SHC1 (ShcA) is a non-catalytic phosphotyrosine adaptor expressed from one gene as three major isoforms, p46Shc and p52Shc (alternative translation initiation) and p66Shc (alternative promoter, with an extra N-terminal CH2 region). All share an N-terminal PTB (PID) domain that recognises phosphorylated NPXpY motifs, a central collagen-homology (CH1) region, and a C-terminal SH2 domain. On activation of receptor tyrosine kinases (EGFR/ERBB family, insulin and IGF1 receptors, Trk, MET, KIT, ALK, Eph receptors and others), cytokine receptors and integrins, cytosolic SHC1 is recruited to receptor phosphotyrosines at the plasma membrane via its PTB and/or SH2 domain and is itself phosphorylated on CH1 tyrosines (Tyr239/Tyr240 and Tyr317, p52 numbering). These phosphotyrosines dock the GRB2 SH2 domain, bringing GRB2-SOS to the membrane to activate RAS and the RAF-MEK-ERK cascade, so p46/p52Shc act as receptor-to-RAS adaptors that support mitogenic and survival signalling; later-phase SHC1 complexes (for example with PEAK1/SgK269 and PTPN12) help reroute and terminate signalling. p46Shc carries an N-terminal mitochondrial targeting sequence and localises to the mitochondrial matrix. p66Shc does not promote RAS activation; after stress-induced Ser36 phosphorylation it moves to mitochondria and mitochondria-associated membranes, where it promotes hydrogen peroxide production and apoptosis in response to oxidative stress; in mice, loss of p66shc confers stress resistance and extends life span.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001784 phosphotyrosine residue binding | IPI PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | ACCEPT | Summary: SHC1 SH2 domain binds tyrosine-phosphorylated peptides of the Chlamydia trachomatis effector Tarp (serovar D, O84462). Reason: Direct, quantitative SH2-phosphopeptide binding; phosphotyrosine residue binding is a core SHC1 activity (PTB and SH2 domains). Supporting Evidence: PMID:20624904 We discovered numerous novel interactions between human SH2 domains and phosphopeptides derived from Tarp. The adaptor protein SHC1 was among Tarp's strongest interaction partners. |
| GO:0001784 phosphotyrosine residue binding | IPI PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | ACCEPT | Summary: SHC1 SH2 domain binds tyrosine-phosphorylated peptides of the Chlamydia trachomatis effector Tarp (serovar L2, Q6GX35). Reason: Direct, quantitative SH2-phosphopeptide binding; phosphotyrosine residue binding is a core SHC1 activity (PTB and SH2 domains). Supporting Evidence: PMID:20624904 We discovered numerous novel interactions between human SH2 domains and phosphopeptides derived from Tarp. The adaptor protein SHC1 was among Tarp's strongest interaction partners. |
| GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of RTK adaptor activity from mouse Shc1. Reason: SHC1 is the prototypical RTK adaptor: it binds activated receptor phosphotyrosines and, once phosphorylated, recruits GRB2-SOS. Consistent with experimental human evidence and the mouse GO-CAM insulin receptor model. Supporting Evidence: UniProt:P29353 Signaling adapter that couples activated growth factor receptors to signaling pathways. PMID:9544989 In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway. |
| GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity | TAS PMID:14676841 Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc... | ACCEPT | Summary: SHC1 links CD81 clustering to ERK/MAPK activation through PTB-dependent membrane recruitment. Reason: The adaptor function is correct for SHC1; although CD81 is a tetraspanin rather than an RTK, the core RTK adaptor activity is well established (PMID:1623525, PMID:9544989) and the TAS statement is acceptable. Supporting Evidence: PMID:14676841 we conclude that CD81 stimulates synthesis of phosphoinositides with the recruitment of Shc to the plasma membrane via PTB domain, and this sequence of events induces activation of ERK/MAPKinase PMID:1623525 These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells. |
| GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity | TAS PMID:1623525 A novel transforming protein (SHC) with an SH2 domain is imp... | ACCEPT | Summary: Original SHC description: SHC proteins complex with and are phosphorylated by the activated EGFR and couple growth factor receptors to mitogenic signalling. Reason: Core molecular function of SHC1 (p46/p52), mechanistically defined by later work (PTB/SH2 receptor binding, GRB2 recruitment). Supporting Evidence: PMID:1623525 These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. PMID:1623525 These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells. |
| GO:0005154 epidermal growth factor receptor binding | ISS GO_REF:0000024 | ACCEPT | Summary: EGFR binding transferred from rat Shc1. Reason: Well supported directly in human: SHC1 PTB and SH2 domains bind EGFR pY1148 and pY1173. Supporting Evidence: PMID:8034616 These results indicate that tyrosine 1148 of activated human EGF receptors is a major binding site of Shc and tyrosine 1173 is a secondary binding site in intact cells. |
| GO:0005158 insulin receptor binding | IPI PMID:7537849 Phosphotyrosine-dependent interaction of SHC and insulin rec... | ACCEPT | Summary: Two-hybrid and mutational analysis: SHC1 residues 1-238 (PTB) bind the autophosphorylated insulin receptor NPEY960 motif. Reason: Direct, phosphorylation-dependent binding to INSR; informative receptor-binding term consistent with SHC1 function in insulin signalling. Supporting Evidence: PMID:7537849 We conclude that SHC interacts directly with the IR and that phosphorylation of Tyr-960 within the IR juxtamembrane domain is necessary for efficient interaction. |
| GO:0005159 insulin-like growth factor receptor binding | IPI PMID:7541045 Non-SH2 domains within insulin receptor substrate-1 and SHC ... | ACCEPT | Summary: SHC1 amino-terminal (PTB) region binds the tyrosine-phosphorylated NPEY950 motif of IGF1R. Reason: Direct, phosphorylation-dependent binding to IGF1R demonstrated in vitro and by two-hybrid. Supporting Evidence: PMID:7541045 We conclude that SHC and IRS-1 interact with the tyrosine-phosphorylated NPEY motif of the IGFIR, and that both proteins interact via related motifs located in their amino termini. |
| GO:0005168 neurotrophin TRKA receptor binding | IPI PMID:15488758 TrkA alternative splicing: a regulated tumor-promoting switc... | ACCEPT | Summary: Interaction of SHC1 with TrkA (NTRK1) reported in a study of the TrkAIII splice variant in neuroblastoma. Reason: The cached abstract does not describe the SHC1 assay, but SHC1 binding to phosphorylated Trk receptors via its PTB/SH2 domains is well established and UniProt cites this paper for the interaction; deferring to the curator. Supporting Evidence: PMID:15488758 TrkAIII antagonizes NGF/TrkAI signaling, which is responsible for NB growth arrest and differentiation through Ras/MAPK UniProt:P29353 Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. |
| GO:0005515 protein binding | IPI PMID:10356320 Solution structure of the SH2 domain of Grb2 complexed with ... | REMOVE | Summary: NMR structure of the GRB2 SH2 domain complexed with a SHC1-derived phosphotyrosine peptide (WITH/FROM GRB2). Reason: This is a structural/biophysical study of the GRB2 SH2 domain bound to a synthetic SHC1-derived phosphopeptide (pY317 region). The binding activity belongs to GRB2; SHC1 only contributes the docking motif, and the peptide experiment does not demonstrate an activity of full-length SHC1 (no receptor bridging is shown). Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:10356320 The solution structure of growth factor receptor-bound protein 2 (Grb2) SH2 complexed with a Shc-derived phosphotyrosine (pTyr)-containing peptide was determined by nuclear magnetic resonance (NMR) spectroscopy. |
| GO:0005515 protein binding | IPI PMID:11694516 Shc and CEACAM1 interact to regulate the mitogenic action of... | MODIFY | Summary: Phosphorylated Tyr488 in the CEACAM1 cytoplasmic tail binds the SHC1 SH2 domain, sequestering SHC1 from the insulin receptor. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:11694516 Co-immunoprecipitation experiments in intact NIH 3T3 cells and glutathione S-transferase pull-down assays revealed that phosphorylated Tyr(488) in CEACAM1 binds to the SH2 domain of Shc, another substrate of the insulin receptor. |
| GO:0005515 protein binding | IPI PMID:11827484 Crystal structures of the SH2 domain of Grb2: highlight on t... | REMOVE | Summary: Crystal structures of the GRB2 SH2 domain bound to SHC1-derived phosphopeptides and a peptidomimetic inhibitor (WITH/FROM GRB2). Reason: This is a structural/biophysical study of the GRB2 SH2 domain bound to a synthetic SHC1-derived phosphopeptide (pY317 region). The binding activity belongs to GRB2; SHC1 only contributes the docking motif, and the peptide experiment does not demonstrate an activity of full-length SHC1 (no receptor bridging is shown). Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:11827484 we have solved the crystal structure of complexes between the Grb2-SH2 domain and peptides corresponding to Shc-derived sequences |
| GO:0005515 protein binding | IPI PMID:11877420 Tyrosine phosphorylation of the beta-amyloid precursor prote... | MODIFY | Summary: The APP cytoplasmic YENPTY motif, when phosphorylated on Tyr682, binds the SHC1 PTB domain; endogenous APP and ShcA associate after tyrosine phosphorylation. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:11877420 The APP cytoplasmic tail contains a PTB-binding motif (Y(682)ENPTY(687)) that, when phosphorylated on Tyr(682), precipitated the PTB domain of Shc A and Shc C, as well as endogenous full-length Shc A. |
| GO:0005515 protein binding | IPI PMID:12213123 Novel peptide inhibitors for Grb2 SH2 domain and their detec... | REMOVE | Summary: Design of non-phosphorylated peptide inhibitors of the GRB2 SH2 domain measured by SPR (WITH/FROM GRB2). Reason: The study is about peptide inhibitors of the GRB2 SH2 domain; SHC1 does not appear in the cached abstract and at most served as a reference ligand. No SHC1 activity is demonstrated. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:12213123 herein we report the design and synthesis of new peptide analogs, and their inhibitory effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology |
| GO:0005515 protein binding | IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:12577067 EGFR and Shc, which interact directly with the bait, had large differential ratios. |
| GO:0005515 protein binding | IPI PMID:15629149 Comparative analysis of the signaling capabilities of the in... | MODIFY | Summary: Yeast two-hybrid comparison of INSR, IGF1R and IRR: SHC1 binds the autophosphorylated insulin receptor intracellular domain; interaction tracks receptor autophosphorylation. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Here, interaction depends on receptor autophosphorylation (consistent with PTB recognition of the INSR NPEpY960 motif, PMID:7537849). Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:15629149 The reestablishment of autophosphorylation was paralleled by restoration of interaction with a specific range of signaling molecules. PMID:7537849 We conclude that SHC interacts directly with the IR and that phosphorylation of Tyr-960 within the IR juxtamembrane domain is necessary for efficient interaction. |
| GO:0005515 protein binding | IPI PMID:15657067 Phosphotyrosine signaling networks in epidermal growth facto... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with EGFR (WITH/FROM P00533). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated EGFR is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:15657067 Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CALCOCO2 (WITH/FROM Q13137). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: Quantitative SH2/PTB-domain protein-microarray binding of SHC1 domains to EGFR phosphotyrosine peptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:16273093 Here we use protein microarrays comprising virtually every Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors. |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: Quantitative SH2/PTB-domain protein-microarray binding of SHC1 domains to ERBB2 phosphotyrosine peptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:16273093 Here we use protein microarrays comprising virtually every Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors. |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: Quantitative SH2/PTB-domain protein-microarray binding of SHC1 domains to ERBB3 phosphotyrosine peptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:16273093 Here we use protein microarrays comprising virtually every Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors. |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MODIFY | Summary: Quantitative SH2/PTB-domain protein-microarray binding of SHC1 domains to ERBB4 phosphotyrosine peptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:16273093 Here we use protein microarrays comprising virtually every Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors. |
| GO:0005515 protein binding | IPI PMID:16843263 HER2 kinase domain mutation results in constitutive phosphor... | REMOVE | Summary: HER2(YVMA) mutant associates with and activates signal transducers more potently than wild-type HER2. Reason: The cached abstract does not name SHC1 or define the binding mode; SHC1 is presumably one of the 'signal transducers' co-precipitated with HER2. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:16843263 Expression of a HER2 mutant containing a G776(YVMA) insertion in exon 20 was more potent than wild-type HER2 in associating with and activating signal transducers, phosphorylating EGFR, and inducing survival, invasiveness, and tumorigenicity. |
| GO:0005515 protein binding | IPI PMID:19172738 Phosphorylation-dependent binding of 14-3-3 terminates signa... | REMOVE | Summary: SHC1 is recruited into GAB2 signalosomes in a GRB2-dependent manner. Reason: The SHC1-GAB2 association is indirect (GRB2-mediated) and no SHC1 activity is defined. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:19172738 First, the signalosomes assembled by the 14-3-3-binding-deficient Gab2 mutants 2 Γ A and 2 Γ E contain increased amounts of not only Grb2 but also Shc and the EGFR, which are both recruited in a Grb2-dependent manner |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:19380743 Charting the molecular network of the drug target Bcr-Abl |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:19380743 Charting the molecular network of the drug target Bcr-Abl |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | REMOVE | Summary: High-throughput interaction evidence for SHC1 with SOS1 (WITH/FROM Q07889). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:19380743 Charting the molecular network of the drug target Bcr-Abl |
| GO:0005515 protein binding | IPI PMID:20010870 Copine-III interacts with ErbB2 and promotes tumor cell migr... | REMOVE | Summary: Copine-III (CPNE3) binds phosphorylated ErbB2 Tyr1248 and was found associated with SHC1. Reason: The SHC1-CPNE3 association may help link CPNE3 to ERBB2, but the paper does not establish an SHC1 activity beyond co-association. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:20010870 Copine-III, a member of a Ca(2+)-dependent phospholipid-binding protein family, was identified as binding to phosphorylated Tyr1248 of ErbB2. |
| GO:0005515 protein binding | IPI PMID:20935677 A positive feedback loop of ER-Ξ±36/EGFR promotes malignant g... | REMOVE | Summary: EGFR/Src/Shc complex co-immunoprecipitated with ER-alpha36 in ER-negative breast cancer cells. Reason: Co-immunoprecipitation of a multiprotein complex; the SHC1 activity involved is not defined. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:20935677 Figure 6A shows that EGFR, Src and Shc co-existed in the immunoprecipitates of the anti-HA antibody |
| GO:0005515 protein binding | IPI PMID:20935677 A positive feedback loop of ER-Ξ±36/EGFR promotes malignant g... | REMOVE | Summary: ER-alpha36 (ESR1 isoform 4) co-immunoprecipitates with an EGFR/Src/Shc complex. Reason: Complex co-immunoprecipitation; no direct SHC1 activity toward ER-alpha36 is defined. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:20935677 Figure 6A shows that EGFR, Src and Shc co-existed in the immunoprecipitates of the anti-HA antibody |
| GO:0005515 protein binding | IPI PMID:21278788 Translationally controlled tumor protein induces human breas... | REMOVE | Summary: TCTP-induced Src-dependent EGFR transactivation in breast epithelial cells. Reason: The cached abstract does not describe an SHC1 activity; the row appears to derive from EGFR complex co-IP in a TCTP signalling study. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:21278788 These findings suggest that TCTP induces tumorigenesis through distinct multicellular signaling pathways involving Src-dependent EGFR transactivation, ROS generation and MMP expression. |
| GO:0005515 protein binding | IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:21706016 Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor |
| GO:0005515 protein binding | IPI PMID:21725358 The SRC-associated protein CUB Domain-Containing Protein-1 r... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:21725358 The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and motility |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CBLC (WITH/FROM Q9ULV8). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:21900206 A directed protein interaction network for investigating intracellular signal transduction |
| GO:0005515 protein binding | IPI PMID:22057045 Phosphotyrosine mediated protein interactions of the discoid... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:22057045 Phosphotyrosine mediated protein interactions of the discoidin domain receptor 1 |
| GO:0005515 protein binding | IPI PMID:23178716 SnoN/SkiL expression is modulated via arsenic trioxide-induc... | MODIFY | Summary: Arsenic trioxide-activated EGFR engages p66 ShcA and GRB2; p66 ShcA knockdown reduces the EGFR-GRB2 association. Reason: SHC1 (p66) mediates the association of activated EGFR with GRB2, which is the RTK adaptor activity. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:23178716 We also noted reduced Grb2-EGFR interaction with p66 ShcA knockdown in the presence of As 2 O 3 implicating p66 ShcA isoform in mediating this interaction |
| GO:0005515 protein binding | IPI PMID:23178716 SnoN/SkiL expression is modulated via arsenic trioxide-induc... | MODIFY | Summary: Arsenic trioxide activates EGFR and promotes p66 ShcA phosphorylation and GRB2 association; p66 ShcA knockdown reduces GRB2-EGFR association. Reason: The study shows that receptor-activated, tyrosine-phosphorylated SHC1 recruits GRB2 (and thereby SOS), i.e. SHC1 bridges the activated receptor tyrosine kinase to GRB2. This is the adaptor function; replace bare protein binding with transmembrane receptor protein tyrosine kinase adaptor activity. Here the knockdown shows SHC1 (p66 isoform) mediates the EGFR-GRB2 association. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:23178716 We also noted reduced Grb2-EGFR interaction with p66 ShcA knockdown in the presence of As 2 O 3 implicating p66 ShcA isoform in mediating this interaction |
| GO:0005515 protein binding | IPI PMID:23799367 Threshold-controlled ubiquitination of the EGFR directs rece... | REMOVE | Summary: EGFR-Shc co-immunoprecipitation used as a control interaction in a study of EGFR ubiquitination thresholds. Reason: SHC1 is a control interactor in this study; no SHC1 activity is characterised. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:23799367 an effect that was not evident when the physical association of EGFR with other known interactors, such as Grb2 or Shc, was analysed |
| GO:0005515 protein binding | IPI PMID:23846654 Temporal regulation of EGF signalling networks by the scaffo... | MODIFY | Summary: SgK269/PEAK1 binds the SHC1 PTB domain through a phosphorylated NPXY site (Y1188) in the late phase of EGF signalling. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:23846654 SgK269 binds the Shc1 PTB domain through a phosphorylated NPXY site, and brings in Ppp1c serine/threonine phosphatases and other Cluster 3 proteins |
| GO:0005515 protein binding | IPI PMID:24008843 Structure homology and interaction redundancy for discoverin... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with influenza A virus NS1 (WITH/FROM P03495). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24008843 Structure homology and interaction redundancy for discovering virus-host protein interactions |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with EGFR (WITH/FROM P00533). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated EGFR is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24189400 Mutant EGFR pulldowns identified MAPK adaptors GRB2 and SHC1 as well as ERRFI and UBS3B tyrosine phosphatase |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ERBB3 (WITH/FROM P21860). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ERBB3 is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24189400 ERBB3 also co-purified EGFR and the adaptor proteins GRB2 and SHC1 |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24189400 Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24189400 Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24412244 Charting the molecular links between driver and susceptibility genes in colorectal cancer |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with SMAD4 (WITH/FROM Q13485). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:24412244 Charting the molecular links between driver and susceptibility genes in colorectal cancer |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: Fluorescence-polarisation interactome of SH2/PTB domains with phosphopeptides from c-Met, c-Kit, GAB1 and androgen receptor; SHC1 domains bound MET-derived phosphopeptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24728074 We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. PMID:24728074 SHC1 SH2 domain interactions were identified with peptides derived from Tyr(P)-83, Tyr(P)-95, Tyr(P)-183, Tyr(P)-373, Tyr(P)-627, and Tyr(P)-689 |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: Fluorescence-polarisation interactome of SH2/PTB domains with phosphopeptides from c-Met, c-Kit, GAB1 and androgen receptor; SHC1 domains bound AR-derived phosphopeptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24728074 We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. PMID:24728074 SHC1 SH2 domain interactions were identified with peptides derived from Tyr(P)-83, Tyr(P)-95, Tyr(P)-183, Tyr(P)-373, Tyr(P)-627, and Tyr(P)-689 |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: Fluorescence-polarisation interactome of SH2/PTB domains with phosphopeptides from c-Met, c-Kit, GAB1 and androgen receptor; SHC1 domains bound KIT-derived phosphopeptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24728074 We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. PMID:24728074 SHC1 SH2 domain interactions were identified with peptides derived from Tyr(P)-83, Tyr(P)-95, Tyr(P)-183, Tyr(P)-373, Tyr(P)-627, and Tyr(P)-689 |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MODIFY | Summary: Fluorescence-polarisation interactome of SH2/PTB domains with phosphopeptides from c-Met, c-Kit, GAB1 and androgen receptor; SHC1 domains bound GAB1-derived phosphopeptides. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:24728074 We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. PMID:24728074 SHC1 SH2 domain interactions were identified with peptides derived from Tyr(P)-83, Tyr(P)-95, Tyr(P)-183, Tyr(P)-373, Tyr(P)-627, and Tyr(P)-689 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:26551075 EGF-receptor specificity for phosphotyrosine-primed substrat... | REMOVE | Summary: SHC1-derived peptides are phosphorylated by EGFR after Src priming; crystal structure of EGFR with a primed Shc1 peptide. Reason: Here SHC1 is the substrate of the EGFR kinase; the interaction reflects EGFR substrate recognition, which is an EGFR activity, not an SHC1 molecular function. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:26551075 Utilizing peptides based on the sequence of the adaptor protein Shc1, we show that Src mediates the priming phosphorylation, promoting subsequent phosphorylation by EGFR |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators |
| GO:0005515 protein binding | IPI PMID:28065597 A Global Analysis of the Receptor Tyrosine Kinase-Protein Ph... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with EGFR (WITH/FROM P00533). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated EGFR is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:28065597 A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome |
| GO:0005515 protein binding | IPI PMID:28065597 A Global Analysis of the Receptor Tyrosine Kinase-Protein Ph... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ERBB2 (WITH/FROM P04626). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ERBB2 is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:28065597 A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CALCOCO2 (WITH/FROM Q13137). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31515488 PSPH interactions with CIRBP and SHC1 were detected using PCA |
| GO:0005515 protein binding | IPI PMID:31585087 Oncogenic Mutations Rewire Signaling Pathways by Switching P... | MODIFY | Summary: Phosphotyrosine-peptide pulldown interaction proteomics assigned SHC1 recruitment to EGF-regulated EGFR phosphotyrosine sites. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. The approach is phosphopeptide-based, so the recruitment is phosphotyrosine-directed. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:31585087 we performed >1,000 phosphopeptide pulldowns and analyzed them by rapid mass spectrometric analysis |
| GO:0005515 protein binding | IPI PMID:31820037 Elucidation of protein interactions necessary for the mainte... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31820037 Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex |
| GO:0005515 protein binding | IPI PMID:31820037 Elucidation of protein interactions necessary for the mainte... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CBLC (WITH/FROM Q9ULV8). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31820037 Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with EGFR (WITH/FROM P00533). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated EGFR is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D) |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D) |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D) |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with PTPN12 (WITH/FROM Q05209). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. PTPN12 (PTP-PEST) is a phosphatase that engages and dephosphorylates SHC1; SHC1 is the substrate/partner, not the actor. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ALK (WITH/FROM Q9UM73). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ALK is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:34606829 Mapping the Phospho-dependent ALK Interactome to Identify No... | MODIFY | Summary: Mammalian membrane two-hybrid screen of SH2-domain proteins identified phospho-dependent ALK interactors including SHC1. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. The screen is explicitly phospho-dependent (sensitive to ALK kinase activity and inhibitors). Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:34606829 Many of their interactions are correlated to ALK phosphorylation activity: oncogenic ALK mutations potentiate the interactions and ALK inhibitors attenuate the interactions. |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CFTR (WITH/FROM P13569). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with EGFR (WITH/FROM P00533). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated EGFR is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ERBB2 (WITH/FROM P04626). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ERBB2 is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ERBB3 (WITH/FROM P21860). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ERBB3 is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with ALK (WITH/FROM Q9UM73). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. SHC1 binding to activated ALK is real and phosphotyrosine-directed, but that is captured on rows whose papers demonstrate phosphotyrosine recognition. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with SMAD4 (WITH/FROM Q13485). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:35512704 Systematic discovery of mutation-directed neo-protein-protein interactions in cancer |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with CFTR (WITH/FROM P13569). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interaction evidence for SHC1 with GRB2 (WITH/FROM P62993). Reason: High-throughput interaction-mapping evidence (affinity purification/proteomics, two-hybrid, or proximity labelling) that places SHC1 and the partner in the same complex or network without defining the SHC1 activity involved. The SHC1-GRB2 relationship is captured on the adaptor-activity rows supported by receptor-bridging evidence. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics |
| GO:0005515 protein binding | IPI PMID:7518560 Hierarchy of binding sites for Grb2 and Shc on the epidermal... | MODIFY | Summary: Phosphopeptide competition and dephosphorylation protection map EGFR pY1173 (major) and pY992 (minor) as SHC1 binding sites. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7518560 Both competition experiments with synthetic phosphopeptides and dephosphorylation protection analysis demonstrated that Y-1173 and Y-992 are major and minor binding sites, respectively, for Shc on the EGFR. |
| GO:0005515 protein binding | IPI PMID:7535773 Growth hormone-promoted tyrosyl phosphorylation of SHC prote... | MODIFY | Summary: The SHC1 SH2 domain binds tyrosine-phosphorylated JAK2 (mouse) downstream of growth hormone receptor. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7535773 Constitutively phosphorylated JAK2, from COS-7 cells transiently transfected with murine JAK2 cDNA, bound to SHC SH2-GST fusion protein, demonstrating that the SHC SH2 domain can bind tyrosyl-phosphorylated JAK2 in the absence of GHR. |
| GO:0005515 protein binding | IPI PMID:7542744 The phosphotyrosine interaction domain of Shc binds an LXNPX... | MODIFY | Summary: The SHC1 PTB (PI) domain binds the LXNPXpY motif around EGFR pY1148. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7542744 We demonstrate that the PI domain of Shc binds the LXNPXpY motif that encompasses Y-1148 of the activated EGFR. |
| GO:0005515 protein binding | IPI PMID:7559478 Distinct modes of interaction of SHC and insulin receptor su... | MODIFY | Summary: Mutational analysis of the insulin receptor NPEY motif: Tyr-960 is essential for SHC1 interaction (WITH/FROM insulin receptor Q9PVZ4). Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7559478 We confirm that Tyr-960 within the NPEY motif of the IR is essential for both IRS-1 and SHC interaction |
| GO:0005515 protein binding | IPI PMID:8034616 Tyrosines 1148 and 1173 of activated human epidermal growth ... | MODIFY | Summary: EGFR autophosphorylation-site mutants identify pY1148 as the major and pY1173 as a secondary SHC1 binding site in cells. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:8034616 These results indicate that tyrosine 1148 of activated human EGF receptors is a major binding site of Shc and tyrosine 1173 is a secondary binding site in intact cells. |
| GO:0005515 protein binding | IPI PMID:8491186 The SH2/SH3 domain-containing protein GRB2 interacts with ty... | MODIFY | Summary: In insulin-stimulated cells GRB2 forms a stable complex with tyrosine-phosphorylated SHC1; the interaction requires insulin receptor activation and GRB2 SH2 binding to SHC1 phosphotyrosines. Reason: The study shows that receptor-activated, tyrosine-phosphorylated SHC1 recruits GRB2 (and thereby SOS), i.e. SHC1 bridges the activated receptor tyrosine kinase to GRB2. This is the adaptor function; replace bare protein binding with transmembrane receptor protein tyrosine kinase adaptor activity. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:8491186 The interactions between GRB2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH2 domain of GRB2 to phosphotyrosines on both IRS-1 and Shc. |
| GO:0005515 protein binding | IPI PMID:8663178 Rapid identification of phosphopeptide ligands for SH2 domai... | REMOVE | Summary: Bead-library screen of SH2-domain phosphopeptide specificity (GRB2 selects pYENDP-type motifs) (WITH/FROM GRB2). Reason: A GRB2 SH2 specificity screen; the SHC1 contribution is a ligand motif at most. No SHC1 activity is demonstrated. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:8663178 the SH2 domain of the adapter protein Grb2 predominantly selected beads with the sequence Y*ENDP |
| GO:0005515 protein binding | IPI PMID:8939605 The Shc adaptor protein is highly phosphorylated at conserve... | MODIFY | Summary: Identification of SHC1 Tyr239/Tyr240 as major phosphorylation sites (EGF- or Src-induced) that contribute to GRB2 association. Reason: The study shows that receptor-activated, tyrosine-phosphorylated SHC1 recruits GRB2 (and thereby SOS), i.e. SHC1 bridges the activated receptor tyrosine kinase to GRB2. This is the adaptor function; replace bare protein binding with transmembrane receptor protein tyrosine kinase adaptor activity. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:8939605 Mutagenesis studies indicate that Y239/240 make an important contribution to the association of Shc with Grb2. PMID:8939605 Phosphorylation of Y317 has been implicated in Grb2 binding and activation of the Ras pathway. |
| GO:0005515 protein binding | IPI PMID:8940013 The Grb2-mSos1 complex binds phosphopeptides with higher aff... | REMOVE | Summary: Affinity measurements of GRB2 and GRB2-mSos1 for EGFR- and SHC1-derived phosphopeptides (WITH/FROM GRB2). Reason: This is a structural/biophysical study of the GRB2 SH2 domain bound to a synthetic SHC1-derived phosphopeptide (pY317 region). The binding activity belongs to GRB2; SHC1 only contributes the docking motif, and the peptide experiment does not demonstrate an activity of full-length SHC1 (no receptor bridging is shown). Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:8940013 An EGFR-derived phosphopeptide bound Grb2 with a KD of 0.7 microM, whereas the Shc-derived phosphopeptide bound Grb2 with a KD of 0.2 microM. |
| GO:0005515 protein binding | IPI PMID:8995379 The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 pro... | REMOVE | Summary: Characterisation of the GRB2-like lymphoid adaptor Grap, whose SH2 domain associates with Shc after TCR activation (WITH/FROM GRB2). Reason: The paper centres on Grap, a GRB2 paralog; the Shc association reported is SH2-mediated binding by Grap/GRB2 to phosphorylated Shc, i.e. an activity of the SH2 protein. Deferring to the curator on the GRB2 interaction itself. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:8995379 In Jurkat cells, T cell receptor activation leads to the association of Grap with phosphoproteins p36/38 and, to a lesser degree, Shc. |
| GO:0005515 protein binding | IPI PMID:9175774 An alternative to phosphotyrosine-containing motifs for bind... | REMOVE | Summary: Cell-permeable SHC1 Tyr317-region peptides bind the GRB2 SH2 domain even when unphosphorylated (WITH/FROM GRB2). Reason: This is a structural/biophysical study of the GRB2 SH2 domain bound to a synthetic SHC1-derived phosphopeptide (pY317 region). The binding activity belongs to GRB2; SHC1 only contributes the docking motif, and the peptide experiment does not demonstrate an activity of full-length SHC1 (no receptor bridging is shown). Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:9175774 cell-permeable peptides encompassing the Shc Tyr317 region, 312FDD-PSYVNVQNL323, can bind to the SH2 domain of Grb2 regardless of the state of tyrosine phosphorylation |
| GO:0005515 protein binding | IPI PMID:9254595 Thermodynamic and structural analysis of phosphotyrosine pol... | REMOVE | Summary: Isothermal titration calorimetry of the GRB2 SH2 domain binding a SHC1-derived pYVNV hexapeptide (WITH/FROM GRB2). Reason: This is a structural/biophysical study of the GRB2 SH2 domain bound to a synthetic SHC1-derived phosphopeptide (pY317 region). The binding activity belongs to GRB2; SHC1 only contributes the docking motif, and the peptide experiment does not demonstrate an activity of full-length SHC1 (no receptor bridging is shown). Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:9254595 Interaction of the Shc-derived phosphotyrosine hexapeptide Ac-SpYVNVQ-NH2 with Grb2-SH2 was both enthalpically and entropically favorable |
| GO:0005515 protein binding | IPI PMID:9544989 Shc phosphotyrosine-binding domain dominantly interacts with... | MODIFY | Summary: SHC1 PTB (R175K) and SH2 (R397K) mutants show EGFR pY1148 binds mainly the PTB domain and pY1173 both domains. Reason: The paper demonstrates that SHC1 recognises specific phosphorylated tyrosine residues on the partner via its PTB and/or SH2 domain. Replace bare protein binding with phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:9544989 The present results indicate that tyrosine 1148 of the activated EGF receptor mainly interacts with the Shc PTB domain in intact cells. |
| GO:0005515 protein binding | IPI PMID:9544989 Shc phosphotyrosine-binding domain dominantly interacts with... | MODIFY | Summary: p52Shc bound to the activated EGFR through its PTB domain associates with GRB2-SOS and supports Ras activation. Reason: The study shows that receptor-activated, tyrosine-phosphorylated SHC1 recruits GRB2 (and thereby SOS), i.e. SHC1 bridges the activated receptor tyrosine kinase to GRB2. This is the adaptor function; replace bare protein binding with transmembrane receptor protein tyrosine kinase adaptor activity. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:9544989 In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway. |
| GO:0005515 protein binding | IPI PMID:9544989 Shc phosphotyrosine-binding domain dominantly interacts with... | MODIFY | Summary: SHC1 bound to the activated EGFR through its PTB domain associates with the GRB2-SOS complex (WITH/FROM SOS1). Reason: SOS1 co-precipitates with SHC1 through GRB2 once SHC1 is bound to the activated receptor; the SHC1 activity represented is bridging the receptor to GRB2-SOS, i.e. RTK adaptor activity. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:9544989 In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway. |
| GO:0005515 protein binding | IPI PMID:9593725 Association of the insulin receptor with phospholipase C-gam... | REMOVE | Summary: Study of insulin receptor association with PLC-gamma in 3T3-L1 adipocytes. Reason: The cached abstract concerns PLCgamma-IR association and does not describe SHC1; SHC1 binding to the insulin receptor is separately captured by the insulin receptor binding (GO:0005158) and phosphotyrosine-binding rows. Removal of the bare protein binding term does not mean the reported interaction is false; the generic term carries no functional information about SHC1, whose informative activities are captured by the phosphotyrosine residue binding and RTK adaptor activity annotations. Supporting Evidence: PMID:9593725 In this paper, we present evidence for the association of the insulin receptor (IR) with PLCgamma. |
| GO:0005543 phospholipid binding | TAS PMID:14676841 Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc... | KEEP AS NON CORE | Summary: The SHC1 PTB domain interacts with phosphoinositides, supporting its plasma membrane recruitment. Reason: PTB-domain phosphoinositide binding is a documented auxiliary property that aids membrane targeting; it is secondary to phosphotyrosine recognition. Supporting Evidence: PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm from UniProt subcellular location mapping. Reason: SHC1 is a cytoplasmic adaptor recruited to membranes on receptor activation. Supporting Evidence: UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrion from UniProt subcellular location mapping (isoform p66Shc; p46Shc matrix). Reason: Isoform-specific: p46Shc has an N-terminal mitochondrial targeting sequence and p66Shc accumulates in or at mitochondria under oxidative stress. Not the location of the canonical p52Shc adaptor function. Supporting Evidence: PMID:14573619 Here we demonstrate the specific and selective localization of p46Shc to the mitochondrial matrix. PMID:16051147 We report here that p66Shc is a redox enzyme that generates mitochondrial ROS (hydrogen peroxide) as signaling molecules for apoptosis. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial matrix from UniProt subcellular location (isoform p46Shc). Reason: Supported experimentally for the p46Shc isoform, which carries a bona fide N-terminal mitochondrial targeting sequence; isoform-specific and not core to receptor adaptor function. Supporting Evidence: PMID:14573619 Through deletion mapping experiments, we show that targeting of p46Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide mitochondrial targeting sequence. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localisation from Human Protein Atlas immunofluorescence. Reason: SHC1 is predominantly cytosolic in unstimulated cells and is recruited to activated receptors at the membrane. Supporting Evidence: UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. file:human/SHC1/SHC1-deep-research-falcon.md SHC1 is primarily **cytosolic and ER-associated** under basal conditions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109822 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-109822 MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225947 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Binding of SHC1 to p-6Y-EGFR mutants'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1225947 Binding of SHC1 to p-6Y-EGFR mutants UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225952 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SHC1 by ligand-responsive p-6Y-EGFR mutants'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1225952 Phosphorylation of SHC1 by ligand-responsive p-6Y-EGFR mutants UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225957 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. 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) UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225961 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated SHC1 in complex with ligand-responsive p-6Y-EGFR mutants recruits GRB2:SOS1 complex'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1225961 Phosphorylated SHC1 in complex with ligand-responsive p-6Y-EGFR mutants recruits GRB2:SOS1 complex UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250195 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 phosphorylation by ERBB2 heterodimers'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250348 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SHC1 by ERBB4 homodimers'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250357 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 binds P-ERBB4 isoform dimers'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250380 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1250383 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177925 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 binds to the phosphorylated EGF receptor:ligand complex'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-177925 SHC1 binds to the phosphorylated EGF receptor:ligand complex UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177933 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 phosphorylation by phosphorylated EGFR'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-177933 SHC1 phosphorylation by phosphorylated EGFR UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177936 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-177936 GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177945 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-177945 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1) UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1791134 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Expression of SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-1791134 Expression of SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-204861 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Interaction of Tie2 and Shc1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-204861 Interaction of Tie2 and Shc1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396561 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of GADS:SLP-76 to p-5Y-LAT'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2396561 Recruitment of GADS:SLP-76 to p-5Y-LAT UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396594 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SLP-76 by p-SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2396594 Phosphorylation of SLP-76 by p-SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396599 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of GRB2:SOS to p-5Y-LAT'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2396599 Recruitment of GRB2:SOS to p-5Y-LAT UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396606 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2396606 Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2404193 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'IGF1R phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2404193 IGF1R phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424476 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activation of RAC1 by VAV2/3'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424476 Activation of RAC1 by VAV2/3 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424477 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SOS mediated nucleotide exchange of RAS (SHC)'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424477 SOS mediated nucleotide exchange of RAS (SHC) UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424481 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of VAV and BTK to p-SLP-76'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424481 Recruitment of VAV and BTK to p-SLP-76 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424484 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of BTK by p-SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424484 Phosphorylation of BTK by p-SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424485 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Release of p-PLCG1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424485 Release of p-PLCG1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424486 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation and activation of VAV2/VAV3 by SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424486 Phosphorylation and activation of VAV2/VAV3 by SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424487 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of PLC-gamma by p-BTK/p-SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2424487 Phosphorylation of PLC-gamma by p-BTK/p-SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730833 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of TEC kinases by p-SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730837 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of GRB2:SOS to p-10Y-NTAL'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730837 Recruitment of GRB2:SOS to p-10Y-NTAL UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730840 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activation of RAC1 by VAV'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730840 Activation of RAC1 by VAV UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730841 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation and activation of VAV'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730841 Phosphorylation and activation of VAV UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730842 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'PI3K associates with phosphorylated GAB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730842 PI3K associates with phosphorylated GAB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730844 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Interaction of GRB2:SOS complex with p-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730844 Interaction of GRB2:SOS complex with p-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730847 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Hydrolysis of PIP2 by PLCG'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730847 Hydrolysis of PIP2 by PLCG UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730851 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SLP-76 by p-SYK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730851 Phosphorylation of SLP-76 by p-SYK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730856 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Autophosphorylation of PAK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730856 Autophosphorylation of PAK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730858 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Autophosphorylation of BTK/ITK'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730858 Autophosphorylation of BTK/ITK UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730870 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of PIP2 to PIP3 by PI3K'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730870 Phosphorylation of PIP2 to PIP3 by PI3K UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730886 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SHC by SYK kinase'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730886 Phosphorylation of SHC by SYK kinase UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730889 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of PAK to the membrane by binding active RAC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730892 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of VAV to p-SLP-76'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-2730892 Recruitment of VAV to p-SLP-76 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432096 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated integrin alphaIIb beta3 binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-432096 Activated integrin alphaIIb beta3 binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443905 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-443905 SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443910 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 dissociates from integrin alphaIIb beta3'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-443910 SHC1 dissociates from integrin alphaIIb beta3 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452091 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of IL2RB Y338 enables SHC recruitment'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-452091 Phosphorylation of IL2RB Y338 enables SHC recruitment UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452100 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 bound to IL2 receptor is phosphorylated'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-452100 SHC1 bound to IL2 receptor is phosphorylated UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-453104 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated SHC1 recruits GRB2:GAB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-453104 Phosphorylated SHC1 recruits GRB2:GAB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-453111 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated SHC recruits GRB2:SOS1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-453111 Phosphorylated SHC recruits GRB2:SOS1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-508247 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Gab2 binds the p85 subunit of Class 1A PI3 kinases'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-508247 Gab2 binds the p85 subunit of Class 1A PI3 kinases UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637766 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Binding of SHC1 to p-5Y-EGFRvIII'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5637766 Binding of SHC1 to p-5Y-EGFRvIII UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637796 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SHC1 by p-5Y-EGFRvIII'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5637796 Phosphorylation of SHC1 by p-5Y-EGFRvIII UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637798 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated SHC1 in complex with p-5Y-EGFRvIII recruits GRB2:SOS1 complex'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5637798 Phosphorylated SHC1 in complex with p-5Y-EGFRvIII recruits GRB2:SOS1 complex UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637808 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII)'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5637808 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII) UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654404 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR2 binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654404 Activated FGFR2 binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654407 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR2 phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654407 Activated FGFR2 phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654425 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR4 binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654425 Activated FGFR4 binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654428 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR4 phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654428 Activated FGFR4 phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654573 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR1 binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654573 Activated FGFR1 binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654582 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR1 phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654582 Activated FGFR1 phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654625 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR3 binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654625 Activated FGFR3 binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654634 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated FGFR3 phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5654634 Activated FGFR3 phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS GEFs promote RAS nucleotide exchange'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5685366 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GRB2-1:SOS1 binds p-Y-SHC'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5685366 GRB2-1:SOS1 binds p-Y-SHC UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686072 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-3Y-SHC1 dissociates from IGF1R'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5686072 p-3Y-SHC1 dissociates from IGF1R UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686073 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GRB2-1:SOS1 binds p-3Y-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5686073 GRB2-1:SOS1 binds p-3Y-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5686074 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GRB2-1:p-4S-SOS1:p-Y427-SHC1 dissociates'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-5686074 GRB2-1:p-4S-SOS1:p-Y427-SHC1 dissociates UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74740 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Binding of SHC1 to insulin receptor'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-74740 Binding of SHC1 to insulin receptor UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74742 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylation of SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-74742 Phosphorylation of SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74743 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Dissociation of p-Y427-SHC1 from insulin receptor'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-74743 Dissociation of p-Y427-SHC1 from insulin receptor UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74746 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GRB2-1:SOS1 binds p-Y427-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-74746 GRB2-1:SOS1 binds p-Y427-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74748 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'De-phosphorylation of p-Y427-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-74748 De-phosphorylation of p-Y427-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-879925 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 bound to the common beta chain becomes tyrosine phosphorylated'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-879925 SHC1 bound to the common beta chain becomes tyrosine phosphorylated UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-879934 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of SHC1 is mediated by Y593 of the common beta chain'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-879934 Recruitment of SHC1 is mediated by Y593 of the common beta chain UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851888 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'MET binds SHC1-2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8851888 MET binds SHC1-2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851890 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'MET phosphorylates SHC1-2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8851890 MET phosphorylates SHC1-2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851899 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8851899 RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851900 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1-2 bound to MET recruits GRB2:SOS1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8851900 SHC1-2 bound to MET recruits GRB2:SOS1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853734 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction '2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8853734 2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853737 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction '2x p-5Y-RET:GDNF:GFRA complexes bind SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8853737 2x p-5Y-RET:GDNF:GFRA complexes bind SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853774 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'GAB in p-5Y-RET:GDNF:GFRA complexes is phosphorylated'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8853774 GAB in p-5Y-RET:GDNF:GFRA complexes is phosphorylated UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853793 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-5Y-RET complexes bind GRB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8853793 p-5Y-RET complexes bind GRB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8854897 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8854897 p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8854905 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-5Y-GAB in the RET-GRB2-GAB complexes binds p85-PI3K'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8854905 p-5Y-GAB in the RET-GRB2-GAB complexes binds p85-PI3K UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8854981 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 in the RET complex is phosphorylated'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8854981 SHC1 in the RET complex is phosphorylated UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8855508 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8855508 p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8934446 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Activated PKC phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8934446 Activated PKC phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8934465 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 binds PTPN12'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8934465 SHC1 binds PTPN12 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8983384 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3:p-Y-SHC1:GRB2 binds SOS1,SOS2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-8983384 IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3:p-Y-SHC1:GRB2 binds SOS1,SOS2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9029150 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'EPO:phospho-EPOR:phospho-JAK2:LYN:IRS2:phospho-CRKL:RAPGEF1:phospho-SHC1 binds GRB2:VAV1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9029150 EPO:phospho-EPOR:phospho-JAK2:LYN:IRS2:phospho-CRKL:RAPGEF1:phospho-SHC1 binds GRB2:VAV1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912527 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 mediates cytokine-induced phosphorylation of GAB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-912527 SHC1 mediates cytokine-induced phosphorylation of GAB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-913374 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated SHC1 recruits SHIP'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-913374 Phosphorylated SHC1 recruits SHIP UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-913424 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'The SHC1:SHIP1 complex is stabilized by GRB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-913424 The SHC1:SHIP1 complex is stabilized by GRB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9624014 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 is phosphorylated downstream of estrogen stimulation of GPER1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9624014 SHC1 is phosphorylated downstream of estrogen stimulation of GPER1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9624017 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-SHC1 binds integrin alpha5beta1:fibronectin'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9624017 p-SHC1 binds integrin alpha5beta1:fibronectin UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634390 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'ERBB2 homodimer phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9634390 ERBB2 homodimer phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634391 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'SHC1 binds phosphorylated ERBB2 homodimer'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9634391 SHC1 binds phosphorylated ERBB2 homodimer UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634402 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 homodimer'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9634402 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 homodimer UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634418 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9634418 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634584 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Estrogen receptor binds IGF1R and SHC1 in response to estrogen'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9634584 Estrogen receptor binds IGF1R and SHC1 in response to estrogen UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664950 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 KD mutants bind SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9664950 Phosphorylated heterodimers of ERBB2 KD mutants bind SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664976 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 KD mutants phosphorylate SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9664976 Phosphorylated heterodimers of ERBB2 KD mutants phosphorylate SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664983 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9664983 Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664991 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9664991 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665404 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. 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 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665406 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR phosphorylate SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665406 Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR phosphorylate SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665413 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR recruit GRB2:SOS1 through SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665413 Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR recruit GRB2:SOS1 through SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665416 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR bind SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665416 Phosphorylated heterodimers of ERBB2 ECD mutants and EGFR bind SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665699 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 TMD/JMD mutants recruit GRB2:SOS1 through SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665699 Phosphorylated heterodimers of ERBB2 TMD/JMD mutants recruit GRB2:SOS1 through SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665700 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665700 RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665701 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated ERBB2 TMD/JMD heterodimers bind SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665701 Phosphorylated ERBB2 TMD/JMD heterodimers bind SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9665705 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Phosphorylated heterodimers of ERBB2 TMD/JMD mutants phosphorylate SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9665705 Phosphorylated heterodimers of ERBB2 TMD/JMD mutants phosphorylate SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9674816 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9674816 p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700154 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Active ALK binds SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9700154 Active ALK binds SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700175 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'Active ALK phosphorylates SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9700175 Active ALK phosphorylates SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700190 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'ALK mutants bind SHC'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9700190 ALK mutants bind SHC UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700193 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'ALK mutants phosphorylate SHC1'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9700193 ALK mutants phosphorylate SHC1 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9724099 | ACCEPT | Summary: Reactome places SHC1 in the cytosol in the reaction 'ALK mutants:p-3Y SHC binds GRB2'. Reason: SHC1 is a cytosolic adaptor that is recruited from the cytosol to activated receptor complexes; the cytosolic location is correct. Supporting Evidence: Reactome:R-HSA-9724099 ALK mutants:p-3Y SHC binds GRB2 UniProt:P29353 SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of plasma membrane activity for the SHC family. Reason: SHC1 acts at the cytoplasmic face of the plasma membrane when bound to activated receptors; supported by human experimental data (PMID:14676841, PMID:9544989). Supporting Evidence: PMID:9544989 In cells expressing the wild-type receptor, Shc R397K, but not Shc R175K, translocated to the membrane in an EGF-dependent manner. |
| GO:0005886 plasma membrane | IDA PMID:14676841 Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc... | ACCEPT | Summary: SHC1 localises to the plasma membrane via its PTB domain after CD81 clustering. Reason: Direct observation of PTB-dependent plasma membrane recruitment, where SHC1 functions. Supporting Evidence: PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2404193 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'IGF1R phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-2404193 IGF1R phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2404195 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'IGF1,2:p-Y1161,1165,1166-IGF1R binds SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-2404195 IGF1,2:p-Y1161,1165,1166-IGF1R binds SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654402 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654402 Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654406 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR2:p-SHC1 binds GRB2:SOS1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654406 Activated FGFR2:p-SHC1 binds GRB2:SOS1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654407 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR2 phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654407 Activated FGFR2 phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654423 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR4:p-SHC1 binds GRB2:SOS1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654423 Activated FGFR4:p-SHC1 binds GRB2:SOS1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654426 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654426 Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654428 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR4 phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654428 Activated FGFR4 phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654582 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR1 phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654582 Activated FGFR1 phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654597 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR1:p-SHC1 binds GRB2:SOS1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654597 Activated FGFR1:p-SHC1 binds GRB2:SOS1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654600 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654600 Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654634 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR3 phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654634 Activated FGFR3 phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654646 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR3:p-SHC1 binds GRB2:SOS1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654646 Activated FGFR3:p-SHC1 binds GRB2:SOS1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654647 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5654647 Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'RAS GEFs promote RAS nucleotide exchange'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700175 | ACCEPT | Summary: Reactome places SHC1 at the plasma membrane (receptor-bound) in the reaction 'Active ALK phosphorylates SHC1'. Reason: Receptor-bound, phosphorylated SHC1 acts at the cytoplasmic face of the plasma membrane where it recruits GRB2-SOS to activate RAS. Supporting Evidence: Reactome:R-HSA-9700175 Active ALK phosphorylates SHC1 PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0005925 focal adhesion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Focal adhesion from UniProt subcellular location mapping. Reason: SHC1 participates in integrin/adhesion signalling and UniProt records focal adhesion localisation (PubMed:35687021); a real but context-dependent location. Supporting Evidence: UniProt:P29353 Cell junction, focal adhesion |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of EGFR signaling pathway participation. Reason: SHC1 is a direct component of the EGFR-SHC1-GRB2-SOS relay; strongly supported by human experiments. Supporting Evidence: PMID:9544989 In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway. |
| GO:0007173 epidermal growth factor receptor signaling pathway | TAS PMID:1623525 A novel transforming protein (SHC) with an SH2 domain is imp... | ACCEPT | Summary: SHC proteins complex with and are phosphorylated by activated EGFR. Reason: Core process; SHC1 carries the EGFR signal to GRB2-SOS-RAS. Supporting Evidence: PMID:1623525 These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of cell proliferation transferred from rat Shc1. Reason: SHC1 (p46/p52) propagates mitogenic RTK signals and SHC overexpression transforms fibroblasts; proliferation is a downstream outcome of its adaptor function rather than its core process. Supporting Evidence: PMID:1623525 NIH 3T3 mouse fibroblasts that constitutively overexpressed SHC acquired a transformed phenotype in culture and formed tumors in nude mice. |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:1623525 A novel transforming protein (SHC) with an SH2 domain is imp... | KEEP AS NON CORE | Summary: SHC overexpression transforms NIH 3T3 cells; SHC couples receptors to a proliferation pathway. Reason: Valid downstream outcome of mitogenic signalling; non-core relative to the receptor-adaptor function. Supporting Evidence: PMID:1623525 These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells. |
| GO:0008286 insulin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of insulin receptor signaling participation. Reason: SHC1 binds the autophosphorylated INSR NPEY motif and couples it to GRB2; the mouse GO-CAM insulin model uses Shc1 as the RTK adaptor. Supporting Evidence: PMID:8491186 The interactions between GRB2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH2 domain of GRB2 to phosphotyrosines on both IRS-1 and Shc. |
| GO:0008286 insulin receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Insulin receptor signaling transferred from rat Shc1. Reason: Consistent with direct human evidence of SHC1 binding INSR and recruiting GRB2 after insulin stimulation. Supporting Evidence: PMID:7537849 We conclude that SHC interacts directly with the IR and that phosphorylation of Tyr-960 within the IR juxtamembrane domain is necessary for efficient interaction. |
| GO:0030971 receptor tyrosine kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of receptor tyrosine kinase binding for the SHC family. Reason: SHC1 binds numerous activated RTKs (EGFR/ERBBs, INSR, IGF1R, TRKs, MET, KIT, ALK, EPHB1) via PTB/SH2 domains. Supporting Evidence: UniProt:P29353 Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. |
| GO:0030971 receptor tyrosine kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of receptor tyrosine kinase binding from mouse Shc1. Reason: Correct; see IBA row. Supporting Evidence: PMID:7541045 We conclude that SHC and IRS-1 interact with the tyrosine-phosphorylated NPEY motif of the IGFIR, and that both proteins interact via related motifs located in their amino termini. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (Shc-like PID domain) mapping to intracellular signal transduction. Reason: Broad but correct; SHC1 is an intracellular signalling adaptor. More specific RTK pathway terms are also present. Supporting Evidence: UniProt:P29353 Signaling adapter that couples activated growth factor receptors to signaling pathways. |
| GO:0042742 defense response to bacterium | IMP PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | MARK AS OVER ANNOTATED | Summary: SHC1 knockdown in Chlamydia-infected HeLa cells sensitises them to TNF-induced apoptosis. Reason: The full text shows SHC1 is exploited by the Chlamydia effector Tarp to promote early survival of the infected host cell; SHC1 is not needed for bacterial adhesion, invasion, inclusion formation or propagation. A pathogen-hijacked host survival pathway is not a host defense response to the bacterium; the phenotype is better captured by the negative regulation of apoptotic process row. Supporting Evidence: PMID:20624904 Furthermore, SHC1 is recruited immediately after infection, where it is not directly needed for adhesion, invasion, inclusion formation, or bacterial propagation PMID:20624904 SHC1 knockdown sensitized infected host cells to tumor necrosis factor-induced apoptosis. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | KEEP AS NON CORE | Summary: SHC1 knockdown sensitises Chlamydia-infected cells to TNF-induced apoptosis, showing SHC1 promotes survival. Reason: Supported by knockdown; anti-apoptotic survival signalling is a downstream output of SHC1-dependent pathways (context-dependent, and opposite for p66Shc). Supporting Evidence: PMID:20624904 SHC1 knockdown sensitized infected host cells to tumor necrosis factor-induced apoptosis. |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:14676841 Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc... | ACCEPT | Summary: SHC1 PTB-dependent membrane recruitment is required for CD81-induced ERK/MAPK activation. Reason: SHC1 positively regulates the MAPK (ERK) cascade by recruiting GRB2-SOS to activate RAS; the PTB mutant blocks ERK activation. Supporting Evidence: PMID:14676841 A mutant in the PTB domain of Shc failed to interact with phosphoinositides and localize to the plasma membrane thus blocking CD81-induced ERK/MAPKinase activation. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | MARK AS OVER ANNOTATED | Summary: Transcriptome analysis after SHC1 knockdown in Chlamydia-infected cells shows many genes up- and down-regulated. Reason: Genome-wide expression changes after knockdown of an upstream signalling adaptor are indirect consequences of altered signalling; SHC1 is not a transcriptional regulator. Supporting Evidence: PMID:20624904 Transcriptome analysis of SHC1-dependent gene regulation during infection indicated that SHC1 regulates apoptosis- and growth-related genes. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | MARK AS OVER ANNOTATED | Summary: Transcriptome analysis after SHC1 knockdown in Chlamydia-infected cells; more genes decrease than increase. Reason: Indirect effect of perturbing an upstream signalling adaptor; SHC1 does not act in transcription itself. Supporting Evidence: PMID:20624904 The observed approximately threefold increase of down-regulated genes as compared with up-regulated genes upon infection of SHC1 knockdown indicates a strong activating potential of SHC1 on gene expression |
| GO:0046875 ephrin receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of ephrin receptor binding from mouse Shc1. Reason: Supported by direct human evidence: activated EPHB1 recruits p52Shc (PMID:12925710). Supporting Evidence: PMID:12925710 Here we demonstrate that activated EphB1 recruits the adaptor proteins Grb2 and p52Shc and promotes p52Shc and c-Src tyrosine phosphorylation as well as MAPK/extracellular signal-regulated kinase (ERK) activation. |
| GO:0046875 ephrin receptor binding | IPI PMID:12925710 EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and pro... | ACCEPT | Summary: Activated EPHB1 recruits p52Shc; EphB1 Tyr600/Tyr778 are required and Src-phosphorylated p52Shc joins EphB1 complexes via its PTB domain. Reason: Direct experimental evidence for SHC1 binding an activated Eph receptor tyrosine kinase, leading to MAPK/ERK activation. Supporting Evidence: PMID:12925710 Site-directed mutagenesis experiments demonstrate that tyrosines 600 and 778 of EphB1 are required for its interaction with c-Src and p52Shc. |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of IGF receptor signaling pathway from mouse Shc1. Reason: SHC1 binds the phosphorylated IGF1R NPEY motif and is phosphorylated downstream of IGF1R (Reactome IGF1R phosphorylates SHC1). Supporting Evidence: PMID:7541045 Insulin receptor substrate-1 (IRS-1) and SHC become rapidly phosphorylated upon tyrosines after insulin-like growth factor I receptor (IGFIR) activation. |
| GO:0048408 epidermal growth factor binding | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of epidermal growth factor binding from mouse Shc1. Reason: SHC1 binds the EGF receptor, not the EGF ligand. The mouse source annotation (IPI, PMID:15467833) has mouse Egfr (Q01279) as its WITH/FROM partner, so the intended assertion is EGF receptor binding; replace with GO:0005154. Proposed replacements: epidermal growth factor receptor binding Supporting Evidence: PMID:8034616 These results indicate that tyrosine 1148 of activated human EGF receptors is a major binding site of Shc and tyrosine 1173 is a secondary binding site in intact cells. |
| GO:0070435 Shc-EGFR complex | ISS GO_REF:0000024 | ACCEPT | Summary: Shc-EGFR complex transferred from rat Shc1. Reason: SHC1 forms a complex with the activated EGFR via its PTB and SH2 domains, as demonstrated in human cells. Supporting Evidence: PMID:9544989 The present results indicate that tyrosine 1148 of the activated EGF receptor mainly interacts with the Shc PTB domain in intact cells. |
| GO:0071363 cellular response to growth factor stimulus | IDA PMID:20010870 Copine-III interacts with ErbB2 and promotes tumor cell migr... | KEEP AS NON CORE | Summary: Growth factor (heregulin)-stimulated ErbB2 signalling assays in the Copine-III study. Reason: Correct but very broad; SHC1 responds to growth factor stimulation as part of RTK signalling. The more specific RTK pathway terms carry the core information. Supporting Evidence: PMID:20010870 In breast cancer cells, Copine-III requires Ca(2+) for binding to the plasma membrane, where it interacts with ErbB2 upon receptor stimulation, an interaction that is dependent on receptor activity. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Is p66Shc a genuine redox enzyme (cytochrome c-dependent H2O2 production) or a stress-regulated adaptor that controls ROS indirectly, and should human SHC1 carry an isoform-specific (P29353-1) oxidative-stress process annotation such as cellular response to oxidative stress?
Q: Where does stress-activated p66Shc act: the mitochondrial intermembrane space or mitochondria-associated ER membranes? This determines which isoform-specific cellular component annotations are appropriate.
Q: Should the Reactome-derived plasma membrane annotations be restricted to the receptor-bound, phosphorylated p46/p52 pool, given that most SHC1 is cytosolic at steady state?
Experiment: Isoform-specific CRISPR knock-in in human cells (p66-null, p46/p52-null, and Y239/240/317F CH1 mutant) with rescue, measuring GRB2 recruitment, RAS-GTP and ERK kinetics after EGF, to separate adaptor activity of each isoform.
Type: genetic perturbation with signalling readout
Experiment: In vitro reconstitution of purified human p66Shc CH2/PTB with cytochrome c and redox-dead (E132Q/E133Q) mutants, measuring H2O2 production, to test whether p66Shc has intrinsic redox activity.
Type: biochemical reconstitution
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)