Src (pp60c-src) is the rat proto-oncogene non-receptor protein tyrosine kinase, the founding member of the Src family. It has an N-terminal myristoylated unique region, SH3 and SH2 domains and a C-terminal tyrosine kinase domain; it is held inactive by CSK phosphorylation of Tyr530 and SH2/SH3 intramolecular engagement, and is activated by dephosphorylation of Tyr530 and autophosphorylation of Tyr419. Anchored at the cytoplasmic face of the plasma membrane, Src is recruited to integrin, receptor tyrosine kinase, G protein-coupled receptor (for example angiotensin II AT1) and cytokine receptor complexes, where it phosphorylates receptors, focal adhesion proteins (FAK, paxillin), junctional proteins and signalling enzymes, relaying signals to the Ras-MAP kinase and PI3K-Akt pathways that control adhesion, migration, proliferation and survival. In neurons, where the N1-Src and N2-Src splice isoforms are also expressed, Src is anchored to the NMDA receptor complex through ND2 and PSD-95 at glutamatergic synapses and up-regulates NMDA receptor channel activity. Additional pools act at caveolae, endosomes and brain mitochondria, and Src is required for osteoclastic bone resorption.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: ISO from human SRC (IMP, PMID:21531765). Src is a membrane-associated signalling kinase; any repression of RNA polymerase II transcription is an indirect downstream consequence of signalling through transcription factors. Reason: Src does not act on the transcription machinery; downstream gene-expression effects are better captured by its signalling roles. Annotating a direct negative transcription-regulation process to a cytoplasmic/membrane tyrosine kinase over-extends the donor phenotype. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P12931 · human SRC SUPPORTS SOURCE BUT NOT TARGET Donor carries this term with experimental support; the concern is the scope of the term for a signalling kinase, not the donor evidence. Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0001819 positive regulation of cytokine production | IMP PMID:19736311 Src-dependent STAT-3-mediated expression of monocyte chemoat... | KEEP AS NON CORE | Summary: Rat VSMC study: 15(S)-HETE induced MCP-1 expression via Src-STAT-3 signalling. Reason: Src kinase activity is required upstream of STAT-3 for MCP-1 expression; a valid but context-specific downstream outcome of its signalling role. Supporting Evidence: PMID:19736311 15(S)-HETE also induced monocyte chemoattractant protein-1 (MCP-1) expression via Src-STAT-3 signaling |
| GO:0002102 podosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src. Src is required for podosome formation and localizes there. Reason: Podosome localization is well established for Src in osteoclasts and transformed cells; peripheral to the core function. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Required for podosome formation |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic protein kinase activity. Src is a tyrosine-specific, non-receptor kinase. Reason: Correct but less specific than the evidence supports. The gene already carries GO:0004715 non-membrane spanning protein tyrosine kinase activity (IBA, IEA, ISO), a descendant of protein kinase activity; replace with that term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProtKB:Q9WUD9 PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Generic protein kinase activity. Src is a tyrosine-specific, non-receptor kinase. Reason: Correct but less specific than the evidence supports. The gene already carries GO:0004715 non-membrane spanning protein tyrosine kinase activity (IBA, IEA, ISO), a descendant of protein kinase activity; replace with that term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98397 · mouse Src SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProtKB:Q9WUD9 PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Generic protein kinase activity. Src is a tyrosine-specific, non-receptor kinase. Reason: Correct but less specific than the evidence supports. The gene already carries GO:0004715 non-membrane spanning protein tyrosine kinase activity (IBA, IEA, ISO), a descendant of protein kinase activity; replace with that term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProtKB:Q9WUD9 PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:26026271 The N2-Src neuronal splice variant of C-Src has altered SH3 ... | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:28220894 Inhibition of N1-Src kinase by a specific SH3 peptide ligand... | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:12488346 pp60c-Src Kinase mediates growth effects of the full-length ... | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:8849729 A role for Pyk2 and Src in linking G-protein-coupled recepto... | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98397 · mouse Src SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-RNO-548972 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-RNO-9037056 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-RNO-9612145 | MODIFY | Summary: Protein tyrosine kinase activity is the defining activity of Src; rat data show kinase activity of the c-Src, N1-Src and N2-Src isoforms and of endogenous c-Src in several rat cell systems. Reason: The activity is correct and core, but Src is a cytoplasmic, myristoyl-anchored kinase without a transmembrane segment, so the more specific GO:0004715 non-membrane spanning protein tyrosine kinase activity (a descendant of GO:0004713, already on this gene by IBA/IEA/ISO) is the right core term. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Src is the prototypical non-receptor (non-membrane spanning) protein tyrosine kinase. Reason: Core molecular function, supported by family membership, the catalytic domain with proton acceptor Asp389, and rat kinase assays (PMID:26026271, PMID:8849729, PMID:12488346). Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Src is the prototypical non-receptor (non-membrane spanning) protein tyrosine kinase. Reason: Core molecular function, supported by family membership, the catalytic domain with proton acceptor Asp389, and rat kinase assays (PMID:26026271, PMID:8849729, PMID:12488346). Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Src is the prototypical non-receptor (non-membrane spanning) protein tyrosine kinase. Reason: Core molecular function, supported by family membership, the catalytic domain with proton acceptor Asp389, and rat kinase assays (PMID:26026271, PMID:8849729, PMID:12488346). Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. PMID:26026271 N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. |
| GO:0005080 protein kinase C binding | IPI PMID:14751567 Interaction of estrogen receptor alpha with protein kinase C... | KEEP AS NON CORE | Summary: Co-immunoprecipitation of rat Src with PKCalpha (osteoblasts) and PKCdelta (skeletal muscle). Reason: The interactions are reported in rat cells and have regulatory consequences (PKC phosphorylates Src; Src regulates PKCdelta), but they are context-specific partner interactions rather than a core activity. Supporting Evidence: PMID:14751567 PKCalpha from over-confluent cells phosphorylated p60c-Src in vitro, suggesting functional interaction between the two kinases. PMID:15337529 Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta. PMID:19952103 Thus, the regulatory domain of PKCdelta via interaction with Src appears to determine the role of PKCdelta as a positive regulator of IR signaling in skeletal muscle. |
| GO:0005080 protein kinase C binding | IPI PMID:15337529 Src tyrosine kinase regulates insulin-induced activation of ... | KEEP AS NON CORE | Summary: Co-immunoprecipitation of rat Src with PKCalpha (osteoblasts) and PKCdelta (skeletal muscle). Reason: The interactions are reported in rat cells and have regulatory consequences (PKC phosphorylates Src; Src regulates PKCdelta), but they are context-specific partner interactions rather than a core activity. Supporting Evidence: PMID:14751567 PKCalpha from over-confluent cells phosphorylated p60c-Src in vitro, suggesting functional interaction between the two kinases. PMID:15337529 Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta. PMID:19952103 Thus, the regulatory domain of PKCdelta via interaction with Src appears to determine the role of PKCdelta as a positive regulator of IR signaling in skeletal muscle. |
| GO:0005080 protein kinase C binding | IPI PMID:19952103 The regulatory domain of protein kinase C delta positively r... | KEEP AS NON CORE | Summary: Co-immunoprecipitation of rat Src with PKCalpha (osteoblasts) and PKCdelta (skeletal muscle). Reason: The interactions are reported in rat cells and have regulatory consequences (PKC phosphorylates Src; Src regulates PKCdelta), but they are context-specific partner interactions rather than a core activity. Supporting Evidence: PMID:14751567 PKCalpha from over-confluent cells phosphorylated p60c-Src in vitro, suggesting functional interaction between the two kinases. PMID:15337529 Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta. PMID:19952103 Thus, the regulatory domain of PKCdelta via interaction with Src appears to determine the role of PKCdelta as a positive regulator of IR signaling in skeletal muscle. |
| GO:0005102 signaling receptor binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Src family kinases are recruited to and bind the cytoplasmic domains of many receptors (integrins, RTKs, GPCR-associated complexes, NMDA receptors). Reason: True of Src and its family (PAINT places it at the SFK node); receptor binding underlies recruitment of Src to receptor complexes but is a means to its kinase function rather than a core activity. Kept as non-core; more specific receptor-binding rows exist for individual partners. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. PMID:11478920 Src and Pyk2 co-immunoprecipitated with NR2A and the binding increased after I/R |
| GO:0005102 signaling receptor binding | IPI PMID:11478920 NMDA receptor activation results in tyrosine phosphorylation... | KEEP AS NON CORE | Summary: Src family kinases are recruited to and bind the cytoplasmic domains of many receptors (integrins, RTKs, GPCR-associated complexes, NMDA receptors). Reason: True of Src and its family (PAINT places it at the SFK node); receptor binding underlies recruitment of Src to receptor complexes but is a means to its kinase function rather than a core activity. Kept as non-core; more specific receptor-binding rows exist for individual partners. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. PMID:11478920 Src and Pyk2 co-immunoprecipitated with NR2A and the binding increased after I/R |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src family kinases are recruited to and bind the cytoplasmic domains of many receptors (integrins, RTKs, GPCR-associated complexes, NMDA receptors). Reason: True of Src and its family (PAINT places it at the SFK node); receptor binding underlies recruitment of Src to receptor complexes but is a means to its kinase function rather than a core activity. Kept as non-core; more specific receptor-binding rows exist for individual partners. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. PMID:11478920 Src and Pyk2 co-immunoprecipitated with NR2A and the binding increased after I/R |
| GO:0005158 insulin receptor binding | IPI PMID:19952103 The regulatory domain of protein kinase C delta positively r... | KEEP AS NON CORE | Summary: Src associates with the insulin receptor in rat skeletal muscle cells. Reason: Supported co-IP evidence in rat myotubes; a context-specific partner interaction. Supporting Evidence: PMID:19952103 Binding of Src to IR was decreased in PKCalpha/delta cells but remained elevated in the PKCdelta/alpha cells in response to insulin. PMID:15337529 Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta. |
| GO:0005178 integrin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC. Src binds integrin beta cytoplasmic tails and is activated by integrin engagement. Reason: Plausible for rat Src; integrin association is part of its recruitment to adhesion complexes. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0005515 protein binding | IPI PMID:12023880 Interaction of protein tyrosine phosphatase (PTP) 1B with it... | REMOVE | Summary: Bare protein binding. PTP1B interaction study; PTP1B activates Src family kinases. Reason: Uninformative per the protein-binding policy; removal does not dispute that the interaction occurs. Informative partner-specific terms are retained elsewhere in this review. Supporting Evidence: PMID:12023880 both the C-terminal proline-rich region and the tandem tyrosine residues present in the N-terminal region are required for the activation of Src family kinases. |
| GO:0005515 protein binding | IPI PMID:12526090 Interaction between chicken protein tyrosine phosphatase 1 (... | REMOVE | Summary: Bare protein binding. Rat PTP1 binds v-src in transformed Rat-1 fibroblasts. Reason: Uninformative per the protein-binding policy; removal does not dispute that the interaction occurs. Informative partner-specific terms are retained elsewhere in this review. Supporting Evidence: PMID:12526090 Here we show that CPTP1-like rat PTP1 binds to p60(v-src) in vivo |
| GO:0005515 protein binding | IPI PMID:16352297 Evidence for multiple Src binding sites on the alpha1c L-typ... | MODIFY | Summary: Bare protein binding. Src binds the alpha1c L-type Ca2+ channel subunit. Reason: The paper maps Src SH3 binding sites on the alpha1c (Cav1.2) channel subunit, an ion channel whose activity Src modulates. Replace bare protein binding with GO:0044325 transmembrane transporter binding, which the gene also carries from rat channel studies. Proposed replacements: transmembrane transporter binding Supporting Evidence: PMID:16352297 Src binds to both the II-III linker and C-terminal tail regions of the alpha1c subunit to differentially modulate channel activity. |
| GO:0005515 protein binding | IPI PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | REMOVE | Summary: Bare protein binding. Mesangial cell PDGF signalling study. Reason: Uninformative per the protein-binding policy; removal does not dispute that the interaction occurs. Informative partner-specific terms are retained elsewhere in this review. Supporting Evidence: PMID:16530387 These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. |
| GO:0005515 protein binding | IPI PMID:18211905 Expression of tetraspan protein CD63 activates protein-tyros... | REMOVE | Summary: Bare protein binding. c-Src co-immunoprecipitates with RPTPalpha and CD63 in rat kidney. Reason: Uninformative per the protein-binding policy; removal does not dispute that the interaction occurs. Informative partner-specific terms are retained elsewhere in this review. Supporting Evidence: PMID:18211905 c-Src was coimmunoprecipitated with RPTPalpha and CD63 both in 293T cells transfected with CD63 and in lysates prepared from native rat kidney. |
| GO:0005515 protein binding | IPI PMID:31585087 Oncogenic Mutations Rewire Signaling Pathways by Switching P... | REMOVE | Summary: Bare protein binding. Phosphotyrosine interaction proteomics in lung tissue. Reason: Uninformative per the protein-binding policy; removal does not dispute that the interaction occurs. Informative partner-specific terms are retained elsewhere in this review. Supporting Evidence: PMID:31585087 we determined their recruited protein signaling complexes in lung tissue by interaction proteomics. |
| GO:0005515 protein binding | IPI PMID:8849729 A role for Pyk2 and Src in linking G-protein-coupled recepto... | MODIFY | Summary: Bare protein binding. Src SH2 domain binds Pyk2 phosphotyrosine 402. Reason: The interaction is informative: the Src SH2 domain binds phosphorylated Tyr402 of Pyk2 (PTK2B). Replace bare protein binding with GO:0001784 phosphotyrosine residue binding. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:8849729 tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding by the kinase domain (InterPro/PROSITE kinase ATP-binding signature). Reason: Correct; ATP is the phosphate donor of the kinase reaction. ATP binding is a component of the kinase activity rather than a separate function. Supporting Evidence: UniProtKB:Q9WUD9 PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization reported for Src orthologs (UniProt, by similarity to mouse). Reason: A minor pool of Src is reported in the nucleus; peripheral to its membrane-associated signalling function. Supporting Evidence: UniProtKB:Q9WUD9 Nucleus {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nuclear localization reported for Src orthologs (UniProt, by similarity to mouse). Reason: A minor pool of Src is reported in the nucleus; peripheral to its membrane-associated signalling function. Supporting Evidence: UniProtKB:Q9WUD9 Nucleus {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nuclear localization reported for Src orthologs (UniProt, by similarity to mouse). Reason: A minor pool of Src is reported in the nucleus; peripheral to its membrane-associated signalling function. Supporting Evidence: UniProtKB:Q9WUD9 Nucleus {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nuclear localization reported for Src orthologs (UniProt, by similarity to mouse). Reason: A minor pool of Src is reported in the nucleus; peripheral to its membrane-associated signalling function. Supporting Evidence: UniProtKB:Q9WUD9 Nucleus {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. |
| GO:0005737 cytoplasm | IDA PMID:10698670 Rat testicular Src: normal distribution and involvement in e... | KEEP AS NON CORE | Summary: Src is a cytoplasmic protein (peripheral on the cytoplasmic face of membranes); rat testis immunostaining shows Sertoli cell cytoplasm. Reason: Correct, and as precise as the immunostaining and fractionation assays allow; the functional pool acts at the cytoplasmic face of the plasma membrane, which is captured by the plasma membrane rows. Supporting Evidence: PMID:10698670 In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Src is a cytoplasmic protein (peripheral on the cytoplasmic face of membranes); rat testis immunostaining shows Sertoli cell cytoplasm. Reason: Correct, and as precise as the immunostaining and fractionation assays allow; the functional pool acts at the cytoplasmic face of the plasma membrane, which is captured by the plasma membrane rows. Supporting Evidence: PMID:10698670 In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src is a cytoplasmic protein (peripheral on the cytoplasmic face of membranes); rat testis immunostaining shows Sertoli cell cytoplasm. Reason: Correct, and as precise as the immunostaining and fractionation assays allow; the functional pool acts at the cytoplasmic face of the plasma membrane, which is captured by the plasma membrane rows. Supporting Evidence: PMID:10698670 In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src is a cytoplasmic protein (peripheral on the cytoplasmic face of membranes); rat testis immunostaining shows Sertoli cell cytoplasm. Reason: Correct, and as precise as the immunostaining and fractionation assays allow; the functional pool acts at the cytoplasmic face of the plasma membrane, which is captured by the plasma membrane rows. Supporting Evidence: PMID:10698670 In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial localization. Rat brain mitochondria contain Src, which is activated there by ATP and regulates oxidative phosphorylation complexes. Reason: Root-organelle check: the organelle claim holds for rat independently of the donors, from purified rat brain mitochondria (PMID:12007793, PMID:18583343, PMID:21063895). Peripheral to the core plasma-membrane signalling function, so non-core. Supporting Evidence: PMID:18583343 An immunodetection study of protein tyrosine phosphatase 1B (PTP-1B), SHP-2, and Src in isolated mitochondria from different rat tissues (brain, muscle, heart, liver, and kidney) revealed their exclusive localization in the brain. PMID:12007793 Immunoblotting and immunoprecipitation assays of mitochondrial lysates confirmed the presence of Fyn, Src and Lyn kinases PMID:21063895 Our analysis emphasizes the regulatory function of Src and its modulation by PTP1B on oxidative phosphorylation in mitochondria. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial localization. Rat brain mitochondria contain Src, which is activated there by ATP and regulates oxidative phosphorylation complexes. Reason: Root-organelle check: the organelle claim holds for rat independently of the donors, from purified rat brain mitochondria (PMID:12007793, PMID:18583343, PMID:21063895). Peripheral to the core plasma-membrane signalling function, so non-core. Supporting Evidence: PMID:18583343 An immunodetection study of protein tyrosine phosphatase 1B (PTP-1B), SHP-2, and Src in isolated mitochondria from different rat tissues (brain, muscle, heart, liver, and kidney) revealed their exclusive localization in the brain. PMID:12007793 Immunoblotting and immunoprecipitation assays of mitochondrial lysates confirmed the presence of Fyn, Src and Lyn kinases PMID:21063895 Our analysis emphasizes the regulatory function of Src and its modulation by PTP1B on oxidative phosphorylation in mitochondria. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial localization. Rat brain mitochondria contain Src, which is activated there by ATP and regulates oxidative phosphorylation complexes. Reason: Root-organelle check: the organelle claim holds for rat independently of the donors, from purified rat brain mitochondria (PMID:12007793, PMID:18583343, PMID:21063895). Peripheral to the core plasma-membrane signalling function, so non-core. Supporting Evidence: PMID:18583343 An immunodetection study of protein tyrosine phosphatase 1B (PTP-1B), SHP-2, and Src in isolated mitochondria from different rat tissues (brain, muscle, heart, liver, and kidney) revealed their exclusive localization in the brain. PMID:12007793 Immunoblotting and immunoprecipitation assays of mitochondrial lysates confirmed the presence of Fyn, Src and Lyn kinases PMID:21063895 Our analysis emphasizes the regulatory function of Src and its modulation by PTP1B on oxidative phosphorylation in mitochondria. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane localization transferred from mouse/human Src (UniProt, by similarity). Reason: Src in mitochondria regulates cytochrome c oxidase; rat brain mitochondrial Src is membrane-associated in the intermembrane space region (PMID:12007793). Plausible but peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0005743 mitochondrial inner membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane localization transferred from mouse/human Src (UniProt, by similarity). Reason: Src in mitochondria regulates cytochrome c oxidase; rat brain mitochondrial Src is membrane-associated in the intermembrane space region (PMID:12007793). Plausible but peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0005743 mitochondrial inner membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane localization transferred from mouse/human Src (UniProt, by similarity). Reason: Src in mitochondria regulates cytochrome c oxidase; rat brain mitochondrial Src is membrane-associated in the intermembrane space region (PMID:12007793). Plausible but peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane localization transferred from mouse/human Src (UniProt, by similarity). Reason: Src in mitochondria regulates cytochrome c oxidase; rat brain mitochondrial Src is membrane-associated in the intermembrane space region (PMID:12007793). Plausible but peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane localization transferred from mouse/human Src (UniProt, by similarity). Reason: Src in mitochondria regulates cytochrome c oxidase; rat brain mitochondrial Src is membrane-associated in the intermembrane space region (PMID:12007793). Plausible but peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0005764 lysosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: lysosome. Src traffics through the endosomal pathway. Reason: Root-organelle check: the human donor reports Src on late endosomes/lysosomes; consistent with endosomal trafficking of activated Src seen in rat fibroblasts (PMID:19193640, Rab11 endosomes). Non-core. Supporting Evidence: PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005770 late endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: late endosome. Reason: Src cycles through endosomal compartments after activation; plausible for rat and peripheral to the core function. Supporting Evidence: PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytosolic pool of Src. Reason: Inactive Src exists partly in the cytosol and on intracellular membranes; correct but peripheral to the membrane-associated active pool. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. |
| GO:0005829 cytosol | NAS PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: Cytosolic pool of Src. Reason: Inactive Src exists partly in the cytosol and on intracellular membranes; correct but peripheral to the membrane-associated active pool. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-548972 | KEEP AS NON CORE | Summary: Cytosolic pool of Src. Reason: Inactive Src exists partly in the cytosol and on intracellular membranes; correct but peripheral to the membrane-associated active pool. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoskeleton localization (UniProt by similarity); Src binds AFAP1 and localizes to actin filaments. Reason: Plausible; association with the actin cytoskeleton is downstream of substrate phosphorylation. Non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. |
| GO:0005856 cytoskeleton | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytoskeleton localization (UniProt by similarity); Src binds AFAP1 and localizes to actin filaments. Reason: Plausible; association with the actin cytoskeleton is downstream of substrate phosphorylation. Non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. |
| GO:0005856 cytoskeleton | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cytoskeleton localization (UniProt by similarity); Src binds AFAP1 and localizes to actin filaments. Reason: Plausible; association with the actin cytoskeleton is downstream of substrate phosphorylation. Non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P05480} UniProtKB:Q9WUD9 Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. |
| GO:0005884 actin filament | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: actin filament. Reason: Src localizes to actin filaments via AFAP1. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | TAS Reactome:R-RNO-8937895 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | TAS Reactome:R-RNO-8937915 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | TAS Reactome:R-RNO-9037056 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005886 plasma membrane | TAS Reactome:R-RNO-9612145 | ACCEPT | Summary: Src is N-myristoylated and anchored to the cytoplasmic face of the plasma membrane, where receptor engagement activates it. Reason: Core location of the active kinase; myristoylation is essential for membrane targeting, and v-Src/c-Src plasma membrane targeting is seen in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0005901 caveola | IDA PMID:20167931 Regulation of coronary arterial BK channels by caveolae-medi... | KEEP AS NON CORE | Summary: Src colocalizes with BK channels, AT1 receptor and NOX-1 in caveolae of rat arterial smooth muscle cells. Reason: Direct rat evidence for caveolar localization; caveolae are a specialized plasma membrane domain where a fraction of Src acts. Non-core relative to the general plasma membrane location. Supporting Evidence: PMID:20167931 c-Src kinases (c-Src) were colocalized in the caveolae of rat arterial smooth muscle cells |
| GO:0005901 caveola | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Src colocalizes with BK channels, AT1 receptor and NOX-1 in caveolae of rat arterial smooth muscle cells. Reason: Direct rat evidence for caveolar localization; caveolae are a specialized plasma membrane domain where a fraction of Src acts. Non-core relative to the general plasma membrane location. Supporting Evidence: PMID:20167931 c-Src kinases (c-Src) were colocalized in the caveolae of rat arterial smooth muscle cells |
| GO:0005901 caveola | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src colocalizes with BK channels, AT1 receptor and NOX-1 in caveolae of rat arterial smooth muscle cells. Reason: Direct rat evidence for caveolar localization; caveolae are a specialized plasma membrane domain where a fraction of Src acts. Non-core relative to the general plasma membrane location. Supporting Evidence: PMID:20167931 c-Src kinases (c-Src) were colocalized in the caveolae of rat arterial smooth muscle cells |
| GO:0005901 caveola | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src colocalizes with BK channels, AT1 receptor and NOX-1 in caveolae of rat arterial smooth muscle cells. Reason: Direct rat evidence for caveolar localization; caveolae are a specialized plasma membrane domain where a fraction of Src acts. Non-core relative to the general plasma membrane location. Supporting Evidence: PMID:20167931 c-Src kinases (c-Src) were colocalized in the caveolae of rat arterial smooth muscle cells |
| GO:0005911 cell-cell junction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell-cell junction localization; Src acts at adherens and gap junctions. Reason: Supported by the junctional substrates (catenins, connexin-43); a real but secondary site of action. Supporting Evidence: UniProtKB:Q9WUD9 SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). UniProtKB:Q9WUD9 Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). |
| GO:0005911 cell-cell junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cell-cell junction localization; Src acts at adherens and gap junctions. Reason: Supported by the junctional substrates (catenins, connexin-43); a real but secondary site of action. Supporting Evidence: UniProtKB:Q9WUD9 SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). UniProtKB:Q9WUD9 Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). |
| GO:0005925 focal adhesion | IEA GO_REF:0000044 | ACCEPT | Summary: Src localizes to focal adhesions after integrin engagement and phosphorylates FAK and paxillin there. Reason: Core site of Src action in integrin signalling; supported by curated UniProt and by active Src at focal adhesions in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0005925 focal adhesion | ISO GO_REF:0000121 | ACCEPT | Summary: Src localizes to focal adhesions after integrin engagement and phosphorylates FAK and paxillin there. Reason: Core site of Src action in integrin signalling; supported by curated UniProt and by active Src at focal adhesions in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0005925 focal adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: Src localizes to focal adhesions after integrin engagement and phosphorylates FAK and paxillin there. Reason: Core site of Src action in integrin signalling; supported by curated UniProt and by active Src at focal adhesions in rat fibroblasts (PMID:19193640). Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0007155 cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cell adhesion (IBA, family-level; ARBA IEA). Reason: Src family kinases regulate cell adhesion through phosphorylation of focal adhesion and junctional proteins; a valid process-level role, kept as non-core. Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) PMID:15735685 indicating that r-PTPeta regulates cell-substratum adhesion by activating c-Src. |
| GO:0007155 cell adhesion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cell adhesion (IBA, family-level; ARBA IEA). Reason: Src family kinases regulate cell adhesion through phosphorylation of focal adhesion and junctional proteins; a valid process-level role, kept as non-core. Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) PMID:15735685 indicating that r-PTPeta regulates cell-substratum adhesion by activating c-Src. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Src acts in EGFR signalling (EGFR internalization, downstream Akt). Rat hepatocyte TGF-beta1 study shows EGFR-dependent c-Src activation required for Akt. Reason: Real participation (Src is recruited to and phosphorylates the activated receptor complex), but one of many receptor pathways in which Src acts. Supporting Evidence: UniProtKB:Q9WUD9 Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) PMID:15856020 The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEP PMID:15856020 Involvement of EGF receptor and c-Src in the survival signal... | KEEP AS NON CORE | Summary: Src acts in EGFR signalling (EGFR internalization, downstream Akt). Rat hepatocyte TGF-beta1 study shows EGFR-dependent c-Src activation required for Akt. Reason: Real participation (Src is recruited to and phosphorylates the activated receptor complex), but one of many receptor pathways in which Src acts. Supporting Evidence: UniProtKB:Q9WUD9 Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) PMID:15856020 The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: TGF-beta receptor signalling. Reason: Src participates in TGF-beta-induced signalling (e.g. EGFR transactivation in rat hepatocytes, PMID:15856020). The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: PMID:15856020 The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. |
| GO:0007229 integrin-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Src is a central transducer of integrin signalling: recruited to activated integrins, it phosphorylates FAK and paxillin. Reason: Core process for Src; ISO from human is supported by curated UniProt text and rat evidence that integrin antagonism prevents Src activation (PMID:14985360). Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) PMID:14985360 Infusion of the integrin-antagonizing hexapeptide GRGDSP or the Src inhibitor PP-2 prevented activation of Src and p38(MAPK) and, consequently, proteolysis inhibition by insulin. |
| GO:0007276 gamete generation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Gamete generation by ARBA rule. Reason: Rests on expression of Src in testis/spermatids and on pharmacological studies; Src is not known to perform a step of gametogenesis. Over-annotation. Supporting Evidence: PMID:7530000 The immunohistochemical staining of pp60c-src in rat testes demonstrated that pp60c-src is most abundantly expressed in the spermatids which are the spermatogenic cells in the post-meiotic phase of the spermatogenesis. |
| GO:0007283 spermatogenesis | IEP PMID:7530000 pp60c-src expression in rat spermatogenesis. | MARK AS OVER ANNOTATED | Summary: IEP: pp60c-src expression and kinase activity peak in rat testis at the onset of meiosis; strongest in spermatids. Reason: Expression timing alone does not show that Src performs a step of spermatogenesis. Over-annotation from expression data. Supporting Evidence: PMID:7530000 The immunohistochemical staining of pp60c-src in rat testes demonstrated that pp60c-src is most abundantly expressed in the spermatids which are the spermatogenic cells in the post-meiotic phase of the spermatogenesis. |
| GO:0007595 lactation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: lactation. Reason: Derived from mouse phenotypes; a physiological context downstream of Src signalling in mammary epithelium. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0007611 learning or memory | IEP PMID:10884433 Nonreceptor tyrosine protein kinase pp60c-src in spatial lea... | MARK AS OVER ANNOTATED | Summary: IEP: c-src mRNA and synaptic Src activity increase after spatial learning in rat hippocampus. Reason: The cited paper is correlative (expression/activity changes after training). The mechanistic role of Src in synaptic plasticity is captured by NMDA receptor regulation; an organism-level learning term from expression data is over-annotation. Supporting Evidence: PMID:10884433 After spatial maze learning, up-regulation of c-src mRNA was observed in the CA3 region of the hippocampus PMID:10884433 Training also triggered an increase in c-src protein tyrosine kinase activity that was correlated with its tyrosine dephosphorylation in the synaptic membrane fraction. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: IMP: c-Src inhibition blocks PDGF-induced DNA synthesis and proliferation in rat mesangial cells. Reason: Supported downstream outcome of Src signalling; non-core. Supporting Evidence: PMID:16530387 A pharmacologic inhibitor of c-Src, PP1, blocked PDGF-induced DNA synthesis with concomitant inhibition of c-Src phosphorylation. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:20149623 Butyrate reduced lipopolysaccharide-mediated macrophage migr... | MARK AS OVER ANNOTATED | Summary: IEP: butyrate suppresses LPS-induced Src expression in macrophages. Reason: A change in Src transcript level in response to a compound is an expression pattern, not evidence that Src performs part of a xenobiotic response. Supporting Evidence: PMID:20149623 LPS-mediated Src induction was greatly suppressed by butyrate and that could be attributable to reduced level of the src transcript. |
| GO:0009612 response to mechanical stimulus | IEP PMID:15731459 Caveolin-1 facilitates mechanosensitive protein kinase B (Ak... | KEEP AS NON CORE | Summary: IEP: cyclic stretch activates Src in rat VSMC; kinase-dead c-Src prevents mechanosensitive PI3K/Akt activation. Reason: The abstract includes perturbation evidence that Src is required for the stretch response; valid non-core context. Supporting Evidence: PMID:15731459 PI3-K and Akt were resistant to activation when Src kinases were inhibited pharmacologically or by overexpression of a kinase-dead c-Src mutant. |
| GO:0010447 response to acidic pH | IEP PMID:12081562 Role of c-SRC and ERK in acid-induced activation of NHE3. | KEEP AS NON CORE | Summary: IEP: acid incubation and in vivo acidosis activate renal c-Src; dominant-negative c-Src blocks acid-induced NHE3 activation. Reason: Supported as a context-specific signalling role (the cell-line experiments used OKP cells; the in vivo activation was in rat kidney). Non-core. Supporting Evidence: PMID:12081562 Acidosis in vivo also activated renal cortical c-Src and ERK kinases PMID:12081562 Expression of dominant negative c-srcK295M in OKP cells prevented acid-induced activation of NHE3. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Src signalling increases expression of target genes (c-fos, MMP-9, COX-2) in rat cells. Reason: Supported indirect downstream outcome of the kinase; non-core. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:19763735 LTA induced MMP-9 expression and activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway. PMID:20333648 EV71-induced COX-2 expression associated with PGE(2) production is mediated through activation of c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK to initiate the expression of AP-1. |
| GO:0010628 positive regulation of gene expression | IMP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: Src signalling increases expression of target genes (c-fos, MMP-9, COX-2) in rat cells. Reason: Supported indirect downstream outcome of the kinase; non-core. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:19763735 LTA induced MMP-9 expression and activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway. PMID:20333648 EV71-induced COX-2 expression associated with PGE(2) production is mediated through activation of c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK to initiate the expression of AP-1. |
| GO:0010628 positive regulation of gene expression | IMP PMID:19763735 Lipoteichoic acid induces matrix metalloproteinase-9 express... | KEEP AS NON CORE | Summary: Src signalling increases expression of target genes (c-fos, MMP-9, COX-2) in rat cells. Reason: Supported indirect downstream outcome of the kinase; non-core. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:19763735 LTA induced MMP-9 expression and activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway. PMID:20333648 EV71-induced COX-2 expression associated with PGE(2) production is mediated through activation of c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK to initiate the expression of AP-1. |
| GO:0010628 positive regulation of gene expression | IMP PMID:20333648 EV71 induces COX-2 expression via c-Src/PDGFR/PI3K/Akt/p42/p... | KEEP AS NON CORE | Summary: Src signalling increases expression of target genes (c-fos, MMP-9, COX-2) in rat cells. Reason: Supported indirect downstream outcome of the kinase; non-core. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:19763735 LTA induced MMP-9 expression and activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway. PMID:20333648 EV71-induced COX-2 expression associated with PGE(2) production is mediated through activation of c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK to initiate the expression of AP-1. |
| GO:0010629 negative regulation of gene expression | IMP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: IMP: c-Src inhibition raises p27(Kip1) levels in mesangial cells. Reason: Indirect downstream effect of PDGF-Src signalling; non-core. Supporting Evidence: PMID:16530387 Furthermore, inhibition of c-Src increased p27(Kip1) cyclin kinase inhibitor, and attenuated PDGF-induced pRb phosphorylation and CDK2 activity. |
| GO:0010632 regulation of epithelial cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: regulation of epithelial cell migration. Reason: Src regulates migration through focal adhesion turnover. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0010634 positive regulation of epithelial cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: positive regulation of epithelial cell migration. Reason: Src promotes migration through focal adhesion turnover. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0010907 positive regulation of glucose metabolic process | IMP PMID:19230846 Synergistic activation of glucose-6-phosphate dehydrogenase ... | KEEP AS NON CORE | Summary: IMP: Src inhibitors decrease G6PD activity in obese Zucker rat liver. Reason: Pharmacological evidence (inhibitors not specific for Src itself); a context-specific metabolic outcome. Non-core. Supporting Evidence: PMID:19230846 Inhibition of PI3 kinase and Src kinases decreased (p < 0.05) G6PD activity in the fa/fa but not in the lean rat liver, suggesting that G6PD activity is regulated by PI3/Src kinase signaling pathways. file:rat/Src/Src-deep-research-manual.md Most rat papers use pharmacological inhibitors (PP1, PP2, herbimycin A) or antibodies that do not distinguish Src from other Src-family kinases |
| GO:0010954 positive regulation of protein processing | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of protein processing. Reason: Peripheral downstream effect. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0014856 skeletal muscle cell proliferation | IEP PMID:2447874 Proto-oncogene expression in proliferating and differentiati... | MARK AS OVER ANNOTATED | Summary: IEP: c-src transcripts detected only in proliferating, not differentiated, L6 skeletal muscle cells. Reason: Expression correlation only; no evidence that Src performs a step of skeletal muscle cell proliferation. Supporting Evidence: PMID:2447874 c-myb, c-fos, c-src and c-fms transcripts were observed only in proliferating cells. |
| GO:0014911 positive regulation of smooth muscle cell migration | IMP PMID:19736311 Src-dependent STAT-3-mediated expression of monocyte chemoat... | KEEP AS NON CORE | Summary: IMP: 15(S)-HETE-induced rat VSMC migration depends on Src-STAT-3 signalling. Reason: Supported context-specific downstream role. Non-core. Supporting Evidence: PMID:19736311 15(S)-HETE-induced VSMC migration was dependent on Src-mediated activation of signal transducer and activator of transcription-3 (STAT-3). |
| GO:0016004 phospholipase activator activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: ISO from human SRC (IDA, PMID:11606584): phospholipase activator activity. Reason: Src stimulates phospholipases (PLC-gamma, PLD) by phosphorylating them or their regulators, an outcome of its kinase activity. The activator MF implies a non-catalytic activating role and conflates downstream effect with the enzyme activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P12931 · human SRC SUPPORTS SOURCE BUT NOT TARGET Donor carries this term with experimental support; the concern is the scope of the term for a signalling kinase, not the donor evidence. Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. |
| GO:0016020 membrane | IDA PMID:10698670 Rat testicular Src: normal distribution and involvement in e... | MODIFY | Summary: Generic membrane. Reason: Correct but less specific than the evidence: Src is myristoyl-anchored at the plasma membrane. Replace with GO:0005886 plasma membrane (descendant of membrane, already accepted for this gene). Proposed replacements: plasma membrane Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. |
| GO:0016020 membrane | ISO GO_REF:0000121 | MODIFY | Summary: Generic membrane. Reason: Correct but less specific than the evidence: Src is myristoyl-anchored at the plasma membrane. Replace with GO:0005886 plasma membrane (descendant of membrane, already accepted for this gene). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98397 · mouse Src SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: plasma membrane Supporting Evidence: UniProtKB:Q9WUD9 Cell membrane {ECO:0000250|UniProtKB:P05480}; Lipid-anchor UniProtKB:Q9WUD9 Myristoylated at Gly-2, and this is essential for targeting to membranes. |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Generic kinase activity. Reason: Correct but less specific: Src is a non-membrane spanning protein tyrosine kinase (GO:0004715, a descendant of kinase activity already carried by the gene). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98397 · mouse Src SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. |
| GO:0016301 kinase activity | TAS PMID:12007793 Characterization and location of Src-dependent tyrosine phos... | MODIFY | Summary: Generic kinase activity. Reason: Correct but less specific: Src is a non-membrane spanning protein tyrosine kinase (GO:0004715, a descendant of kinase activity already carried by the gene). Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: UniProtKB:Q9WUD9 Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. |
| GO:0016477 cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: cell migration. Reason: Src regulates migration via focal adhesion turnover. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0019899 enzyme binding | IPI PMID:15069201 Unique domain anchoring of Src to synaptic NMDA receptors vi... | KEEP AS NON CORE | Summary: IPI: the Src unique domain binds ND2 (NADH dehydrogenase subunit 2), which anchors Src to the NMDA receptor complex. Reason: The interaction is functionally important in rat neurons (ND2 acts as an adaptor outside mitochondria); no more specific MF term describes binding to ND2 in this non-enzymatic role. Non-core. Supporting Evidence: PMID:15069201 ND2 acts as an adapter protein anchoring Src to the N-methyl-d-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IPI: the Src unique domain binds ND2 (NADH dehydrogenase subunit 2), which anchors Src to the NMDA receptor complex. Reason: The interaction is functionally important in rat neurons (ND2 acts as an adaptor outside mitochondria); no more specific MF term describes binding to ND2 in this non-enzymatic role. Non-core. Supporting Evidence: PMID:15069201 ND2 acts as an adapter protein anchoring Src to the N-methyl-d-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. |
| GO:0019901 protein kinase binding | IPI PMID:12700184 Fer kinase/FerT and adherens junction dynamics in the testis... | KEEP AS NON CORE | Summary: IPI: Fer kinase co-immunoprecipitates with c-Src in rat testis. Reason: Context-specific partner association. Non-core. Supporting Evidence: PMID:12700184 Studies by immunoprecipitation revealed that Fer kinase associated with N-cadherin, gamma-catenin, p120ctn, c-Src |
| GO:0019904 protein domain specific binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: protein domain specific binding (SH2/SH3-mediated interactions). Reason: Src interacts via SH2 and SH3 domains with many partners. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2 (PubMed:8849729). |
| GO:0020037 heme binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO/ISS from human SRC: heme binding; heme enhances inhibitory Tyr-530 phosphorylation. Reason: Curated UniProt activity-regulation statement supports heme as a regulatory ligand; peripheral to the core kinase function. Supporting Evidence: UniProtKB:Q9WUD9 Inhibitory phosphorylation at Tyr-530 is enhanced by heme. |
| GO:0020037 heme binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISO/ISS from human SRC: heme binding; heme enhances inhibitory Tyr-530 phosphorylation. Reason: Curated UniProt activity-regulation statement supports heme as a regulatory ligand; peripheral to the core kinase function. Supporting Evidence: UniProtKB:Q9WUD9 Inhibitory phosphorylation at Tyr-530 is enhanced by heme. |
| GO:0022407 regulation of cell-cell adhesion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: regulation of cell-cell adhesion. Reason: Src phosphorylates adherens junction substrates. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). |
| GO:0030054 cell junction | ISO GO_REF:0000121 | MODIFY | Summary: Generic cell junction. Reason: Correct but general; Src localizes specifically to focal adhesions (accepted) and cell-cell junctions (kept). Replace with those descendants of cell junction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: focal adhesion cell-cell junction Supporting Evidence: UniProtKB:Q9WUD9 Cell junction {ECO:0000250|UniProtKB:P12931} UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. UniProtKB:Q9WUD9 SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: cell differentiation. Reason: Src family kinases act in signalling that influences differentiation in many lineages (e.g. osteoclasts, neurons); a broad non-core process. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0030331 obsolete nuclear estrogen receptor binding | IPI PMID:14751567 Interaction of estrogen receptor alpha with protein kinase C... | KEEP AS NON CORE | Summary: IPI: ERalpha co-immunoprecipitates c-Src and PKCalpha in rat osteoblastic cells. The GOA label carries an obsolete prefix; OLS and the local GO build list GO:0030331 as a live term. Reason: Supported context-specific interaction in rat osteoblasts relevant to non-genomic estrogen signalling. Non-core. Supporting Evidence: PMID:14751567 ERalpha co-immunoprecipitated c-Src and PKCalpha, mostly in its cleaved form (PKMalpha). |
| GO:0030335 positive regulation of cell migration | IMP PMID:20537760 Periodic mechanical stress enhances rat chondrocyte area exp... | KEEP AS NON CORE | Summary: IMP: Src inhibitor PP2 blocks periodic stress-induced chondrocyte migration. Reason: Supported downstream outcome; non-core. Supporting Evidence: PMID:20537760 Area expansion, migration and phosphorylation of PLCgamma1-Tyr(783) and ERK1/2-Thr(202)/Tyr(204) are inhibited (p<0.05) after pretreatment with Src inhibitor (PP2). |
| GO:0030424 axon | IDA PMID:12655602 Active Src expression is induced after rat peripheral nerve ... | KEEP AS NON CORE | Summary: IDA: active Src in axons of rat sciatic nerve. Reason: Supported; c-Src selectively increased after crush by IP. Non-core neuronal location. Supporting Evidence: PMID:12655602 Immunohistochemistry using clone 28 showed that axonal components are the primary sites of active Src expression in the normal sciatic nerve. PMID:12655602 Among the Src tyrosine kinases, active c-Src selectively increased after crushing according to immunoprecipitation and immunoblotting analyses. |
| GO:0030546 signaling receptor activator activity | IDA PMID:15814199 Suppression of Pyk2 attenuated the increased tyrosine phosph... | MODIFY | Summary: IDA (PMID:15814199): signaling receptor activator activity, from a study of NR2A phosphorylation by Src after ischemia. Reason: The paper shows Src (with Pyk2) phosphorylating NR2A; Src enhances NMDA receptor function by tyrosine phosphorylation, i.e. through its kinase activity, not as a receptor activator in the ligand/agonist sense that GO:0030546 describes. Replace with the kinase activity. Proposed replacements: non-membrane spanning protein tyrosine kinase activity Supporting Evidence: PMID:15814199 The data suggested that Pyk2 may be involved in facilitating NR2A tyrosine phosphorylation by Src kinase after I/R. |
| GO:0030900 forebrain development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: forebrain development. Reason: Developmental phenotype context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0031333 negative regulation of protein-containing complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of protein-containing complex assembly. Reason: Peripheral regulatory effect. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0031648 protein destabilization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: protein destabilization. Reason: Peripheral downstream effect of phosphorylation. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0031667 response to nutrient levels | IEP PMID:20357031 Decrease in dietary K intake stimulates the generation of su... | MARK AS OVER ANNOTATED | Summary: IEP: low-K diet increases c-Src expression in rat kidney. Reason: Expression change only; the paper uses a general PTK inhibitor (herbimycin A) and does not establish a Src-specific role in a nutrient response. Supporting Evidence: PMID:20357031 Moreover, LK intake augments the phosphorylation of p38 and ERK MAPK, the expression of c-Src and tyrosine phosphorylation of ROMK channels. |
| GO:0032205 negative regulation of telomere maintenance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of telomere maintenance (acts upstream). Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0032587 ruffle membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: ruffle membrane. Reason: Active Src localizes to membrane ruffles (also seen for v-Src in rat fibroblasts). Non-core. Supporting Evidence: PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0032869 cellular response to insulin stimulus | IEP PMID:19952103 The regulatory domain of protein kinase C delta positively r... | KEEP AS NON CORE | Summary: IEP: insulin stimulates Src activity and its association with IR and PKCdelta in rat skeletal muscle cells. Reason: Supported by rat data including inhibitor effects on glucose uptake; a context-specific signalling role. Supporting Evidence: PMID:15337529 Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta. PMID:15337529 Finally, inhibition of Src decreased insulin-induced glucose uptake. |
| GO:0033146 regulation of intracellular estrogen receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: regulation of intracellular estrogen receptor signalling. Reason: Src participates in non-genomic estrogen signalling. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0033198 response to ATP | IEP PMID:21063895 Functional impact of PTP1B-mediated Src regulation on oxidat... | MARK AS OVER ANNOTATED | Summary: IEP: ATP added to isolated rat brain mitochondria stimulates Src autophosphorylation. Reason: ATP is the co-substrate of the kinase reaction; its addition to isolated mitochondria drives autophosphorylation in vitro. That is a property of the kinase activity, not a cellular response to ATP as a signal. Supporting Evidence: PMID:21063895 Results showed that Src was stimulated by in vitro addition of ATP to mitochondria PMID:18583343 ATP addition induced Src autophosphorylation at Tyr-416 in its catalytic site, leading to its activation, whereas the regulatory Tyr-527 site remained unphosphorylated. |
| GO:0034139 regulation of toll-like receptor 3 signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: regulation of TLR3 signalling. Reason: Peripheral innate-immunity context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0034332 adherens junction organization | IEP PMID:15389520 Protein kinases and adherens junction dynamics in the semini... | KEEP AS NON CORE | Summary: IEP: c-Src is associated with the N-cadherin/beta-catenin complex in rat testis and is induced during Sertoli-germ cell junction assembly. Reason: Correlative, but the paper also reports in vivo c-Src inhibitor effects on germ cell adhesion; non-core. Supporting Evidence: PMID:15389520 Studies using immunoprecipitation have illustrated that these kinases were structurally associated with the N-cadherin/beta-catenin, but not the nectin/afadin, protein complex |
| GO:0034446 substrate adhesion-dependent cell spreading | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: substrate adhesion-dependent cell spreading. Reason: Integrin-dependent spreading requires Src. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0034614 cellular response to reactive oxygen species | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to reactive oxygen species (ISO/ISS); Src phosphorylates PKP3 in response to ROS. Reason: Supported by rat H2O2 studies (PMID:12226102, PMID:8807585); non-core. Supporting Evidence: PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0034614 cellular response to reactive oxygen species | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to reactive oxygen species (ISO/ISS); Src phosphorylates PKP3 in response to ROS. Reason: Supported by rat H2O2 studies (PMID:12226102, PMID:8807585); non-core. Supporting Evidence: PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0034614 cellular response to reactive oxygen species | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular response to reactive oxygen species (ISO/ISS); Src phosphorylates PKP3 in response to ROS. Reason: Supported by rat H2O2 studies (PMID:12226102, PMID:8807585); non-core. Supporting Evidence: PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0035022 positive regulation of Rac protein signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of Rac signal transduction. Reason: Src mediates laminin-induced RAC1 activation. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin |
| GO:0035255 ionotropic glutamate receptor binding | IPI PMID:15814199 Suppression of Pyk2 attenuated the increased tyrosine phosph... | KEEP AS NON CORE | Summary: IPI: Src interacts with NR2A in rat hippocampus after ischemia. Reason: Src binding to the NMDA receptor complex is well documented in rat (also PMID:9005855) and underlies its regulation of the receptor; kept as non-core binding, with the regulatory role captured by GO:2000310. Supporting Evidence: PMID:15814199 I/R led to increases of tyrosine phosphorylation of NR2A and interaction of Pyk2 and Src kinase with NR2A after 6 h of reperfusion. PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. |
| GO:0035306 positive regulation of dephosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: positive regulation of dephosphorylation. Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0035331 negative regulation of hippo signaling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of hippo signalling. Reason: Src activates YAP1 downstream of IL6. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Src is an intracellular signal transducer downstream of many receptor classes. Reason: Correct and central; Src relays signals from receptors to downstream kinases and adaptors. Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Src is an intracellular signal transducer downstream of many receptor classes. Reason: Correct and central; Src relays signals from receptors to downstream kinases and adaptors. Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Src is an intracellular signal transducer downstream of many receptor classes. Reason: Correct and central; Src relays signals from receptors to downstream kinases and adaptors. Supporting Evidence: UniProtKB:Q9WUD9 Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0036035 osteoclast development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: osteoclast development. Reason: Src-null mice are osteopetrotic because osteoclasts fail to resorb bone. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Src acts downstream of PDGF receptors (rat mesangial and endothelial cells). Reason: Supported signalling context; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors PMID:16530387 These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IEP PMID:11417999 pp60(c-src) modulates microvascular endothelial phenotype an... | KEEP AS NON CORE | Summary: Src acts downstream of PDGF receptors (rat mesangial and endothelial cells). Reason: Supported signalling context; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors PMID:16530387 These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src acts downstream of PDGF receptors (rat mesangial and endothelial cells). Reason: Supported signalling context; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors PMID:16530387 These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. |
| GO:0038083 peptidyl-tyrosine autophosphorylation | IMP PMID:18583343 Localization of PTP-1B, SHP-2, and Src exclusively in rat br... | ACCEPT | Summary: IMP: ATP induces Src autophosphorylation at the activation-loop tyrosine in rat brain mitochondria, blocked by PP1/PP2. Reason: Autophosphorylation of the activation-loop tyrosine (Tyr419 in rat numbering, Tyr416 in chicken numbering) is the activating step of Src kinase and is intrinsic to its catalytic function. Supporting Evidence: PMID:18583343 ATP addition induced Src autophosphorylation at Tyr-416 in its catalytic site, leading to its activation, whereas the regulatory Tyr-527 site remained unphosphorylated. UniProtKB:Q9WUD9 Phosphorylation at Tyr-419 increases kinase activity. |
| GO:0038166 angiotensin-activated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Src is activated by angiotensin II via the AT1 receptor and links it to Ras in rat VSMC. Reason: Strong rat evidence (PMID:7586216, PMID:8626602); angiotensin II signalling through Src is one of the best-characterized rat Src pathways and is represented as a core function. Supporting Evidence: PMID:7586216 These data are the first to show that pp60c-src is activated by Ang II. PMID:8626602 These data strongly suggest that a G protein-coupled receptor such as the AT1 receptor can activate the Ras protein cascade via the tyrosine kinase pp60c-src. |
| GO:0042169 SH2 domain binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: SH2 domain binding. Reason: Src SH3/kinase regions bind SH2-containing partners; context-specific. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Pfam; PF00017; SH2; 1. |
| GO:0042311 vasodilation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: vasodilation (acts upstream). Reason: Physiological context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0042476 odontogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: odontogenesis. Reason: Src-null mice fail to erupt teeth due to osteoclast defect. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. |
| GO:0042542 response to hydrogen peroxide | IEP PMID:12226102 Ligand-independent trans-activation of the platelet-derived ... | KEEP AS NON CORE | Summary: IEP: H2O2-induced PDGFR-beta transactivation in rat VSMC requires c-Src. Reason: Supported context-specific role; non-core. Supporting Evidence: PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0043025 neuronal cell body | IDA PMID:2462872 Localization of pp60c-src in growth cone of PC12 cell. | KEEP AS NON CORE | Summary: IDA: pp60c-src immunostaining in the neuronal soma of NGF-treated PC12 cells. Reason: Supported; non-core. Supporting Evidence: PMID:2462872 Immunostaining of pp60c-src is detected in the neuronal soma and the tips of neurites (growth cones). |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:15322113 Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kina... | KEEP AS NON CORE | Summary: Src mediates pro-apoptotic signalling in specific rat contexts (cardiomyocytes, germ cells). Reason: Context-specific outcome; non-core. Supporting Evidence: PMID:15322113 DNA laddering was decreased by mutation of the Tyr(402) Src-binding site in RAFTK, suggesting a central role for Src activity in apoptotic cell death that was confirmed by adenoviral-mediated Src expression. PMID:10698670 spermatocyte degeneration was significantly prevented by cotreatment with 0.1 microM geldanamycin, 10 microM herbimycin A, or 10 microM PP2, which are inhibitors of Src activity. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:10698670 Rat testicular Src: normal distribution and involvement in e... | KEEP AS NON CORE | Summary: Src mediates pro-apoptotic signalling in specific rat contexts (cardiomyocytes, germ cells). Reason: Context-specific outcome; non-core. Supporting Evidence: PMID:15322113 DNA laddering was decreased by mutation of the Tyr(402) Src-binding site in RAFTK, suggesting a central role for Src activity in apoptotic cell death that was confirmed by adenoviral-mediated Src expression. PMID:10698670 spermatocyte degeneration was significantly prevented by cotreatment with 0.1 microM geldanamycin, 10 microM herbimycin A, or 10 microM PP2, which are inhibitors of Src activity. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of apoptotic process. Reason: Src promotes survival signalling in many contexts (e.g. PMID:15856020 in rat hepatocytes). The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: PMID:15856020 The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. |
| GO:0043149 stress fiber assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: stress fiber assembly. Reason: Cytoskeletal outcome of Src signalling. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. |
| GO:0043274 phospholipase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: phospholipase binding. Reason: Src binds and phosphorylates PLC-gamma and PLD. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0044294 dendritic growth cone | IDA PMID:2462872 Localization of pp60c-src in growth cone of PC12 cell. | MODIFY | Summary: IDA (PMID:2462872): pp60c-src in growth cones of NGF-differentiated PC12 cells. Reason: PC12 neurites are not dendrites, and the abstract describes growth cones at neurite tips without assigning dendritic identity. Replace with the parent term GO:0030426 growth cone. Proposed replacements: growth cone Supporting Evidence: PMID:2462872 Immunostaining of pp60c-src is detected in the neuronal soma and the tips of neurites (growth cones). |
| GO:0044325 transmembrane transporter binding | IPI PMID:11834728 Regulation of an ERG K+ current by Src tyrosine kinase. | KEEP AS NON CORE | Summary: Src associates with and phosphorylates ion channels (ERG K+ channel in microglia, KCNQ channels, L-type Ca2+ channel). Reason: Supported by rat co-IP and electrophysiology; channels are substrates whose activity Src modulates. Non-core. Supporting Evidence: PMID:11834728 Co-immunoprecipitation identified an association between the channel protein and Src. PMID:15304482 Immunoprecipitation assays showed that Src associates with KCNQ2-5 subunits but phosphorylates only KCNQ3-5. |
| GO:0044325 transmembrane transporter binding | IPI PMID:15304482 Dual phosphorylations underlie modulation of unitary KCNQ K(... | KEEP AS NON CORE | Summary: Src associates with and phosphorylates ion channels (ERG K+ channel in microglia, KCNQ channels, L-type Ca2+ channel). Reason: Supported by rat co-IP and electrophysiology; channels are substrates whose activity Src modulates. Non-core. Supporting Evidence: PMID:11834728 Co-immunoprecipitation identified an association between the channel protein and Src. PMID:15304482 Immunoprecipitation assays showed that Src associates with KCNQ2-5 subunits but phosphorylates only KCNQ3-5. |
| GO:0044325 transmembrane transporter binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Src associates with and phosphorylates ion channels (ERG K+ channel in microglia, KCNQ channels, L-type Ca2+ channel). Reason: Supported by rat co-IP and electrophysiology; channels are substrates whose activity Src modulates. Non-core. Supporting Evidence: PMID:11834728 Co-immunoprecipitation identified an association between the channel protein and Src. PMID:15304482 Immunoprecipitation assays showed that Src associates with KCNQ2-5 subunits but phosphorylates only KCNQ3-5. |
| GO:0044877 protein-containing complex binding | IPI PMID:12618293 Tyrosine kinase and tyrosine phosphatase participate in regu... | KEEP AS NON CORE | Summary: IPI: Src is part of the NR2A-PSD-95-Src signalling module in rat hippocampus. Reason: Supported association; non-core. Supporting Evidence: PMID:12618293 PTK and PTP were involved in regulating tyrosine phosphorylation of NR2A through changing the interaction among NR2A, PSD-95, Fyn/Src. PMID:20197063 overexpression of PDZ1 domain not only decreased the assembly of NR2A-PSD-95-Src signaling module and the auto-phosphorylation of Src, which mediates NMDA receptor phosphorylation |
| GO:0044877 protein-containing complex binding | IPI PMID:20197063 Transduced PDZ1 domain of PSD-95 decreases Src phosphorylati... | KEEP AS NON CORE | Summary: IPI: Src is part of the NR2A-PSD-95-Src signalling module in rat hippocampus. Reason: Supported association; non-core. Supporting Evidence: PMID:12618293 PTK and PTP were involved in regulating tyrosine phosphorylation of NR2A through changing the interaction among NR2A, PSD-95, Fyn/Src. PMID:20197063 overexpression of PDZ1 domain not only decreased the assembly of NR2A-PSD-95-Src signaling module and the auto-phosphorylation of Src, which mediates NMDA receptor phosphorylation |
| GO:0045056 transcytosis | IDA PMID:15007081 Role of Src-induced dynamin-2 phosphorylation in caveolae-me... | KEEP AS NON CORE | Summary: IDA: Src phosphorylation of dynamin-2 is required for caveolae scission and albumin transcytosis in endothelial cells. Reason: Src phosphorylates dynamin-2, a regulatory step for caveolae release; a real but context-specific role. Supporting Evidence: PMID:15007081 Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial transport of albumin. |
| GO:0045453 bone resorption | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Bone resorption (ISO/ISS): Src is required for osteoclastic bone resorption. Reason: Well established in mice; non-core relative to the kinase activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. |
| GO:0045453 bone resorption | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Bone resorption (ISO/ISS): Src is required for osteoclastic bone resorption. Reason: Well established in mice; non-core relative to the kinase activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. |
| GO:0045453 bone resorption | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bone resorption (ISO/ISS): Src is required for osteoclastic bone resorption. Reason: Well established in mice; non-core relative to the kinase activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. |
| GO:0045747 positive regulation of Notch signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: positive regulation of Notch signalling (via YAP1). Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0045747 positive regulation of Notch signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: positive regulation of Notch signalling (via YAP1). Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0045780 positive regulation of bone resorption | IMP PMID:8514886 Herbimycin A, a pp60c-src tyrosine kinase inhibitor, inhibit... | KEEP AS NON CORE | Summary: IMP: the Src inhibitor herbimycin A inhibits PTH-stimulated bone resorption in fetal rat long bone cultures. Reason: Pharmacological evidence consistent with the Src-null osteopetrosis phenotype; non-core. Supporting Evidence: PMID:8514886 We found that herbimycin A in concentrations of 1-100 ng/ml inhibited bone resorption in each of these systems. |
| GO:0045785 positive regulation of cell adhesion | IDA PMID:15735685 The rat tyrosine phosphatase eta increases cell adhesion by ... | KEEP AS NON CORE | Summary: IDA: r-PTPeta increases rat thyroid cell adhesion by activating c-Src. Reason: Supported; non-core. Supporting Evidence: PMID:15735685 indicating that r-PTPeta regulates cell-substratum adhesion by activating c-Src. |
| GO:0045793 positive regulation of cell size | IMP PMID:20537760 Periodic mechanical stress enhances rat chondrocyte area exp... | KEEP AS NON CORE | Summary: IMP: PP2 inhibits stress-induced chondrocyte area expansion. Reason: Supported pharmacologically; non-core. Supporting Evidence: PMID:20537760 Area expansion, migration and phosphorylation of PLCgamma1-Tyr(783) and ERK1/2-Thr(202)/Tyr(204) are inhibited (p<0.05) after pretreatment with Src inhibitor (PP2). |
| GO:0045821 positive regulation of glycolysis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of glycolytic process. Reason: Peripheral metabolic context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0045913 positive regulation of carbohydrate metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: positive regulation of carbohydrate metabolic process. Reason: Consistent with rat G6PD data (PMID:19230846); peripheral. Supporting Evidence: PMID:19230846 Inhibition of PI3 kinase and Src kinases decreased (p < 0.05) G6PD activity in the fa/fa but not in the lean rat liver, suggesting that G6PD activity is regulated by PI3/Src kinase signaling pathways. |
| GO:0046579 positive regulation of Ras protein signal transduction | IMP PMID:8626602 Angiotensin II controls p21ras activity via pp60c-src. | ACCEPT | Summary: IMP: anti-pp60c-src antibody blocks angiotensin II-stimulated Ras activation in rat VSMC. Reason: Strong rat evidence; Src phosphorylates Ras GAPs (RASA1) and is required for GPCR-induced Ras activation. Represented as a core function. Supporting Evidence: PMID:8626602 Anti-pp60c-src antibody also blocked angiotensin II-stimulated Ras activation and Ras-Raf-1 complex formation. UniProtKB:Q9WUD9 Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IDA PMID:14985360 Involvement of integrins and Src in insulin signaling toward... | KEEP AS NON CORE | Summary: IDA: Src is required for insulin signalling toward autophagic proteolysis in perfused rat liver. Reason: Supported context-specific role. Supporting Evidence: PMID:14985360 Infusion of the integrin-antagonizing hexapeptide GRGDSP or the Src inhibitor PP-2 prevented activation of Src and p38(MAPK) and, consequently, proteolysis inhibition by insulin. |
| GO:0046875 ephrin receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: ephrin receptor binding. Reason: Src binds EPHB1 and other Eph receptors. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. |
| GO:0046875 ephrin receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: ephrin receptor binding. Reason: Src binds EPHB1 and other Eph receptors. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. |
| GO:0048008 platelet-derived growth factor receptor signaling pathway | IEP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: IEP (abstract also includes inhibitor and dominant-negative data): Src relays PDGFR signals to PI3K/Akt and MAPK in rat mesangial cells. Reason: Supported; non-core. Supporting Evidence: PMID:16530387 These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. |
| GO:0048011 neurotrophin TRK receptor signaling pathway | IDA PMID:15546918 PKA phosphorylation of Src mediates Rap1 activation in NGF a... | KEEP AS NON CORE | Summary: IDA: PKA phosphorylation of Src on Ser17 is needed for NGF-induced Rap1 activation in PC12 cells. Reason: Supported context-specific role. Supporting Evidence: PMID:15546918 In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF. |
| GO:0048041 focal adhesion assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: focal adhesion assembly. Reason: Src regulates focal adhesion dynamics. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) |
| GO:0048148 behavioral response to cocaine | IEP PMID:31092585 Synaptic Microtubule-Associated Protein EB3 and SRC Phosphor... | KEEP AS NON CORE | Summary: IEP: SRC activation in NAc synaptoneurosomes during cocaine withdrawal; blocking SRC via SRCIN1 abolished incubation of craving. Reason: The abstract includes a perturbation showing a requirement; behavioural context, non-core. Supporting Evidence: PMID:31092585 In synaptoneurosomal fractions from the NAc of self-administering male rats, the phosphorylation of SRC at an activating site was induced after 1 d of withdrawal PMID:31092585 Blocking SRC phosphorylation during early withdrawal by virally overexpressing SRCIN1, a negative regulator of SRC activity known to interact with EB3, abolished the incubation of cocaine craving in both male and female rats. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (UniProt by similarity); activated Src on perinuclear vesicles in rat fibroblasts. Reason: Supported; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P12931} PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0048471 perinuclear region of cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (UniProt by similarity); activated Src on perinuclear vesicles in rat fibroblasts. Reason: Supported; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P12931} PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0048471 perinuclear region of cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (UniProt by similarity); activated Src on perinuclear vesicles in rat fibroblasts. Reason: Supported; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P12931} PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (UniProt by similarity); activated Src on perinuclear vesicles in rat fibroblasts. Reason: Supported; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P12931} PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:0048477 oogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: oogenesis. Reason: Developmental context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0050839 cell adhesion molecule binding | IPI PMID:19948503 Homophilic adhesion and CEACAM1-S regulate dimerization of C... | KEEP AS NON CORE | Summary: IPI: c-Src binds the cytoplasmic domain of CEACAM1-L, regulated by homophilic adhesion. Reason: Supported; non-core partner binding. Supporting Evidence: PMID:19948503 The balance of SHP-2 and c-Src binding is dependent on the monomer/dimer equilibrium of CEACAM1-L and is regulated by trans-binding UniProtKB:Q9WUD9 Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (PubMed:19948503). |
| GO:0050847 progesterone receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Src mediates non-genomic progesterone receptor signalling in rat aortic SMC. Reason: Supported; non-core. Supporting Evidence: PMID:21440892 The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. |
| GO:0050847 progesterone receptor signaling pathway | IMP PMID:21440892 Extra-nuclear activation of progesterone receptor in regulat... | KEEP AS NON CORE | Summary: Src mediates non-genomic progesterone receptor signalling in rat aortic SMC. Reason: Supported; non-core. Supporting Evidence: PMID:21440892 The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. |
| GO:0051057 positive regulation of small GTPase mediated signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of small GTPase signalling (Ras, Rap1, Rac). Reason: Supported by rat data (PMID:8626602, PMID:15546918); non-core. Supporting Evidence: PMID:8626602 Anti-pp60c-src antibody also blocked angiotensin II-stimulated Ras activation and Ras-Raf-1 complex formation. PMID:15546918 In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF. |
| GO:0051057 positive regulation of small GTPase mediated signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of small GTPase signalling (Ras, Rap1, Rac). Reason: Supported by rat data (PMID:8626602, PMID:15546918); non-core. Supporting Evidence: PMID:8626602 Anti-pp60c-src antibody also blocked angiotensin II-stimulated Ras activation and Ras-Raf-1 complex formation. PMID:15546918 In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF. |
| GO:0051219 phosphoprotein binding | ISO GO_REF:0000121 | MODIFY | Summary: ISO from human SRC: phosphoprotein binding. Reason: Correct but general: the Src SH2 domain binds phosphotyrosine residues (e.g. pTyr402 of Pyk2 in rat PC12 cells). Replace with GO:0001784 phosphotyrosine residue binding, a descendant of phosphoprotein binding. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:8849729 tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. UniProtKB:Q9WUD9 Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2 (PubMed:8849729). |
| GO:0051222 positive regulation of protein transport | IMP PMID:15007081 Role of Src-induced dynamin-2 phosphorylation in caveolae-me... | KEEP AS NON CORE | Summary: IMP: kinase-defective Src prevents caveolar uptake of albumin. Reason: Supported; non-core. Supporting Evidence: PMID:15007081 Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial transport of albumin. |
| GO:0051385 response to mineralocorticoid | IEP PMID:16157790 c-Src-dependent nongenomic signaling responses to aldosteron... | KEEP AS NON CORE | Summary: IEP: aldosterone nongenomic signalling in rat VSMC is mediated through c-Src (blocked by PP2). Reason: Supported context-specific role. Supporting Evidence: PMID:16157790 In conclusion, nongenomic signaling by exogenous aldosterone, mediated through c-Src, is increased in vascular smooth muscle cells from spontaneously hypertensive rats. |
| GO:0051450 myoblast proliferation | IEP PMID:2425941 Differential expression of protooncogenes related to transfo... | MARK AS OVER ANNOTATED | Summary: IEP: c-src transcripts become undetectable when L6 myoblasts differentiate. Reason: Expression correlation only. Supporting Evidence: PMID:2425941 all other c-onc transcripts (c-erbA, c-sis, c-src, c-fes, c-fms, c-fos, c-myc, c-Ki-ras, and the putative tyrosine kinase transcript of the c-fgr gene) become hardly, if at all, detectable. |
| GO:0051602 response to electrical stimulus | IEP PMID:20356829 Learning induces neurotrophin signaling at hippocampal synap... | MARK AS OVER ANNOTATED | Summary: IEP: theta-burst stimulation of hippocampal slices activates Src kinases. Reason: Src activation by an experimental electrical stimulus reflects its activation downstream of NMDA receptors; "response to electrical stimulus" adds no biological information beyond NMDA receptor signalling. Supporting Evidence: PMID:20356829 Theta burst stimulation, which was more effective in this regard than other stimulation patterns, preferentially engaged NMDA receptors that, in turn, activated Src kinases. |
| GO:0051895 negative regulation of focal adhesion assembly | IMP PMID:21440892 Extra-nuclear activation of progesterone receptor in regulat... | KEEP AS NON CORE | Summary: IMP: progesterone inhibits rat aortic SMC migration via Src-dependent RhoA degradation and reduced FAK/paxillin phosphorylation. Reason: Supported; context-specific. Supporting Evidence: PMID:21440892 These findings expend our knowledge of the basis of P4's effect on vascular smooth muscle cell migration |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: Positive regulation of PI3K/Akt signalling. Reason: Supported by rat mesangial cell data; non-core. Supporting Evidence: PMID:16530387 Both PP1 and expression of dominant negative c-Src inhibited PDGF-induced PI 3 kinase, resulting in attenuation of Akt kinase activity. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of PI3K/Akt signalling. Reason: Supported by rat mesangial cell data; non-core. Supporting Evidence: PMID:16530387 Both PP1 and expression of dominant negative c-Src inhibited PDGF-induced PI 3 kinase, resulting in attenuation of Akt kinase activity. |
| GO:0051902 negative regulation of mitochondrial depolarization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of mitochondrial depolarization. Reason: Mitochondrial Src context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase |
| GO:0060065 uterus development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: uterus development. Reason: Developmental context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0060444 branching involved in mammary gland duct morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: mammary branching. Reason: Developmental context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0060491 regulation of cell projection assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: regulation of cell projection assembly. Reason: Cytoskeletal context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. |
| GO:0060576 intestinal epithelial cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: intestinal epithelial cell development. Reason: Developmental context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0060576 intestinal epithelial cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: intestinal epithelial cell development. Reason: Developmental context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0070102 interleukin-6-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: IL-6-mediated signalling. Reason: Src mediates IL6 signalling to YAP1. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0070102 interleukin-6-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: IL-6-mediated signalling. Reason: Src mediates IL6 signalling to YAP1. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration |
| GO:0070161 anchoring junction | IEA GO_REF:0000044 | MODIFY | Summary: Anchoring junction. Reason: Correct but general; Src localizes to focal adhesions, a descendant anchoring junction already accepted for this gene. Replace with GO:0005925 focal adhesion. Proposed replacements: focal adhesion Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. |
| GO:0070161 anchoring junction | ISO GO_REF:0000121 | MODIFY | Summary: Anchoring junction. Reason: Correct but general; Src localizes to focal adhesions, a descendant anchoring junction already accepted for this gene. Replace with GO:0005925 focal adhesion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: focal adhesion Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. |
| GO:0070161 anchoring junction | ISS GO_REF:0000024 | MODIFY | Summary: Anchoring junction. Reason: Correct but general; Src localizes to focal adhesions, a descendant anchoring junction already accepted for this gene. Replace with GO:0005925 focal adhesion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P12931 · human SRC SUPPORTS TRANSFER Donor annotation is sound and the transfer to rat is valid; the issue is granularity, since a more specific term is supported for Src. Proposed replacements: focal adhesion Supporting Evidence: UniProtKB:Q9WUD9 Localizes to focal adhesion sites following integrin engagement. |
| GO:0070301 cellular response to hydrogen peroxide | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular response to H2O2: H2O2 induces c-Src tyrosine phosphorylation in rat mesangial cells and requires c-Src for PDGFR transactivation in VSMC. Reason: Supported; non-core. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0070301 cellular response to hydrogen peroxide | IEP PMID:8807585 Oxidative stress induces tyrosine phosphorylation of PDGF al... | KEEP AS NON CORE | Summary: Cellular response to H2O2: H2O2 induces c-Src tyrosine phosphorylation in rat mesangial cells and requires c-Src for PDGFR transactivation in VSMC. Reason: Supported; non-core. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0070301 cellular response to hydrogen peroxide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to H2O2: H2O2 induces c-Src tyrosine phosphorylation in rat mesangial cells and requires c-Src for PDGFR transactivation in VSMC. Reason: Supported; non-core. Supporting Evidence: PMID:8807585 The tyrosine phosphorylated 60 kDa protein was identified as the cytoplasmic protein tyrosine kinase pp60c-src. PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade. Reason: Src activation is required for ERK activation downstream of GPCRs and RTKs in rat cells; non-core relative to the kinase activity. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:8849729 tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IMP PMID:16530387 c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-ind... | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade. Reason: Src activation is required for ERK activation downstream of GPCRs and RTKs in rat cells; non-core relative to the kinase activity. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:8849729 tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade. Reason: Src activation is required for ERK activation downstream of GPCRs and RTKs in rat cells; non-core relative to the kinase activity. Supporting Evidence: PMID:16530387 Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. PMID:8849729 tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. |
| GO:0070542 response to fatty acid | IEP PMID:19736311 Src-dependent STAT-3-mediated expression of monocyte chemoat... | KEEP AS NON CORE | Summary: IEP: 15(S)-HETE (a fatty acid metabolite) signals through Src-STAT-3 in rat VSMC. Reason: Supported context-specific role. Supporting Evidence: PMID:19736311 15(S)-HETE-induced VSMC migration was dependent on Src-mediated activation of signal transducer and activator of transcription-3 (STAT-3). |
| GO:0070555 response to interleukin-1 | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: response to interleukin-1. Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0070700 BMP receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: BMP receptor binding. Reason: Peripheral partner. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. |
| GO:0071222 cellular response to lipopolysaccharide | IEP PMID:20149623 Butyrate reduced lipopolysaccharide-mediated macrophage migr... | KEEP AS NON CORE | Summary: IEP: LPS induces Src expression and activity, which mediates macrophage migration. Reason: Supported context-specific role. Supporting Evidence: PMID:20149623 These results imply that by virtue of reduction of Src, butyrate could effectively hamper LPS-triggered macrophage locomotion. |
| GO:0071253 connexin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: connexin binding; Src phosphorylates connexin-43. Reason: Supported by curated UniProt. Non-core. Supporting Evidence: UniProtKB:Q9WUD9 Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). |
| GO:0071375 cellular response to peptide hormone stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: cellular response to peptide hormone. Reason: Supported by rat angiotensin II and gastrin data. Non-core. Supporting Evidence: PMID:7586216 These data are the first to show that pp60c-src is activated by Ang II. PMID:12488346 These results suggest that activation of c-Src kinase likely represents a critical step in mediating proliferative effects of both the precursor and fully processed forms of gastrins on IEC. |
| GO:0071393 cellular response to progesterone stimulus | IMP PMID:21440892 Extra-nuclear activation of progesterone receptor in regulat... | KEEP AS NON CORE | Summary: IMP: Src mediates progesterone effects on rat aortic SMC migration. Reason: Supported; non-core. Supporting Evidence: PMID:21440892 The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. |
| GO:0071398 cellular response to fatty acid | IEP PMID:20149623 Butyrate reduced lipopolysaccharide-mediated macrophage migr... | MARK AS OVER ANNOTATED | Summary: IEP: butyrate suppresses Src expression in LPS-treated macrophages. Reason: Expression change in response to butyrate does not show Src performs part of a response to fatty acid. Supporting Evidence: PMID:20149623 LPS-mediated Src induction was greatly suppressed by butyrate and that could be attributable to reduced level of the src transcript. |
| GO:0071456 cellular response to hypoxia | IEP PMID:20380727 Decay accelerating factor (CD55) protects neuronal cells fro... | MARK AS OVER ANNOTATED | Summary: IEP: Src activity is elevated in rat cortical neurons after NaCN chemical hypoxia. Reason: Correlative activation only; no evidence that Src performs a step of the hypoxia response. Supporting Evidence: PMID:20380727 elevated caspase and Src activity |
| GO:0071498 cellular response to fluid shear stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: cellular response to fluid shear stress. Reason: Mechanotransduction context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: PMID:15731459 PI3-K and Akt were resistant to activation when Src kinases were inhibited pharmacologically or by overexpression of a kinase-dead c-Src mutant. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: cellular response to TGF-beta. Reason: Supported also by rat hepatocyte data (PMID:15856020). Non-core. Supporting Evidence: PMID:15856020 The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. |
| GO:0071803 positive regulation of podosome assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of podosome assembly. Reason: Src is required for podosome formation. Non-core. Supporting Evidence: UniProtKB:Q9WUD9 Required for podosome formation |
| GO:0071897 DNA biosynthetic process | IMP PMID:9227431 G protein-coupled receptors control vascular smooth muscle c... | MODIFY | Summary: IMP (PMID:9227431): anti-Src antibodies abolish GPCR-induced DNA synthesis in rat aortic smooth muscle cells. Reason: Src is a signalling kinase upstream of the mitogenic response; it does not perform DNA biosynthesis. The supported claim is positive regulation of DNA biosynthetic process (GO:2000573). Proposed replacements: positive regulation of DNA biosynthetic process Supporting Evidence: PMID:9227431 Our data indicate that the pp60c-src tyrosine kinase is necessary and specific for vascular smooth muscle cell proliferation and DNA synthesis in response to G protein-coupled receptors but not classic growth factor receptors. |
| GO:0086091 regulation of heart rate by cardiac conduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: regulation of heart rate by cardiac conduction. Reason: Physiological context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of canonical Wnt signalling. Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). |
| GO:0090303 positive regulation of wound healing | IMP PMID:20537760 Periodic mechanical stress enhances rat chondrocyte area exp... | MARK AS OVER ANNOTATED | Summary: IMP (PMID:20537760): PP2 inhibits chondrocyte migration and area expansion under periodic mechanical stress. Reason: The abstract describes in vitro chondrocyte migration and spreading, not tissue wound healing; the supported claim is captured by positive regulation of cell migration (GO:0030335). Wound healing over-interprets an in vitro migration assay. Supporting Evidence: PMID:20537760 These findings suggest that periodic mechanical stress promotes chondrocyte area expansion and migration in part through the Src-PLCgamma1-ERK1/2 signaling pathway. |
| GO:0097060 synaptic membrane | IDA PMID:10884433 Nonreceptor tyrosine protein kinase pp60c-src in spatial lea... | KEEP AS NON CORE | Summary: IDA: c-Src protein and kinase activity in the hippocampal synaptic membrane fraction. Reason: Supported by rat fractionation; non-core relative to the glutamatergic synapse rows. Supporting Evidence: PMID:10884433 Training also triggered an increase in c-src protein tyrosine kinase activity that was correlated with its tyrosine dephosphorylation in the synaptic membrane fraction. |
| GO:0097110 scaffold protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: scaffold protein binding (e.g. PSD-95, AFAP1). Reason: Rat PSD-95 binding is directly supported (PMID:14529711). Non-core. Supporting Evidence: PMID:14529711 PSD-95 GST fusion proteins bind directly to purified recombinant Lyn, Src, and Yes in vitro. |
| GO:0097110 scaffold protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO: scaffold protein binding (e.g. PSD-95, AFAP1). Reason: Rat PSD-95 binding is directly supported (PMID:14529711). Non-core. Supporting Evidence: PMID:14529711 PSD-95 GST fusion proteins bind directly to purified recombinant Lyn, Src, and Yes in vitro. |
| GO:0098609 cell-cell adhesion | IEP PMID:15591141 Regulation of ectoplasmic specialization dynamics in the sem... | MARK AS OVER ANNOTATED | Summary: IEP: c-Src levels and p-FAK/c-Src complex increase during androgen-suppression-induced spermatid loss in rat testis. Reason: Correlative protein-level changes; no evidence here that Src performs a step of cell-cell adhesion. Supporting Evidence: PMID:15591141 the protein levels of beta1-integrin, Tyr-phosphorylated focal adhesion kinase (p-FAK), and c-Src were induced during the T suppression-induced germ cell loss and recovery |
| GO:0098858 actin-based cell projection | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA: actin-based cell projection. Reason: Correct but general; the specific actin-based projection supported for Src is the podosome (GO:0002102, a descendant of actin-based cell projection, already on this gene). Proposed replacements: podosome Supporting Evidence: UniProtKB:Q9WUD9 Required for podosome formation |
| GO:0098978 glutamatergic synapse | EXP PMID:9005855 NMDA channel regulation by channel-associated protein tyrosi... | ACCEPT | Summary: Src is associated with NMDA receptors at excitatory (glutamatergic) synapses and regulates their function; it binds PSD-95. Reason: Core neuronal site of Src function in rat (PMID:9005855, PMID:14529711, PMID:15069201). Supporting Evidence: PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. PMID:14529711 Lyn and Yes, as well as Src, but not Lck physically associate with the prominent PSD scaffolding protein PSD-95 in co-immunoprecipitation experiments. |
| GO:0098978 glutamatergic synapse | IDA PMID:14529711 Interactions between Src family protein tyrosine kinases and... | ACCEPT | Summary: Src is associated with NMDA receptors at excitatory (glutamatergic) synapses and regulates their function; it binds PSD-95. Reason: Core neuronal site of Src function in rat (PMID:9005855, PMID:14529711, PMID:15069201). Supporting Evidence: PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. PMID:14529711 Lyn and Yes, as well as Src, but not Lck physically associate with the prominent PSD scaffolding protein PSD-95 in co-immunoprecipitation experiments. |
| GO:0098978 glutamatergic synapse | IDA PMID:9005855 NMDA channel regulation by channel-associated protein tyrosi... | ACCEPT | Summary: Src is associated with NMDA receptors at excitatory (glutamatergic) synapses and regulates their function; it binds PSD-95. Reason: Core neuronal site of Src function in rat (PMID:9005855, PMID:14529711, PMID:15069201). Supporting Evidence: PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. PMID:14529711 Lyn and Yes, as well as Src, but not Lck physically associate with the prominent PSD scaffolding protein PSD-95 in co-immunoprecipitation experiments. |
| GO:0098978 glutamatergic synapse | IEP PMID:14529711 Interactions between Src family protein tyrosine kinases and... | ACCEPT | Summary: Src is associated with NMDA receptors at excitatory (glutamatergic) synapses and regulates their function; it binds PSD-95. This row carries IEP (expression pattern) evidence, which cannot establish a location. Reason: Core neuronal site of Src function in rat (PMID:9005855, PMID:14529711, PMID:15069201). Supporting Evidence: PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. PMID:14529711 Lyn and Yes, as well as Src, but not Lck physically associate with the prominent PSD scaffolding protein PSD-95 in co-immunoprecipitation experiments. |
| GO:0098984 neuron to neuron synapse | IDA PMID:31092585 Synaptic Microtubule-Associated Protein EB3 and SRC Phosphor... | KEEP AS NON CORE | Summary: IDA: SRC phosphorylation measured in rat NAc synaptoneurosome fractions. Reason: Supported synaptic location; non-core. Supporting Evidence: PMID:31092585 In synaptoneurosomal fractions from the NAc of self-administering male rats, the phosphorylation of SRC at an activating site was induced after 1 d of withdrawal |
| GO:0099073 mitochondrion-derived vesicle | IDA PMID:10698670 Rat testicular Src: normal distribution and involvement in e... | UNDECIDED | Summary: IDA (PMID:10698670): mitochondrion-derived vesicle, from a study of Src distribution in rat testis. Reason: The cached abstract reports Src in Sertoli cell cytoplasm, Sertoli/germ cell junctions and dying spermatocytes by immunostaining and electron microscopy and says nothing about mitochondrion-derived vesicles. The full text was not available, so the basis for this term cannot be verified; flagged for checking. Supporting Evidence: PMID:10698670 In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. |
| GO:0099091 postsynaptic specialization, intracellular component | IDA PMID:14529711 Interactions between Src family protein tyrosine kinases and... | ACCEPT | Summary: Src is in the postsynaptic specialization of rat brain, bound to PSD-95 and the NMDA receptor complex. Reason: Core neuronal location for Src regulation of NMDA receptors. Supporting Evidence: PMID:14529711 PSD-95 GST fusion proteins bind directly to purified recombinant Lyn, Src, and Yes in vitro. PMID:15069201 ND2 acts as an adapter protein anchoring Src to the N-methyl-d-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. |
| GO:0099091 postsynaptic specialization, intracellular component | IEP PMID:14529711 Interactions between Src family protein tyrosine kinases and... | ACCEPT | Summary: Src is in the postsynaptic specialization of rat brain, bound to PSD-95 and the NMDA receptor complex. This row carries IEP (expression pattern) evidence, which cannot establish a location. Reason: Core neuronal location for Src regulation of NMDA receptors. Supporting Evidence: PMID:14529711 PSD-95 GST fusion proteins bind directly to purified recombinant Lyn, Src, and Yes in vitro. PMID:15069201 ND2 acts as an adapter protein anchoring Src to the N-methyl-d-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. |
| GO:1900182 positive regulation of protein localization to nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of protein localization to nucleus. Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors |
| GO:1902533 positive regulation of intracellular signal transduction | IMP PMID:19713443 FGF-1-induced reactions for biogenesis of apoE-HDL are media... | KEEP AS NON CORE | Summary: IMP: Src knockdown reduces FGF-1-induced MEK/ERK and PI3K/Akt activation in rat astrocytes. Reason: Supported; non-core. Supporting Evidence: PMID:19713443 We conclude that FGF-1 activates Src for activation of MEK/ERK and PI3K/Akt pathways |
| GO:1902564 negative regulation of neutrophil activation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of neutrophil activation. Reason: Immune context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:1902737 dendritic filopodium | IDA PMID:2462872 Localization of pp60c-src in growth cone of PC12 cell. | UNDECIDED | Summary: IDA (PMID:2462872): dendritic filopodium, from immunolocalization of pp60c-src in NGF-treated PC12 cells. Reason: The cached abstract localizes pp60c-src to the neuronal soma and to growth cones at neurite tips at substrate-adhesion sites; it does not mention filopodia, and PC12 neurites have no established dendritic identity. The full text was not available, so this cannot be verified or refuted. Supporting Evidence: PMID:2462872 Immunostaining of pp60c-src is detected in the neuronal soma and the tips of neurites (growth cones). |
| GO:1903829 positive regulation of protein localization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: positive regulation of protein localization. Reason: Consistent with Src roles in endocytosis and receptor internalization; peripheral. Supporting Evidence: UniProtKB:Q9WUD9 Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) |
| GO:1904263 positive regulation of TORC1 signaling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: positive regulation of TORC1 signalling. Reason: Src phosphorylates OTUB1 promoting RPTOR deubiquitination. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Phosphorylates OTUB1, promoting deubiquitination of RPTOR |
| GO:1904385 cellular response to angiotensin | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Angiotensin II activates pp60c-src in rat VSMC. Reason: Supported; covered more mechanistically by the angiotensin signalling rows. Non-core. Supporting Evidence: PMID:7586216 These data are the first to show that pp60c-src is activated by Ang II. |
| GO:1904385 cellular response to angiotensin | IEP PMID:7586216 Angiotensin II activates pp60c-src in vascular smooth muscle... | KEEP AS NON CORE | Summary: Angiotensin II activates pp60c-src in rat VSMC. Reason: Supported; covered more mechanistically by the angiotensin signalling rows. Non-core. Supporting Evidence: PMID:7586216 These data are the first to show that pp60c-src is activated by Ang II. |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IMP PMID:9227431 G protein-coupled receptors control vascular smooth muscle c... | KEEP AS NON CORE | Summary: IMP: anti-Src antibodies abolish GPCR-induced rat VSMC proliferation. Reason: Supported context-specific role. Supporting Evidence: PMID:9227431 Electroporation of anti-pp60c-src antibodies into cells abolished proliferation in response to these G protein-coupled receptor ligands but not in response to platelet-derived growth factor-BB (PDGF-BB). |
| GO:1905587 positive regulation of outer hair cell apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO (from another mammalian Src ortholog record, RGD:8870238): positive regulation of outer hair cell apoptotic process. Reason: Peripheral context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:1990646 cellular response to prolactin | IEP PMID:8584023 Prolactin receptor is associated with c-src kinase in rat li... | KEEP AS NON CORE | Summary: IEP: prolactin induces association of PRL receptor with pp60c-src and stimulates its kinase in rat hepatocytes. Reason: Supported context-specific signalling role. Supporting Evidence: PMID:8584023 Incubation of hepatocytes with PRL induces the association of PRL receptor with pp60c-src and the resultant stimulation of its tyrosine kinase activity. |
| GO:2000179 positive regulation of neural precursor cell proliferation | IMP PMID:32184165 Donepezil promotes neurogenesis via Src signaling pathway in... | KEEP AS NON CORE | Summary: IMP: the Src inhibitor KX-01 abolishes donepezil-enhanced SVZ neurogenesis in rats. Reason: Pharmacological evidence; non-core. Supporting Evidence: PMID:32184165 Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. file:rat/Src/Src-deep-research-manual.md Most rat papers use pharmacological inhibitors (PP1, PP2, herbimycin A) or antibodies that do not distinguish Src from other Src-family kinases |
| GO:2000256 positive regulation of male germ cell proliferation | IMP PMID:18560731 [Proto-oncogene c-src regulates the viability of rat spermat... | KEEP AS NON CORE | Summary: IMP: antisense c-src reduces rat spermatogonial stem cell viability with reduced p-STAT3. Reason: Weak (viability rather than proliferation), but consistent; non-core. Supporting Evidence: PMID:18560731 The results suggest that proto-oncogene c-src regulates the viability of rat spermatogonial stem cells through p-STAT3. |
| GO:2000394 positive regulation of lamellipodium morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: positive regulation of lamellipodium morphogenesis. Reason: Cytoskeletal context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. |
| GO:2000588 positive regulation of platelet-derived growth factor receptor-beta signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from mouse Src: positive regulation of PDGFR-beta signalling. Reason: Supported also by rat data (PMID:12226102). Non-core. Supporting Evidence: PMID:12226102 H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site, involving the requirement of protein kinase C-delta and c-Src |
| GO:2000641 regulation of early endosome to late endosome transport | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: regulation of early to late endosome transport. Reason: Endosomal trafficking context. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: PMID:19193640 In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. |
| GO:2000811 negative regulation of anoikis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: negative regulation of anoikis. Reason: Src supports anchorage-independent survival. The rat transfer is plausible because Src is a 1:1 ortholog with conserved SH3, SH2 and kinase domains, but the term describes one of many contexts in which the kinase acts rather than its defining activity. Supporting Evidence: UniProtKB:Q9WUD9 Involved in anchorage-independent cell growth |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of extrinsic apoptotic signalling (IBA, ISO). Reason: Src family survival signalling; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of extrinsic apoptotic signalling (IBA, ISO). Reason: Src family survival signalling; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of intrinsic apoptotic signalling (IBA, ISO). Reason: Src family survival signalling; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of intrinsic apoptotic signalling (IBA, ISO). Reason: Src family survival signalling; non-core. Supporting Evidence: UniProtKB:Q9WUD9 Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. |
| GO:2001286 regulation of caveolin-mediated endocytosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO from human SRC: regulation of caveolin-mediated endocytosis. Reason: Supported also by rat endothelial data (PMID:15007081). Non-core. Supporting Evidence: PMID:15007081 Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial transport of albumin. |
| GO:2000310 regulation of NMDA receptor activity | IDA PMID:9005855 NMDA channel regulation by channel-associated protein tyrosi... | NEW | Summary: Rat neuron patch-clamp studies show that endogenous, channel-associated Src regulates NMDA channel activity, requiring the Src unique-domain sequence 40-58; ND2 anchors Src to the receptor complex for this regulation. Reason: Src performs the regulatory step itself (tyrosine phosphorylation of NMDA receptor subunits), so it passes the participation test. Comparator check (QuickGO, GO:2000310 exact): the receptor-phosphorylating kinase DAPK1 and the scaffold Dlg4 carry this term, so regulatory kinases of the receptor are within GO convention. The term is not an ancestor or descendant of any other term on this gene. Supporting Evidence: PMID:9005855 the endogenous tyrosine kinase Src was shown to regulate the activity of NMDA channels. PMID:9005855 Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. PMID:15069201 ND2 acts as an adapter protein anchoring Src to the N-methyl-d-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. |
Loading supporting content…
Download this section (compressed HTML)Q: Many rat Src annotations rest on PP1/PP2, herbimycin A or pan-SFK antibodies (for example PMID:20537760, PMID:19230846, PMID:12655602). Which of these effects are specific to Src rather than Fyn or Yes?
Q: GO:0099073 mitochondrion-derived vesicle (IDA, PMID:10698670) and GO:1902737 dendritic filopodium (IDA, PMID:2462872): does the full text of these papers support the assigned locations, or were broader terms (cytoplasm, growth cone) intended?
Q: Do the neuron-specific N1-Src and N2-Src isoforms, which have altered SH3 ligand specificity, take part in NMDA receptor regulation, or is that role specific to C-Src?
Experiment: Isoform-selective knockdown of the N1/N2 microexons in rat cortical neurons followed by quantitative phosphotyrosine proteomics, compared with pan-Src knockdown.
Hypothesis: N1-Src and N2-Src phosphorylate a distinct set of neuronal substrates from C-Src.
Type: phosphoproteomics
Experiment: Use analog-sensitive Src knock-in or isoform-specific siRNA rescue in rat aortic smooth muscle cells to test angiotensin II-induced Ras activation and proliferation.
Hypothesis: Src, not other SFKs, mediates the pharmacologically defined effects in rat vascular smooth muscle.
Type: chemical genetics
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)