IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras. | ACCEPT | Summary: IDA Ras protein signal transduction from a study of Ras-induced motility and Wnt4 repression. Reason: The cached abstract does not mention SOS1, so the specific assay cannot be verified, but the process is the core function of SOS1; deferring to the curator. Supporting Evidence: PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. |
| GO:0007265 Ras protein signal transduction | IDA PMID:38188543 Studying early structural changes in SOS1 mediated KRAS acti... | ACCEPT | Summary: IDA Ras protein signal transduction from a structural/dynamics study of SOS1-mediated KRAS activation. Reason: Core process; the paper studies SOS1 as the exchange factor activating KRAS. Supporting Evidence: PMID:38188543 SOS1 is a GEF that activates KRAS, so called as the pacemaker of KRAS |
| GO:0007265 Ras protein signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: IEA Ras protein signal transduction transferred from rat Sos1 (D4A3T0). Reason: Core process, consistent with IBA and experimental annotations. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0007265 Ras protein signal transduction | TAS PMID:8493579 Human Sos1: a guanine nucleotide exchange factor for Ras tha... | ACCEPT | Summary: TAS Ras protein signal transduction from the hSos1 cloning paper. Reason: Core process: the paper establishes the GRB2-hSos1 complex as the coupler of RTKs to Ras. Supporting Evidence: PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. |
| GO:0007411 axon guidance | TAS Reactome:R-HSA-422475 | KEEP AS NON CORE | Summary: TAS axon guidance from the Reactome 'Axon guidance' pathway, which contains NCAM1-FAK-GRB2-SOS Ras activation events. Reason: SOS1 is included because GRB2:SOS1 activates Ras downstream of NCAM1 and other guidance receptors; this is a pathway-membership inference and one of many contexts for SOS1 Ras-GEF activity. Supporting Evidence: Reactome:R-HSA-392054 NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras |
| GO:0008286 insulin receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA insulin receptor signaling pathway transferred from mouse Sos1 (Q62245), whose sources are IDA annotations. Reason: Plausible: GRB2-SOS1 binds phosphorylated IRS1/IRS2 and SHC1 after insulin stimulation. One of several receptor contexts, so non-core. Supporting Evidence: PMID:8663461 these data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc Reactome:R-HSA-74736 GRB2-1:SOS1 binds p-IRS1,p-IRS2 |
| GO:0014044 Schwann cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA Schwann cell development transferred from mouse Sos1 (Q62245), whose source is an IMP annotation. Reason: A developmental outcome downstream of Ras signalling in Schwann cells, based on a mouse genetic study not reviewed here. Retained as non-core; it does not describe SOS1's molecular role. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md these are downstream consequences of RAS activation—not reactions catalyzed by SOS1 |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA postsynaptic density (is_active_in) transferred from rat Sos1 (D4A3T0), sourced from SynGO-style IDA annotations. Reason: Plausible neuronal location where SOS1 couples synaptic receptors to Ras; not a defining location, so non-core. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md SOS1 is therefore a soluble peripheral signaling protein rather than an integral membrane protein. |
| GO:0017124 SH3 domain binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA SH3 domain binding transferred from rat Sos1 (D4A3T0), whose source is an IPI annotation. Reason: Core: the SOS1 C-terminal proline-rich region contains multiple PXXP motifs bound by the SH3 domains of GRB2 and other adaptors, coupling SOS1 to activated receptors. Supporting Evidence: PMID:8493579 This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. PMID:19323566 the Grb2-Sos1 interaction is mediated through the combinatorial binding of nSH3 and cSH3 domains of Grb2 to various sites containing PXpsiPXR motifs within Sos1 file:human/SOS1/SOS1-uniprot.txt Interacts (via C-terminus) with GRB2 (via SH3 domain) |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-9607240 | KEEP AS NON CORE | Summary: TAS cytokine-mediated signaling pathway from the Reactome 'FLT3 Signaling' pathway. Reason: GRB2:SOS1 activates RAS downstream of FLT3 (receptor for the cytokine FLT3 ligand); a receptor-specific context of the core Ras-GEF function. Supporting Evidence: Reactome:R-HSA-9607304 SOS1-mediated nucleotide exchange of RAS downstream of FLT3 |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA protein kinase binding transferred from mouse Sos1 (Q62245), whose source is an IPI with the tyrosine kinase LCK. Reason: Plausible: SRC-family kinases such as LCK and HCK carry SH3 domains that bind the SOS1 proline-rich region. The more informative description of the interaction is SH3 domain binding; retained as non-core. Supporting Evidence: PMID:14679214 The proline-rich Sos peptide retrieved only SH3 domain containing proteins as specific binding partners. |
| GO:0035022 positive regulation of Rac protein signal transduction | IC PMID:16475793 Binding of laminin alpha1-chain LG4-5 domain to alpha-dystro... | ACCEPT | Summary: IC positive regulation of Rac protein signal transduction from a study of laminin-dystroglycan-syntrophin signalling through Grb2-Sos1-Rac1. Reason: SOS1 has a secondary, context-dependent Rac-GEF activity through its DH-PH unit in the EPS8-ABI1(E3B1) tricomplex, which positively regulates Rac signalling; this paper places Sos1 upstream of Rac1 in muscle. Supporting Evidence: PMID:16475793 by way of Grb2-Sos1-Rac1-PAK1-JNK ultimately results in the phosphorylation of c-jun on Ser(65) PMID:11777939 Grb2 and E3b1 bind through their SH3 domains to the same binding site on Sos-1, thus determining the formation of either a Sos-1-Grb2 (S/G) or a Sos-1-E3b1-Eps8 (S/E/E8) complex, endowed with Ras- and Rac-specific GEF activities, respectively PMID:9438849 the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo |
| GO:0038095 Fc-epsilon receptor signaling pathway | TAS Reactome:R-HSA-2454202 | KEEP AS NON CORE | Summary: TAS Fc-epsilon receptor signaling pathway from the Reactome FCERI signalling pathway. Reason: GRB2:SOS1 is recruited to LAT/NTAL and SHC1 in mast-cell FCERI signalling to activate Ras; an immunoreceptor context of the core function. Supporting Evidence: Reactome:R-HSA-2454202 Tyrosoine phosphorylation of enzymes and adaptors, including VAV, SHC GRB2 and SOS stimulate small GTPases |
| GO:0042110 T cell activation | IDA PMID:7737275 T cell antigen CD28 binds to the GRB-2/SOS complex, regulato... | KEEP AS NON CORE | Summary: IDA T cell activation from a study showing CD28 recruits the GRB2/SOS complex in T cells. Reason: SOS1 couples CD28/TCR-proximal adaptors to Ras in T cells, but T cell activation is a broad cellular outcome; retained as non-core. Supporting Evidence: PMID:7737275 CD28 also associates with the gene product of the human homolog of the Drosophila Son of sevenless gene (SOS) |
| GO:0042127 regulation of cell population proliferation | IDA PMID:9054499 Oncogenic ras provokes premature cell senescence associated ... | MARK AS OVER ANNOTATED | Summary: IDA regulation of cell population proliferation from the study showing oncogenic Ras induces premature senescence. Reason: The cached abstract concerns oncogenic Ras and does not mention SOS1, and the full text is not available, so what was assayed for SOS1 cannot be verified and the annotation is not removed. On biological grounds, however, effects on cell population proliferation (here, Ras-induced senescence) are downstream outcomes of Ras-ERK signalling rather than an activity of SOS1, so the term over-annotates SOS1 relative to its core Ras-GEF function. Supporting Evidence: PMID:9054499 expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest |
| GO:0042127 regulation of cell population proliferation | NAS PMID:38188543 Studying early structural changes in SOS1 mediated KRAS acti... | MARK AS OVER ANNOTATED | Summary: NAS regulation of cell population proliferation from a structural/dynamics study of SOS1-KRAS activation. Reason: Proliferation is a downstream outcome of Ras-ERK signalling rather than an activity of SOS1; the paper is a structural study of exchange and a statement-level (NAS) basis for this broad process is an over-annotation. Supporting Evidence: PMID:38188543 SOS1 is a GEF that activates KRAS, so called as the pacemaker of KRAS file:human/SOS1/SOS1-deep-research-falcon.md these are downstream consequences of RAS activation—not reactions catalyzed by SOS1 |
| GO:0042552 myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA myelination transferred from mouse Sos1 (Q62245), whose sources are IMP annotations. Reason: A developmental outcome of Ras signalling in myelinating glia from mouse genetic studies; retained as non-core. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md these are downstream consequences of RAS activation—not reactions catalyzed by SOS1 |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA neuronal cell body transferred from rat Sos1 (D4A3T0), sourced from an IDA. Reason: Consistent with a cytosolic protein present in neurons; a cell-type-specific location, so non-core. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md In unstimulated cells, SOS1 is largely cytosolic and conformationally restrained. |
| GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA positive regulation of epidermal growth factor receptor signaling pathway transferred from rat Sos1 (D4A3T0), sourced from an IEP. Reason: SOS1 is a mediator within EGFR signalling (captured by GO:0007173 and GO:0007265), not a regulator of the pathway; the rat source is expression-pattern (IEP) evidence, which does not support a regulatory role. Supporting Evidence: PMID:8663461 these data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc |
| GO:0046982 protein heterodimerization activity | IEA GO_REF:0000002 | REMOVE | Summary: IEA protein heterodimerization activity from the InterPro histone-fold signature (IPR009072) via InterPro2GO. Reason: The InterPro2GO mapping fits true histone-fold heterodimers (H2A/H2B, NF-Y) but not SOS proteins, whose N-terminal tandem histone folds lie within one polypeptide and serve autoinhibition and membrane binding. There is no evidence that SOS1 heterodimerizes through this region (consistent with the SOS2 review). Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md Regulatory rather than catalytic; interact with the DH–PH linker and help stabilize the closed, autoinhibited conformation. PMID:20133692 the histone domain plays a dual role in occluding the allosteric site and in stabilizing the autoinhibitory conformation of the DH-PH unit |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA insulin-like growth factor receptor signaling pathway transferred from mouse Sos1 (Q62245), sourced from an IDA. Reason: Plausible receptor context (IGF1R-IRS/SHC1-GRB2-SOS1-Ras); non-core. Supporting Evidence: PMID:8493579 These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. |
| GO:0048011 neurotrophin TRK receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA neurotrophin TRK receptor signaling pathway transferred from rat Sos1 (D4A3T0), sourced from an IMP. Reason: Plausible receptor context: TRK receptors recruit GRB2:SOS1 via FRS2/SHC1 to activate Ras; non-core. Supporting Evidence: Reactome:R-HSA-9032073 NTRK2-phosphorylated FRS2 binds GRB2 |
| GO:0050853 B cell receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA B cell receptor signaling pathway transferred from mouse Sos1 (Q62245), sourced from an IGI with Sos2. Reason: Plausible: GRB2:SOS1 is recruited to the BLNK signalosome after BCR engagement; an immunoreceptor context, non-core. Supporting Evidence: Reactome:R-HSA-9606151 Phosphorylated BLNK (SLP65, in Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1) binds BTK, PLCG2, VAV1, NCK1 |
| GO:0050900 leukocyte migration | TAS Reactome:R-HSA-202733 | MARK AS OVER ANNOTATED | Summary: TAS leukocyte migration from the Reactome pathway 'Cell surface interactions at the vascular wall'. Reason: SOS1 appears in this pathway through GRB2:SOS1 recruitment to TIE2 (angiopoietin receptor) in endothelial cells, which is Ras activation downstream of an RTK rather than a role in leukocyte migration. The process term is a pathway-membership over-annotation. Supporting Evidence: Reactome:R-HSA-210977 Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos) |
| GO:0051057 positive regulation of small GTPase mediated signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA positive regulation of small GTPase mediated signal transduction transferred from rat Sos1 (D4A3T0), sourced from an IMP. Reason: Consistent with SOS1 activating Ras and Rac by nucleotide exchange; the more specific process terms (Ras protein signal transduction, positive regulation of Rac signal transduction) are preferred. Supporting Evidence: file:human/SOS1/SOS1-uniprot.txt Promotes the exchange of Ras-bound GDP by GTP |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA glutamatergic synapse (is_active_in) transferred from rat Sos1 (D4A3T0), sourced from SynGO-style IDA annotations. Reason: Plausible neuronal location; non-core. Supporting Evidence: file:human/SOS1/SOS1-deep-research-falcon.md SOS1 is therefore a soluble peripheral signaling protein rather than an integral membrane protein. |
| GO:0140693 molecular condensate scaffold activity | IDA PMID:27056844 Phase separation of signaling molecules promotes T cell rece... | KEEP AS NON CORE | Summary: IDA molecular condensate scaffold activity from reconstitution of pLAT-GRB2-SOS1 phase separation on supported bilayers. Reason: Directly shown: multivalent SOS1 (several GRB2-binding PXXP sites) is required with GRB2 for pLAT condensate formation, which promotes Ras activation in TCR signalling. A genuine but context-specific scaffolding role that derives from its SH3-ligand tail; non-core relative to Ras-GEF activity. Supporting Evidence: PMID:27056844 pLAT, Grb2, and Sos1 all colocalized within clusters, and clusters did not form if either Grb2 or Sos1 was omitted |
| GO:1905360 GTPase complex | IPI PMID:25695162 Small molecule binding sites on the Ras:SOS complex can be e... | MARK AS OVER ANNOTATED | Summary: IPI GTPase complex from a fragment-screening crystallography study of the Ras:SOS complex. Reason: The Ras:SOS1 complex is a transient enzyme-substrate intermediate containing nucleotide-free Ras; it is not a stable complex capable of GTPase activity (GO:1905360 definition). The interaction is fully captured by SOS1 guanyl-nucleotide exchange factor activity (with Ras as substrate). Supporting Evidence: PMID:25695162 three fragment binding sites on the Ras:SOS complex PMID:9690470 The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. |
| GO:1905360 GTPase complex | IPI PMID:39043660 Allosteric nanobodies to study the interactions between SOS1... | MARK AS OVER ANNOTATED | Summary: IPI GTPase complex from a nanobody study of SOS1-RAS complex formation. Reason: As above: the SOS1:RAS complex is the catalytic intermediate of nucleotide exchange, not a GTPase-active complex; the relationship is captured by SOS1 guanyl-nucleotide exchange factor activity. Supporting Evidence: PMID:39043660 modulate the nucleotide exchange rate on this pivotal GTPase in vitro as well as RAS signalling in cellulo |
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Download this section (compressed HTML)Q: How much of SOS1-dependent RAC1 activation in vivo reflects direct DH-domain catalysis within the EPS8-ABI1 complex versus scaffolding or indirect Ras-PI3K-dependent Rac activation?
Q: Should the Ras:SOS1 catalytic intermediate be represented in GO-CAM as SOS1 GEF activity with Ras as has_input (and allosteric Ras-GTP as a positive regulator), rather than as a GTPase complex?
Q: Do Noonan syndrome SOS1 variants in the histone, PH and linker regions act solely by relieving autoinhibition, or do some also change Rac-GEF output or membrane residence time?
Experiment: Reconstitute full-length SOS1 with EPS8 and ABI1 on supported lipid bilayers and measure RAC1 versus HRAS/KRAS exchange side by side, including DH-domain catalytic mutants, to quantify the Rac-GEF branch.
Experiment: Single-molecule imaging of wild-type and Noonan-variant SOS1 on membranes with controlled Ras-GTP and PIP2 densities to relate allosteric-site occupancy to membrane dwell time and processive Ras activation.
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