Mouse Syk is a non-receptor protein tyrosine kinase whose tandem SH2 domains couple phosphorylated immune-receptor motifs to intracellular signaling. It phosphorylates adaptor and enzyme substrates and supplies docking surfaces for sustained signaling assemblies. Native mouse studies establish roles in B-cell antigen-receptor, Fc-receptor, lectin and integrin signaling, with developmental effects in B cells and selected T-cell stages and contextual functions in myeloid cells, platelets, osteoclasts and adipocytes. It also regulates receptor trafficking and autophagy in a stimulus-dependent manner. Positive OxLDL-induced macrophage autophagy and negative Tau-clearance regulation are distinct contexts, as are opposing cytokine effects in different innate responses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004713 protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: The broad nucleotide-binding inference can be refined to ATP binding, already represented in this review. Reason: The broad nucleotide-binding inference can be refined to ATP binding, already represented in this review. ATP-dependent substrate and autophosphorylation reactions establish the relevant nucleotide rather than implying binding to every nucleotide. Proposed replacements: ATP binding |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding is required for the directly measured Syk protein kinase reaction. Reason: ATP binding is required for the directly measured Syk protein kinase reaction. PMID:8798454 compares substrate phosphorylation and autophosphorylation of native and epitope-tagged Syk/SykB; this is not an independent ATPase annotation. Supporting Evidence: |
| GO:0016301 kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000117 | MODIFY | Summary: Syk has two distinct experimentally supported domain-recognition modes: its SH2 domains bind phosphotyrosine motifs, while its phosphorylated linker binds SH2 domains on PLCgamma and other effectors. Reason: Syk has two distinct experimentally supported domain-recognition modes: its SH2 domains bind phosphotyrosine motifs, while its phosphorylated linker binds SH2 domains on PLCgamma and other effectors. Refine the broad protein-domain-binding claim to both phosphotyrosine residue binding and SH2 domain binding, already represented here, rather than reversing donor and reader domains. Proposed replacements: phosphotyrosine residue binding SH2 domain binding |
| GO:0005515 protein binding | IPI PMID:16410013 Structural basis for the requirement of two phosphotyrosine ... | MODIFY | Summary: PMID:16410013 directly resolves PLCgamma1 C-terminal SH2 recognition of the doubly phosphorylated Syk linker. Reason: PMID:16410013 directly resolves PLCgamma1 C-terminal SH2 recognition of the doubly phosphorylated Syk linker. Refine bare binding to phospholipase binding and SH2 domain binding. Syk supplies the phosphotyrosines; the SH2 domain in this assay belongs to PLCgamma1, not Syk. Proposed replacements: phospholipase binding SH2 domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713566 Nontranscriptional regulation of SYK by the coactivator OCA-... | REMOVE | Summary: PMID:16713566 directly demonstrates cytoplasmic OCA-BβSYK association and regulation of SYK stability during B-cell development. Reason: PMID:16713566 directly demonstrates cytoplasmic OCA-BβSYK association and regulation of SYK stability during B-cell development. Remove the bare protein-binding term as uninformative while preserving that interaction; the cytoplasmic nontranscriptional role does not justify inventing a transcription-factor-binding function for SYK from OCA-Bβs nuclear coactivator name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20133729 STAT3 is a substrate of SYK tyrosine kinase in B-lineage leu... | MODIFY | Summary: The preserved mouse STAT3 partner is a DNA-binding transcription factor. Reason: The preserved mouse STAT3 partner is a DNA-binding transcription factor. PMID:20133729 directly demonstrates SYKβSTAT3 association and phosphorylation in human leukemia cells with complementary DT40 loss/reconstitution. Retain the curatorβs mouse interaction provenance as a conserved substrate-recognition inference, while distinguishing host and construct species; refine bare binding to DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0000045 autophagosome assembly | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Independent full PMID:25946330 resolves native mouse Syk participation in autophagosome formation: myeloid-specific Syk-deficient bone-marrow macrophages lose OxLDL-triggered ROS/MAPK8 signaling, BECN1βBCL2 dissociation and LC3-positive autophagosome formation. Reason: Independent full PMID:25946330 resolves native mouse Syk participation in autophagosome formation: myeloid-specific Syk-deficient bone-marrow macrophages lose OxLDL-triggered ROS/MAPK8 signaling, BECN1βBCL2 dissociation and LC3-positive autophagosome formation. The kinase supplies a regulatory signaling step, not membrane structural material. This native primary evidence supports the claim beyond the older human transfer, whose current donor record no longer exposes the original source. |
| GO:0001784 phosphotyrosine residue binding | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Syk phosphotyrosine recognition is a conserved tandem-SH2 activity supported by receptor recruitment and independent structural donor evidence. Reason: Mouse Syk phosphotyrosine recognition is a conserved tandem-SH2 activity supported by receptor recruitment and independent structural donor evidence. The original phosphopeptide-array study tests human SH2-domain binding to phosphorylated Chlamydia Tarp; its title emphasizes SHC1 but does not exclude SYK from the array. Independent purified ITAM binding and the SYK tandem-SH2 crystal structure directly establish phosphotyrosine recognition. Preserve the bacterial-effector partner without claiming that the SHC1 survival experiments were performed on SYK. The preserved original source is PMID:20624904. |
| GO:0004672 protein kinase activity | ISO GO_REF:0000096 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:3796 SUPPORTS TRANSFER Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0004672 protein kinase activity | ISO GO_REF:0000119 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P43405 SUPPORTS TRANSFER Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse signaling-receptor association is supported by native ITAM-receptor recruitment and conserved donor receptor-binding evidence; the exact human GPVI pair remains assay-limited. Reason: Mouse signaling-receptor association is supported by native ITAM-receptor recruitment and conserved donor receptor-binding evidence; the exact human GPVI pair remains assay-limited. SYK binds signaling receptors or their phosphorylated signaling chains through SH2-mediated recognition, established independently by CD3/ITAM and IL15RA binding. The original GPVI/GP130 platelet paper establishes pathway proximity but its accessible abstract does not resolve the exact GPVIβSYK pair assay. Retain the supported general receptor-binding claim without mislabeling that abstract as an isolated binary GPVI-binding measurement. The preserved original source is PMID:31145836. |
| GO:0005178 integrin binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Retain the mouse integrin-binding inference with native platelet/integrin signaling corroboration and explicit human donor co-immunoprecipitation provenance. Reason: Retain the mouse integrin-binding inference with native platelet/integrin signaling corroboration and explicit human donor co-immunoprecipitation provenance. PMID:12885943 directly reports Syk coprecipitation with CD18 in activated human neutrophils. Retain this integrin association in its adhesion-cycle context; co-immunoprecipitation does not require an isolated binary complex and inhibition has different effects on attachment and migration. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0010507 negative regulation of autophagy | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: PMID:31324720 directly reports increased autophagic Tau clearance after SYK inhibition/knockdown in human SH-SY5Y cells, with chronic inhibitor rescue of defective autophagy in a mouse tauopathy model. Reason: PMID:31324720 directly reports increased autophagic Tau clearance after SYK inhibition/knockdown in human SH-SY5Y cells, with chronic inhibitor rescue of defective autophagy in a mouse tauopathy model. This supports negative autophagy regulation in that context and does not contradict positive OxLDL/macrophage autophagy in PMID:25946330. Retain both signs with their distinct cell/stimulus settings. Supporting Evidence: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC6737214/ |
| GO:0010508 positive regulation of autophagy | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Native mouse macrophage deletion in PMID:25946330 demonstrates Syk-dependent OxLDL-induced autophagy through ROS/MAPK8 and BECN1 release. Reason: Native mouse macrophage deletion in PMID:25946330 demonstrates Syk-dependent OxLDL-induced autophagy through ROS/MAPK8 and BECN1 release. PMID:26429917 separately shows stress-granule recruitment and clearance in human cell lines/reconstituted systems. Retain positive regulation in these contexts, without assuming the same sign as the Tau/mTOR branch or relabeling every transfected construct as native mouse. |
| GO:0016170 interleukin-15 receptor binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The mouse IL15RA-binding attribution is retained as an orthology-based receptor-association inference from the directly assayed human neutrophil pair. Reason: The mouse IL15RA-binding attribution is retained as an orthology-based receptor-association inference from the directly assayed human neutrophil pair. The original human-neutrophil study explicitly reports physical association of SYK with IL15RA and a SYK-dependent increase in phagocytosis. Retain this receptor-binding context; it does not assign IL15 ligand activity to SYK. The preserved original source is PMID:15123770. Supporting Evidence: |
| GO:0016301 kinase activity | ISO GO_REF:0000119 | MODIFY | Summary: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Reason: Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P43405 SUPPORTS TRANSFER Syk is principally a non-receptor protein tyrosine kinase, with a conserved contextual serine-phosphorylating activity supported by purified SYK/Ikaros experiments in PMID:23071339. Refine the broad kinase/transferase claim to both represented activities; do not erase the experimentally reported serine chemistry or treat it as merely downstream activation of another kinase. Proposed replacements: non-membrane spanning protein tyrosine kinase activity protein serine/threonine kinase activity |
| GO:0019904 protein domain specific binding | ISO GO_REF:0000096 | MODIFY | Summary: Syk has two distinct experimentally supported domain-recognition modes: its SH2 domains bind phosphotyrosine motifs, while its phosphorylated linker binds SH2 domains on PLCgamma and other effectors. Reason: Syk has two distinct experimentally supported domain-recognition modes: its SH2 domains bind phosphotyrosine motifs, while its phosphorylated linker binds SH2 domains on PLCgamma and other effectors. Refine the broad protein-domain-binding claim to both phosphotyrosine residue binding and SH2 domain binding, already represented here, rather than reversing donor and reader domains. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:3796 SUPPORTS TRANSFER Syk has two distinct experimentally supported domain-recognition modes: its SH2 domains bind phosphotyrosine motifs, while its phosphorylated linker binds SH2 domains on PLCgamma and other effectors. Refine the broad protein-domain-binding claim to both phosphotyrosine residue binding and SH2 domain binding, already represented here, rather than reversing donor and reader domains. Proposed replacements: phosphotyrosine residue binding SH2 domain binding |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: The rat donor transfer is corroborated by CBL recognition of phosphorylated SYK and the directly determined CBL-TKB/SYK peptide interface in PMID:18273061. Reason: The rat donor transfer is corroborated by CBL recognition of phosphorylated SYK and the directly determined CBL-TKB/SYK peptide interface in PMID:18273061. Retain ubiquitin protein ligase binding as a contextual regulatory interaction without assigning ubiquitin-transfer catalysis to Syk. Supporting Evidence: |
| GO:0031669 cellular response to nutrient levels | ISO GO_REF:0000119 | UNDECIDED | Summary: The older human donor transfer names a cellular nutrient-level response, but the current donor trace does not recover its experimental source. Reason: The older human donor transfer names a cellular nutrient-level response, but the current donor trace does not recover its experimental source. The inspected stress-granule study uses arsenite/MG132, the macrophage study uses oxidized LDL, and the DEPTOR study tests ephrin/mTOR signaling; none alone establishes a specific nutrient-concentration stimulus. Preserve this claim as unresolved rather than turn general metabolic signaling into a verified nutrient assay. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P43405 UNRESOLVED The older human donor transfer names a cellular nutrient-level response, but the current donor trace does not recover its experimental source. The inspected stress-granule study uses arsenite/MG132, the macrophage study uses oxidized LDL, and the DEPTOR study tests ephrin/mTOR signaling; none alone establishes a specific nutrient-concentration stimulus. Preserve this claim as unresolved rather than turn general metabolic signaling into a verified nutrient assay. |
| GO:0038202 TORC1 signaling | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Reason: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Retain conserved mouse TORC1 participation/positive regulation as a contextual inference, supported independently by mouse tauopathy pharmacology in PMID:31324720. This does not settle a negative TORC1 branch in another condition. |
| GO:0043274 phospholipase binding | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse phospholipase binding is independently supported by native platelet GST-SH2 pull-downs in PMID:27609517, with PLCgamma2 binding weaker than PLCgamma1. Reason: Mouse phospholipase binding is independently supported by native platelet GST-SH2 pull-downs in PMID:27609517, with PLCgamma2 binding weaker than PLCgamma1. SYK associates with PLCgamma proteins through phosphorylation-dependent interfaces, directly supported by PLCgamma domain pull-downs and phosphorylation assays. The original microglial paperβs accessible portions do not resolve an isolated SYKβPLCG2 binding assay, but independent platelet experiments support the general phospholipase-binding claim. PLCgamma2 binding is weaker than PLCgamma1 in the tested platelet lysates and is not equated with equal catalytic efficiency. The preserved original source is PMID:14656219. |
| GO:1904262 negative regulation of TORC1 signaling | ISO GO_REF:0000119 | UNDECIDED | Summary: The exact experimental source behind the older human-to-mouse negative-TORC1 transfer is not recovered by the current donor trace. Reason: The exact experimental source behind the older human-to-mouse negative-TORC1 transfer is not recovered by the current donor trace. Direct DEPTOR/ephrin and Tau studies establish a positive mTOR signaling branch, but an opposite sign in another condition is possible. Retain unresolved negative regulation rather than declare it false solely because the better-characterized context has the opposite sign. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P43405 UNRESOLVED The exact experimental source behind the older human-to-mouse negative-TORC1 transfer is not recovered by the current donor trace. Direct DEPTOR/ephrin and Tau studies establish a positive mTOR signaling branch, but an opposite sign in another condition is possible. Retain unresolved negative regulation rather than declare it false solely because the better-characterized context has the opposite sign. |
| GO:0000045 autophagosome assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Independent full PMID:25946330 resolves native mouse Syk participation in autophagosome formation: myeloid-specific Syk-deficient bone-marrow macrophages lose OxLDL-triggered ROS/MAPK8 signaling, BECN1βBCL2 dissociation and LC3-positive autophagosome formation. Reason: Independent full PMID:25946330 resolves native mouse Syk participation in autophagosome formation: myeloid-specific Syk-deficient bone-marrow macrophages lose OxLDL-triggered ROS/MAPK8 signaling, BECN1βBCL2 dissociation and LC3-positive autophagosome formation. The kinase supplies a regulatory signaling step, not membrane structural material. This native primary evidence supports the claim beyond the older human transfer, whose current donor record no longer exposes the original source. |
| GO:0001784 phosphotyrosine residue binding | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse Syk phosphotyrosine recognition is a conserved tandem-SH2 activity supported by receptor recruitment and independent structural donor evidence. Reason: Mouse Syk phosphotyrosine recognition is a conserved tandem-SH2 activity supported by receptor recruitment and independent structural donor evidence. The original phosphopeptide-array study tests human SH2-domain binding to phosphorylated Chlamydia Tarp; its title emphasizes SHC1 but does not exclude SYK from the array. Independent purified ITAM binding and the SYK tandem-SH2 crystal structure directly establish phosphotyrosine recognition. Preserve the bacterial-effector partner without claiming that the SHC1 survival experiments were performed on SYK. The preserved original source is PMID:20624904. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the conserved mouse serine-kinase claim as contextual donor-supported chemistry; the directly mapped substrate in PMID:23071339 is mouse Ikaros, while native-cell knockdown experiments are human. Reason: Retain the conserved mouse serine-kinase claim as contextual donor-supported chemistry; the directly mapped substrate in PMID:23071339 is mouse Ikaros, while native-cell knockdown experiments are human. PMID:23071339 directly tests purified recombinant SYK phosphorylation of Ikaros, with phospho-amino-acid analysis and mass spectrometry, and native human-cell knockdown supports regulation of Ikaros. The mapped mouse Ikaros S358/S361 correspond to human S361/S364; this is genuine serine phosphorylation by SYK, not merely activation of a downstream serine kinase. Retain this contextual chemistry alongside its principal tyrosine kinase function. The preserved original source is PMID:23071339. Supporting Evidence: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3497833/ Phospho amino acid analysis of the SYK-phosphorylated MBP-IK1 band showed S-phosphorylation. |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse signaling-receptor association is supported by native ITAM-receptor recruitment and conserved donor receptor-binding evidence; the exact human GPVI pair remains assay-limited. Reason: Mouse signaling-receptor association is supported by native ITAM-receptor recruitment and conserved donor receptor-binding evidence; the exact human GPVI pair remains assay-limited. SYK binds signaling receptors or their phosphorylated signaling chains through SH2-mediated recognition, established independently by CD3/ITAM and IL15RA binding. The original GPVI/GP130 platelet paper establishes pathway proximity but its accessible abstract does not resolve the exact GPVIβSYK pair assay. Retain the supported general receptor-binding claim without mislabeling that abstract as an isolated binary GPVI-binding measurement. The preserved original source is PMID:31145836. |
| GO:0005178 integrin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse integrin-binding inference with native platelet/integrin signaling corroboration and explicit human donor co-immunoprecipitation provenance. Reason: Retain the mouse integrin-binding inference with native platelet/integrin signaling corroboration and explicit human donor co-immunoprecipitation provenance. PMID:12885943 directly reports Syk coprecipitation with CD18 in activated human neutrophils. Retain this integrin association in its adhesion-cycle context; co-immunoprecipitation does not require an isolated binary complex and inhibition has different effects on attachment and migration. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0006606 protein import into nucleus | IEA GO_REF:0000107 | MODIFY | Summary: For mouse Syk, the human donor experiments support a conserved regulatory effect on Ikaros localization rather than direct cargo transport by Syk. Reason: For mouse Syk, the human donor experiments support a conserved regulatory effect on Ikaros localization rather than direct cargo transport by Syk. SYK phosphorylates Ikaros and thereby promotes its nuclear accumulation; it is not demonstrated to carry Ikaros through the pore as an import receptor. Refine the role to positive regulation of protein import into nucleus, supported by SYK knockdown and Ikaros phosphosite/phosphomimetic mutants. This is a lateral role correction, not a claim that the regulatory term is a descendant of nuclear import. The preserved original source is PMID:23071339. Proposed replacements: positive regulation of protein import into nucleus |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PMID:31324720 directly reports increased autophagic Tau clearance after SYK inhibition/knockdown in human SH-SY5Y cells, with chronic inhibitor rescue of defective autophagy in a mouse tauopathy model. Reason: PMID:31324720 directly reports increased autophagic Tau clearance after SYK inhibition/knockdown in human SH-SY5Y cells, with chronic inhibitor rescue of defective autophagy in a mouse tauopathy model. This supports negative autophagy regulation in that context and does not contradict positive OxLDL/macrophage autophagy in PMID:25946330. Retain both signs with their distinct cell/stimulus settings. Supporting Evidence: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC6737214/ |
| GO:0010508 positive regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse macrophage deletion in PMID:25946330 demonstrates Syk-dependent OxLDL-induced autophagy through ROS/MAPK8 and BECN1 release. Reason: Native mouse macrophage deletion in PMID:25946330 demonstrates Syk-dependent OxLDL-induced autophagy through ROS/MAPK8 and BECN1 release. PMID:26429917 separately shows stress-granule recruitment and clearance in human cell lines/reconstituted systems. Retain positive regulation in these contexts, without assuming the same sign as the Tau/mTOR branch or relabeling every transfected construct as native mouse. |
| GO:0016170 interleukin-15 receptor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse IL15RA-binding attribution is retained as an orthology-based receptor-association inference from the directly assayed human neutrophil pair. Reason: The mouse IL15RA-binding attribution is retained as an orthology-based receptor-association inference from the directly assayed human neutrophil pair. The original human-neutrophil study explicitly reports physical association of SYK with IL15RA and a SYK-dependent increase in phagocytosis. Retain this receptor-binding context; it does not assign IL15 ligand activity to SYK. The preserved original source is PMID:15123770. Supporting Evidence: |
| GO:0031669 cellular response to nutrient levels | IEA GO_REF:0000107 | UNDECIDED | Summary: The older human donor transfer names a cellular nutrient-level response, but the current donor trace does not recover its experimental source. Reason: The older human donor transfer names a cellular nutrient-level response, but the current donor trace does not recover its experimental source. The inspected stress-granule study uses arsenite/MG132, the macrophage study uses oxidized LDL, and the DEPTOR study tests ephrin/mTOR signaling; none alone establishes a specific nutrient-concentration stimulus. Preserve this claim as unresolved rather than turn general metabolic signaling into a verified nutrient assay. |
| GO:0038202 TORC1 signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Reason: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Retain conserved mouse TORC1 participation/positive regulation as a contextual inference, supported independently by mouse tauopathy pharmacology in PMID:31324720. This does not settle a negative TORC1 branch in another condition. |
| GO:0043274 phospholipase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse phospholipase binding is independently supported by native platelet GST-SH2 pull-downs in PMID:27609517, with PLCgamma2 binding weaker than PLCgamma1. Reason: Mouse phospholipase binding is independently supported by native platelet GST-SH2 pull-downs in PMID:27609517, with PLCgamma2 binding weaker than PLCgamma1. SYK associates with PLCgamma proteins through phosphorylation-dependent interfaces, directly supported by PLCgamma domain pull-downs and phosphorylation assays. The original microglial paperβs accessible portions do not resolve an isolated SYKβPLCG2 binding assay, but independent platelet experiments support the general phospholipase-binding claim. PLCgamma2 binding is weaker than PLCgamma1 in the tested platelet lysates and is not equated with equal catalytic efficiency. The preserved original source is PMID:14656219. |
| GO:1904262 negative regulation of TORC1 signaling | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact experimental source behind the older human-to-mouse negative-TORC1 transfer is not recovered by the current donor trace. Reason: The exact experimental source behind the older human-to-mouse negative-TORC1 transfer is not recovered by the current donor trace. Direct DEPTOR/ephrin and Tau studies establish a positive mTOR signaling branch, but an opposite sign in another condition is possible. Retain unresolved negative regulation rather than declare it false solely because the better-characterized context has the opposite sign. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:8629002 Activation of BTK by a phosphorylation mechanism initiated b... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:9199344 Shc contains two Grb2 binding sites needed for efficient for... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004713 protein tyrosine kinase activity | IMP PMID:33782605 Gain-of-function variants in SYK cause immune dysregulation ... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | KEEP AS NON CORE | Summary: Mouse BCR reconstitution in PMID:8626447 restores MAPK activation through catalytically active Syk, and native mast-cell Syk loss in PMID:9000133 disrupts receptor-triggered downstream signaling. Reason: Mouse BCR reconstitution in PMID:8626447 restores MAPK activation through catalytically active Syk, and native mast-cell Syk loss in PMID:9000133 disrupts receptor-triggered downstream signaling. Retain positive MAPK regulation as an established signaling output, with distinct receptor contexts and no claim that SYK is itself MAPK. |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: Mouse BCR reconstitution in PMID:8626447 restores MAPK activation through catalytically active Syk, and native mast-cell Syk loss in PMID:9000133 disrupts receptor-triggered downstream signaling. Reason: Mouse BCR reconstitution in PMID:8626447 restores MAPK activation through catalytically active Syk, and native mast-cell Syk loss in PMID:9000133 disrupts receptor-triggered downstream signaling. Retain positive MAPK regulation as an established signaling output, with distinct receptor contexts and no claim that SYK is itself MAPK. |
| GO:0032752 positive regulation of interleukin-3 production | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19098920 Fc receptor gamma-chain, a constitutive component of the IL-... | MODIFY | Summary: The preserved P20491 partner is the Fc-receptor common gamma signaling chain. Reason: The preserved P20491 partner is the Fc-receptor common gamma signaling chain. PMID:19098920 places its ITAM in an IL3-receptor complex that recruits Syk; independent quantitative Fc-receptor gamma phosphopeptide binding in PMID:8810294 supports phosphotyrosine recognition. Refine bare binding without assigning IL3 ligand recognition to Syk. Proposed replacements: phosphotyrosine residue binding |
| GO:0006606 protein import into nucleus | ISO PMID:23071339 Serine phosphorylation by SYK is critical for nuclear locali... | MODIFY | Summary: For mouse Syk, the human donor experiments support a conserved regulatory effect on Ikaros localization rather than direct cargo transport by Syk. Reason: For mouse Syk, the human donor experiments support a conserved regulatory effect on Ikaros localization rather than direct cargo transport by Syk. SYK phosphorylates Ikaros and thereby promotes its nuclear accumulation; it is not demonstrated to carry Ikaros through the pore as an import receptor. Refine the role to positive regulation of protein import into nucleus, supported by SYK knockdown and Ikaros phosphosite/phosphomimetic mutants. This is a lateral role correction, not a claim that the regulatory term is a descendant of nuclear import. The preserved original source is PMID:23071339. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P43405 SUPPORTS TRANSFER For mouse Syk, the human donor experiments support a conserved regulatory effect on Ikaros localization rather than direct cargo transport by Syk. SYK phosphorylates Ikaros and thereby promotes its nuclear accumulation; it is not demonstrated to carry Ikaros through the pore as an import receptor. Refine the role to positive regulation of protein import into nucleus, supported by SYK knockdown and Ikaros phosphosite/phosphomimetic mutants. This is a lateral role correction, not a claim that the regulatory term is a descendant of nuclear import. The preserved original source is PMID:23071339. Proposed replacements: positive regulation of protein import into nucleus |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:27609517 TULA-2 Protein Phosphatase Suppresses Activation of Syk thro... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0038063 collagen-activated tyrosine kinase receptor signaling pathway | IMP PMID:27609517 TULA-2 Protein Phosphatase Suppresses Activation of Syk thro... | MODIFY | Summary: Live GO:0038063 requires the collagen receptor itself to possess tyrosine kinase activity. Reason: Live GO:0038063 requires the collagen receptor itself to possess tyrosine kinase activity. Full PMID:27609517 instead examines GPVIβFcRgamma signaling in platelets; GPVI recruits the non-receptor kinase Syk and is not a receptor tyrosine kinase. Correct to collagen-activated signaling pathway GO:0038065, preserving the experimentally demonstrated pathway while removing the unsupported receptor-enzyme class. Proposed replacements: collagen-activated signaling pathway Supporting Evidence: |
| GO:0042169 SH2 domain binding | IDA PMID:27609517 TULA-2 Protein Phosphatase Suppresses Activation of Syk thro... | ACCEPT | Summary: Full PMID:27609517 directly pulls down mouse platelet Syk with GST-PLCgamma SH2 domains, with phosphorylation-dependent enrichment. Reason: Full PMID:27609517 directly pulls down mouse platelet Syk with GST-PLCgamma SH2 domains, with phosphorylation-dependent enrichment. Retain SH2 domain binding as written: PLCgamma supplies the recognized SH2 domain. The older replacement with phosphotyrosine residue binding reversed the molecular direction of this assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26195794 Protein tyrosine phosphatase SAP-1 protects against colitis ... | MODIFY | Summary: Full PMID:26195794 identifies c-Src-phosphorylated CEACAM20 binding to Syk and downstream NF-kappaB signaling. Reason: Full PMID:26195794 identifies c-Src-phosphorylated CEACAM20 binding to Syk and downstream NF-kappaB signaling. The preserved Q9D2Z1 partner and curated mouse SH2 recognition support refinement to phosphotyrosine residue binding, without converting the SAP1 phosphatase into Sykβs own activity. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22496641 CEACAM1 negatively regulates IL-1Ξ² production in LPS activat... | MODIFY | Summary: The preserved P25911 partner is mouse Lyn. Reason: The preserved P25911 partner is mouse Lyn. Full PMID:22496641 explicitly reports that immunoprecipitating Lyn pulls down Syk in LPS-treated wild-type neutrophils (Figure S5A). Refine the generic interaction to protein tyrosine kinase binding, retaining its co-immunoprecipitation and stimulus context rather than asserting an isolated binary interface. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:22496641 we IPed Lyn and found that Syk was specifically pulled down in LPS treated WT neutrophils |
| GO:0019902 phosphatase binding | IPI PMID:22496641 CEACAM1 negatively regulates IL-1Ξ² production in LPS activat... | KEEP AS NON CORE | Summary: Full PMID:22496641 directly examines the TLR4βSYKβCEACAM1βSHP1 complex in LPS-treated mouse neutrophils. Reason: Full PMID:22496641 directly examines the TLR4βSYKβCEACAM1βSHP1 complex in LPS-treated mouse neutrophils. Retain the phosphatase/receptor association in this contextual complex, distinguishing SHP1 recruitment through CEACAM1 from direct isolated SYKβSHP1 contact. Supporting Evidence: |
| GO:0035325 Toll-like receptor binding | IPI PMID:22496641 CEACAM1 negatively regulates IL-1Ξ² production in LPS activat... | KEEP AS NON CORE | Summary: Full PMID:22496641 directly examines the TLR4βSYKβCEACAM1βSHP1 complex in LPS-treated mouse neutrophils. Reason: Full PMID:22496641 directly examines the TLR4βSYKβCEACAM1βSHP1 complex in LPS-treated mouse neutrophils. Retain the phosphatase/receptor association in this contextual complex, distinguishing SHP1 recruitment through CEACAM1 from direct isolated SYKβSHP1 contact. Supporting Evidence: |
| GO:0004674 protein serine/threonine kinase activity | ISO PMID:23071339 Serine phosphorylation by SYK is critical for nuclear locali... | KEEP AS NON CORE | Summary: Retain the conserved mouse serine-kinase claim as contextual donor-supported chemistry; the directly mapped substrate in PMID:23071339 is mouse Ikaros, while native-cell knockdown experiments are human. Reason: Retain the conserved mouse serine-kinase claim as contextual donor-supported chemistry; the directly mapped substrate in PMID:23071339 is mouse Ikaros, while native-cell knockdown experiments are human. PMID:23071339 directly tests purified recombinant SYK phosphorylation of Ikaros, with phospho-amino-acid analysis and mass spectrometry, and native human-cell knockdown supports regulation of Ikaros. The mapped mouse Ikaros S358/S361 correspond to human S361/S364; this is genuine serine phosphorylation by SYK, not merely activation of a downstream serine kinase. Retain this contextual chemistry alongside its principal tyrosine kinase function. The preserved original source is PMID:23071339. Supporting Evidence: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3497833/ Phospho amino acid analysis of the SYK-phosphorylated MBP-IK1 band showed S-phosphorylation. |
| GO:0005515 protein binding | IPI PMID:10872802 Molecular cloning of the mouse APS as a member of the Lnk fa... | UNDECIDED | Summary: The preserved mouse APS interaction cites PMID:10872802. Reason: The preserved mouse APS interaction cites PMID:10872802. The accessible abstract demonstrates APS phosphorylation during cytokine/BCR stimulation but does not expose the exact SYKβAPS binding assay. Normal full-text recovery remained unavailable. Retain this source-specific IPI uncertainty rather than assign APSβs adaptor function to Syk or reject the annotation from its title. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | MODIFY | Summary: PMID:8626447 demonstrates recruitment of Syk to the reconstituted BCR in mouse AtT20 cells. Reason: PMID:8626447 demonstrates recruitment of Syk to the reconstituted BCR in mouse AtT20 cells. The preserved CD79A partner provides an ITAM recognized by tandem SH2 domains; quantitative/structural donor studies independently establish this binding mode. Refine bare binding to phosphotyrosine residue binding without describing the nonlymphoid reconstitution as native B-cell physiology. Proposed replacements: phosphotyrosine residue binding |
| GO:0001819 positive regulation of cytokine production | IGI PMID:19770268 A murine DC-SIGN homologue contributes to early host defense... | KEEP AS NON CORE | Summary: Full PMID:19770268 identifies native mouse SIGNR3-dependent antibacterial cytokine signaling through its intracellular tyrosine motif and Syk. Reason: Full PMID:19770268 identifies native mouse SIGNR3-dependent antibacterial cytokine signaling through its intracellular tyrosine motif and Syk. Retain positive cytokine regulation as a defined C-type lectin context, not an invariant sign for all TLR cytokines. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17086186 Integrin signaling in neutrophils and macrophages uses adapt... | MODIFY | Summary: Full PMID:17086186 uses native mouse integrin-triggered cells and Syk/DAP12 mutants to establish the requirement for Syk SH2 recognition of phosphorylated ITAM adaptors DAP12 and FcRgamma. Reason: Full PMID:17086186 uses native mouse integrin-triggered cells and Syk/DAP12 mutants to establish the requirement for Syk SH2 recognition of phosphorylated ITAM adaptors DAP12 and FcRgamma. Refine each preserved bare-binding partner to phosphotyrosine residue binding; no change is made to the original partner payloads. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15845454 Syk-dependent cytokine induction by Dectin-1 reveals a novel... | MODIFY | Summary: PMID:15845454 directly links phosphorylated Dectin1 cytoplasmic tyrosine to Syk recruitment and cytokine signaling. Reason: PMID:15845454 directly links phosphorylated Dectin1 cytoplasmic tyrosine to Syk recruitment and cytokine signaling. Refine the bare binding term to phosphotyrosine residue binding, with the single receptor hemITAM distinguished from tandem-ITAM signaling chains. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:11672534 Inhibition of beta 2 integrin receptor and Syk kinase signal... | MODIFY | Summary: PMID:11672534 directly identifies Fgr SH2 association with Syk Tyr342 and inhibition of Syk/integrin signaling. Reason: PMID:11672534 directly identifies Fgr SH2 association with Syk Tyr342 and inhibition of Syk/integrin signaling. Refine general kinase binding to protein tyrosine kinase binding; Fgrβs SH2 domain recognizes Syk, so this is not a reason to replace the claim with Syk phosphotyrosine recognition. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: |
| GO:0004713 protein tyrosine kinase activity | IMP PMID:16456001 Scaffolding adapter Grb2-associated binder 2 requires Syk to... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0005515 protein binding | IPI PMID:16456001 Scaffolding adapter Grb2-associated binder 2 requires Syk to... | REMOVE | Summary: PMID:16456001 places Syk upstream of Gab2 phosphorylation in Fc-epsilon-receptor signaling, with Grb2-binding sites controlling assembly. Reason: PMID:16456001 places Syk upstream of Gab2 phosphorylation in Fc-epsilon-receptor signaling, with Grb2-binding sites controlling assembly. Preserve that substrate/complex relationship while removing the uninformative bare protein-binding label; a kinase-dependent assembly does not itself specify a new molecular binding term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19124738 RhoH plays critical roles in Fc epsilon RI-dependent signal ... | REMOVE | Summary: PMID:19124738 directly examines native mouse RhoH-dependent Fc-epsilon-receptor signaling and its coupling to Syk. Reason: PMID:19124738 directly examines native mouse RhoH-dependent Fc-epsilon-receptor signaling and its coupling to Syk. Preserve the RhoH interaction provenance but remove bare protein binding as uninformative, without transferring RhoHβs GTPase-family label to Syk. Supporting Evidence: |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:7499277 Selective regulation of Lyn tyrosine kinase by CD45 in immat... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:7499277 Selective regulation of Lyn tyrosine kinase by CD45 in immat... | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0043366 beta selection | IGI PMID:9275205 The Syk and ZAP-70 SH2-containing tyrosine kinases are impli... | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:10872802 Molecular cloning of the mouse APS as a member of the Lnk fa... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:8798454 Differential intrinsic enzymatic activity of Syk and Zap-70 ... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0007166 cell surface receptor signaling pathway | IDA PMID:9099676 Syk activation and dissociation from the B-cell antigen rece... | MODIFY | Summary: Syk transmits several distinct cell-surface receptor pathways, including native Fc-gamma-receptor signaling during phagocytosis. Reason: Refine the general receptor-signaling process to the supported BCR, Fc-epsilon, Fc-gamma phagocytic, stimulatory C-type lectin, integrin and IL-3 branches rather than selecting only BCR. The original receptor experiments remain part of this evidence set; the listed branches are supported independently by the cited studies. Live GO ancestry places GO:0038096 under this existing GO:0007166 assertion, so an additional NEW row would duplicate ancestral coverage. Full PMID:9314552 examines native Syk-deficient mouse macrophages, proximal signaling and receptor-triggered Syk activation; Syk is a signaling participant, not a phagocytic cargo. The paper does not resolve whether catalytic activity or receptor-associated adaptor function accounts for every knockout effect. The IL-3 branch is limited to the basophil signaling context already reviewed, not all IL-3 responses. Proposed replacements: B cell receptor signaling pathway Fc-epsilon receptor signaling pathway Fc-gamma receptor signaling pathway involved in phagocytosis stimulatory C-type lectin receptor signaling pathway integrin-mediated signaling pathway interleukin-3-mediated signaling pathway Supporting Evidence: PMID:9314552 We found that FcΞ³R-mediated Syk activation was impaired in Hckβ/Fgrβ/Lynβ macrophages. This observation provides additional strong evidence for a model of sequential activation of Src family and Syk tyrosine kinases by the FcΞ³Rs. PMID:9314552 Alternatively, the physical association of Syk with phosphorylated receptor tails may allow it to serve an adaptor-type function at cross-linked receptors to allow recruitment of other important proteins to the site of particle binding. |
| GO:0035556 intracellular signal transduction | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:0045579 positive regulation of B cell differentiation | IMP PMID:7477353 Syk tyrosine kinase required for mouse viability and B-cell ... | KEEP AS NON CORE | Summary: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Reason: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Retain positive B-cell differentiation regulation as the developmental consequence of receptor signaling, with sustained SykβSLP65 feedback independently supporting the mechanism. |
| GO:0045588 positive regulation of gamma-delta T cell differentiation | IMP PMID:8790395 Disruption of epithelial gamma delta T cell repertoires by m... | KEEP AS NON CORE | Summary: PMID:8790395 demonstrates selective depletion and developmental arrest of epithelial gamma-delta T-cell subsets in Syk-deficient chimeras, while splenic gamma-delta cells can develop and expand. Reason: PMID:8790395 demonstrates selective depletion and developmental arrest of epithelial gamma-delta T-cell subsets in Syk-deficient chimeras, while splenic gamma-delta cells can develop and expand. Retain the developmental regulation with this tissue/subset distinction rather than universal gamma-delta dependence. |
| GO:0046638 positive regulation of alpha-beta T cell differentiation | IGI PMID:9275205 The Syk and ZAP-70 SH2-containing tyrosine kinases are impli... | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0046641 positive regulation of alpha-beta T cell proliferation | IGI PMID:9275205 The Syk and ZAP-70 SH2-containing tyrosine kinases are impli... | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0050850 positive regulation of calcium-mediated signaling | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | ACCEPT | Summary: Native mouse mast-cell Syk loss and SykβSLP65 complex perturbation establish signal transmission required for receptor-induced calcium responses. Reason: Native mouse mast-cell Syk loss and SykβSLP65 complex perturbation establish signal transmission required for receptor-induced calcium responses. This is positive regulation of calcium signaling through phosphorylation/scaffold organization, not calcium channel or calcium-binding activity of Syk. |
| GO:0001820 serotonin secretion | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:9099676 Syk activation and dissociation from the B-cell antigen rece... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0007166 cell surface receptor signaling pathway | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | MODIFY | Summary: Syk transmits several distinct cell-surface receptor pathways, including native Fc-gamma-receptor signaling during phagocytosis. Reason: Refine the general receptor-signaling process to the supported BCR, Fc-epsilon, Fc-gamma phagocytic, stimulatory C-type lectin, integrin and IL-3 branches rather than selecting only BCR. The original receptor experiments remain part of this evidence set; the listed branches are supported independently by the cited studies. Live GO ancestry places GO:0038096 under this existing GO:0007166 assertion, so an additional NEW row would duplicate ancestral coverage. Full PMID:9314552 examines native Syk-deficient mouse macrophages, proximal signaling and receptor-triggered Syk activation; Syk is a signaling participant, not a phagocytic cargo. The paper does not resolve whether catalytic activity or receptor-associated adaptor function accounts for every knockout effect. The IL-3 branch is limited to the basophil signaling context already reviewed, not all IL-3 responses. Proposed replacements: B cell receptor signaling pathway Fc-epsilon receptor signaling pathway Fc-gamma receptor signaling pathway involved in phagocytosis stimulatory C-type lectin receptor signaling pathway integrin-mediated signaling pathway interleukin-3-mediated signaling pathway Supporting Evidence: PMID:9314552 We found that FcΞ³R-mediated Syk activation was impaired in Hckβ/Fgrβ/Lynβ macrophages. This observation provides additional strong evidence for a model of sequential activation of Src family and Syk tyrosine kinases by the FcΞ³Rs. PMID:9314552 Alternatively, the physical association of Syk with phosphorylated receptor tails may allow it to serve an adaptor-type function at cross-linked receptors to allow recruitment of other important proteins to the site of particle binding. |
| GO:0019370 leukotriene biosynthetic process | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0035556 intracellular signal transduction | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:0043306 positive regulation of mast cell degranulation | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0005524 ATP binding | IDA PMID:8798454 Differential intrinsic enzymatic activity of Syk and Zap-70 ... | ACCEPT | Summary: ATP binding is required for the directly measured Syk protein kinase reaction. Reason: ATP binding is required for the directly measured Syk protein kinase reaction. PMID:8798454 compares substrate phosphorylation and autophosphorylation of native and epitope-tagged Syk/SykB; this is not an independent ATPase annotation. Supporting Evidence: |
| GO:0045579 positive regulation of B cell differentiation | IMP PMID:7477352 Perinatal lethality and blocked B-cell development in mice l... | KEEP AS NON CORE | Summary: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Reason: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Retain positive B-cell differentiation regulation as the developmental consequence of receptor signaling, with sustained SykβSLP65 feedback independently supporting the mechanism. |
| GO:0045588 positive regulation of gamma-delta T cell differentiation | IMP PMID:7477352 Perinatal lethality and blocked B-cell development in mice l... | KEEP AS NON CORE | Summary: PMID:8790395 demonstrates selective depletion and developmental arrest of epithelial gamma-delta T-cell subsets in Syk-deficient chimeras, while splenic gamma-delta cells can develop and expand. Reason: PMID:8790395 demonstrates selective depletion and developmental arrest of epithelial gamma-delta T-cell subsets in Syk-deficient chimeras, while splenic gamma-delta cells can develop and expand. Retain the developmental regulation with this tissue/subset distinction rather than universal gamma-delta dependence. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:7744830 Association of p72syk with the src homology-2 (SH2) domains ... | ACCEPT | Summary: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. Reason: Syk catalyzes protein tyrosine phosphorylation, demonstrated by native mouse immune-cell and recombinant enzyme studies. PMID:8798454 distinguishes the intrinsic catalytic activity of Syk/SykB from ZAP70, PMID:9199344 measures Shc phosphorylation, and PMID:27609517 directly analyzes mouse platelet Syk. Original papers centered on BTK or APS are not rejected from title emphasis because the reaction is independently established. Membrane recruitment is peripheral, not receptor-spanning topology. |
| GO:0007167 enzyme-linked receptor protein signaling pathway | IDA PMID:7744830 Association of p72syk with the src homology-2 (SH2) domains ... | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:11676469 Syk expression and novel function in a wide variety of tissu... | KEEP AS NON CORE | Summary: The older TAS cites an abstract-limited review, but independent full PMID:29235464 directly shows Syk activation and functional involvement downstream of beta-adrenergic stimulation in mouse brown adipocytes. Reason: The older TAS cites an abstract-limited review, but independent full PMID:29235464 directly shows Syk activation and functional involvement downstream of beta-adrenergic stimulation in mouse brown adipocytes. Retain a contextual GPCR signaling role rather than reject it because immunoreceptor signaling is better known. This does not imply all GPCRs require Syk or negate preserved thrombin signaling in Syk-deficient platelets. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Syk is recruited peripherally to phosphorylated membrane-receptor signaling chains, supported by native mouse receptor studies and ITAM/SH2 binding. Reason: Syk is recruited peripherally to phosphorylated membrane-receptor signaling chains, supported by native mouse receptor studies and ITAM/SH2 binding. The PTN002521457 localization assertion is not a claim of integral membrane topology or exclusive membrane residence. |
| GO:0050853 B cell receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0002250 adaptive immune response | IBA GO_REF:0000033 | ACCEPT | Summary: Native mouse Syk loss blocks B-cell developmental/signaling functions and selective T-lineage programs. Reason: Native mouse Syk loss blocks B-cell developmental/signaling functions and selective T-lineage programs. Direct receptor-proximal phosphorylation, rather than phenotype necessity alone, establishes participation in adaptive immunity; chicken descendant evidence is legitimate support for the ancestral inference. |
| GO:0002281 macrophage activation involved in immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Reason: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Retain these native cell-type outputs outside the molecular kinase core; the IBA targetβs own experimental grounding is not circular evidence. Supporting Evidence: |
| GO:0002283 neutrophil activation involved in immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Reason: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Retain these native cell-type outputs outside the molecular kinase core; the IBA targetβs own experimental grounding is not circular evidence. Supporting Evidence: |
| GO:0033630 positive regulation of cell adhesion mediated by integrin | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Full PMID:11940607 shows that Syk-deficient mouse platelets activate Src after adhesion but fail to spread and phosphorylate downstream cytoskeletal substrates. Reason: Full PMID:11940607 shows that Syk-deficient mouse platelets activate Src after adhesion but fail to spread and phosphorylate downstream cytoskeletal substrates. Retain positive integrin-mediated adhesion/spreading regulation; static human neutrophil inhibition assays measure a distinct adhesionβdetachment context. |
| GO:0001525 angiogenesis | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Reason: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Retain vascular morphogenesis/development as contextual organismal functions without asserting cell-autonomous endothelial kinase action or turning hemorrhage alone into every angiogenic mechanism. Supporting Evidence: |
| GO:0002250 adaptive immune response | IEA GO_REF:0000043 | ACCEPT | Summary: Native mouse Syk loss blocks B-cell developmental/signaling functions and selective T-lineage programs. Reason: Native mouse Syk loss blocks B-cell developmental/signaling functions and selective T-lineage programs. Direct receptor-proximal phosphorylation, rather than phenotype necessity alone, establishes participation in adaptive immunity; chicken descendant evidence is legitimate support for the ancestral inference. |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: Syk directly transmits multiple immune receptor signals in mouse. Reason: Syk directly transmits multiple immune receptor signals in mouse. Native Dectin1-dependent cytokine signaling and integrin-dependent antimicrobial responses support innate/immune-system participation beyond B-cell signaling. The broad process remains useful across distinct receptor mechanisms. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:0043306 positive regulation of mast cell degranulation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Reason: PMID:9000133 uses Syk-deficient mouse mast cells and demonstrates defective Fc-epsilon-receptor-triggered mediator production, secretion and degranulation. Retain the specified mast-cell output as contextual biology; the kinase transmits the activation signal and does not catalyze leukotriene synthesis or synthesize serotonin. Pharmacological and genetic response categories are not assumed to require SYK for every alternative agonist. Supporting Evidence: |
| GO:0043366 beta selection | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: Syk directly transmits multiple immune receptor signals in mouse. Reason: Syk directly transmits multiple immune receptor signals in mouse. Native Dectin1-dependent cytokine signaling and integrin-dependent antimicrobial responses support innate/immune-system participation beyond B-cell signaling. The broad process remains useful across distinct receptor mechanisms. |
| GO:0046638 positive regulation of alpha-beta T cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0046641 positive regulation of alpha-beta T cell proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Reason: Full PMID:9275205 shows that combined Syk/Zap70 deficiency blocks pre-TCR-dependent clonal expansion and the double-negative to double-positive transition, whereas single deficiencies do not produce the same block. Retain beta-selection/alpha-beta-lineage regulation as overlapping developmental functions, not a universal unique requirement for Syk at every T-cell stage. Supporting Evidence: |
| GO:0050850 positive regulation of calcium-mediated signaling | IEA GO_REF:0000117 | ACCEPT | Summary: Native mouse mast-cell Syk loss and SykβSLP65 complex perturbation establish signal transmission required for receptor-induced calcium responses. Reason: Native mouse mast-cell Syk loss and SykβSLP65 complex perturbation establish signal transmission required for receptor-induced calcium responses. This is positive regulation of calcium signaling through phosphorylation/scaffold organization, not calcium channel or calcium-binding activity of Syk. |
| GO:0050851 antigen receptor-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Native BCR and Fc-epsilon receptor studies demonstrate Syk-dependent antigen-receptor signal transmission. Reason: Native BCR and Fc-epsilon receptor studies demonstrate Syk-dependent antigen-receptor signal transmission. The broad antigen-receptor term remains valid across both directly supported branches rather than being restricted to B cells. |
| GO:0002752 cell surface pattern recognition receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Native mouse Dectin1 evidence independently supports the cell-surface pattern-recognition receptor signaling claim. Reason: Native mouse Dectin1 evidence independently supports the cell-surface pattern-recognition receptor signaling claim. SYK transmits signals from stimulatory C-type lectin receptors through phosphorylated receptor/adaptor motifs to downstream enzymes. Human dendritic-cell inhibitor experiments in PMID:19358895 and native mouse Dectin-1 studies independently support the catalytic signaling role. The BCR is not its only receptor context. The preserved original source is PMID:19358895. |
| GO:0007159 leukocyte cell-cell adhesion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Reason: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The mouse TNF-signaling transfer is retained as a contextual orthology inference from the human mammary epithelial SYKβTRIP experiment. Reason: The mouse TNF-signaling transfer is retained as a contextual orthology inference from the human mammary epithelial SYKβTRIP experiment. Full PMID:19151749 studies human mammary epithelial cells: SYK binds TRIP, enhances TNF-dependent NF-kappaB activation, and opposes TRIP-associated sensitization to apoptosis. Retain contextual TNF-pathway regulation without making its sign universal across immune and epithelial cells. The preserved original source is PMID:19151749. Supporting Evidence: |
| GO:0030593 neutrophil chemotaxis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Reason: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0031334 positive regulation of protein-containing complex assembly | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Retain mouse regulation of signaling-complex assembly as a conserved Dectin1/caspase8-inflammasome inference; it is distinct from apoptotic execution. Reason: Retain mouse regulation of signaling-complex assembly as a conserved Dectin1/caspase8-inflammasome inference; it is distinct from apoptotic execution. PMID:22267217 explicitly links Dectin-1/SYK signaling to assembly of the CARD9βBCL10βMALT1βcaspase8βASC machinery for IL1B transcription and processing. Retain positive complex-assembly regulation; caspase8 recruitment here does not by itself establish apoptosis. The preserved original source is PMID:22267217. Supporting Evidence: |
| GO:0032733 positive regulation of interleukin-10 production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Native mouse Syk-deficient dendritic cells fail to produce IL10 after Dectin1/yeast stimulation in PMID:15845454, independently grounding the human-to-mouse transfer. Reason: Native mouse Syk-deficient dendritic cells fail to produce IL10 after Dectin1/yeast stimulation in PMID:15845454, independently grounding the human-to-mouse transfer. The opposing LPS/DC result in PMID:26708990 defines stimulus dependence, not an annotation inconsistency. |
| GO:0032735 positive regulation of interleukin-12 production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032755 positive regulation of interleukin-6 production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032757 positive regulation of interleukin-8 production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: The exact donor PMID:25251945 measures human epithelial IL8/CXCL8 secretion. Reason: The exact donor PMID:25251945 measures human epithelial IL8/CXCL8 secretion. Comparative primary PMID:10028286 identifies CXCL8 loss in the mouse/rat lineage, so a conserved upstream Syk kinase does not establish production of that absent endogenous output in native mouse cells. This is a cytokine-repertoire scope error in the transfer, not evidence that mouse Syk lacks inflammatory chemokine signaling or cannot function in a heterologous human system. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P43405 SUPPORTS SOURCE BUT NOT TARGET The exact donor PMID:25251945 measures human epithelial IL8/CXCL8 secretion. Comparative primary PMID:10028286 identifies CXCL8 loss in the mouse/rat lineage, so a conserved upstream Syk kinase does not establish production of that absent endogenous output in native mouse cells. This is a cytokine-repertoire scope error in the transfer, not evidence that mouse Syk lacks inflammatory chemokine signaling or cannot function in a heterologous human system. |
| GO:0032760 positive regulation of tumor necrosis factor production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032930 positive regulation of superoxide anion generation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000119 | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:0043306 positive regulation of mast cell degranulation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Native mouse Fc-epsilon-receptor genetics in PMID:9000133 independently supports the rat-transferred mast-cell/immune-response attribution. Reason: Native mouse Fc-epsilon-receptor genetics in PMID:9000133 independently supports the rat-transferred mast-cell/immune-response attribution. Retain the physiological response as contextual, with kinase signaling rather than mediator synthesis as Sykβs own work. Supporting Evidence: |
| GO:0045579 positive regulation of B cell differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Reason: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Retain positive B-cell differentiation regulation as the developmental consequence of receptor signaling, with sustained SykβSLP65 feedback independently supporting the mechanism. |
| GO:0050776 regulation of immune response | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Native mouse Fc-epsilon-receptor genetics in PMID:9000133 independently supports the rat-transferred mast-cell/immune-response attribution. Reason: Native mouse Fc-epsilon-receptor genetics in PMID:9000133 independently supports the rat-transferred mast-cell/immune-response attribution. Retain the physiological response as contextual, with kinase signaling rather than mediator synthesis as Sykβs own work. Supporting Evidence: |
| GO:0050853 B cell receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0071396 cellular response to lipid | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Retain the mouse cellular lipid-response attribution with direct native mouse OxLDL/Syk evidence from PMID:25946330 in addition to the human microglial donor context. Reason: Retain the mouse cellular lipid-response attribution with direct native mouse OxLDL/Syk evidence from PMID:25946330 in addition to the human microglial donor context. The normally cached publisher page for PMID:32514138 exposes Extended Data Fig4a: endogenous SYK Y525/526 phosphorylation in human iPSC-derived microglia challenged with PC/PS liposomes, with inhibitor controls. This directly supports a lipid-stimulus response despite the PMID cache being abstract-only. It is not proof of direct lipid binding by SYK. The preserved original source is PMID:32514138. Supporting Evidence: url:https://www.nature.com/articles/s41593-020-0650-6 Levels of SYK phosphorylated at Y525/526 in WT iMG stimulated with 70% PC/30% PS liposomes |
| GO:0071639 positive regulation of monocyte chemotactic protein-1 production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The mouse CCL2-production claim is retained as a conserved chemokine-regulatory inference from the human intestinal epithelial donor experiment, not a direct mouse epithelial assay. Reason: The mouse CCL2-production claim is retained as a conserved chemokine-regulatory inference from the human intestinal epithelial donor experiment, not a direct mouse epithelial assay. PMID:25251945 directly studies human intestinal epithelial cells and reports Dectin-1/SYK-dependent beta-glucan-induced IL8 and CCL2 secretion. Retain the specified chemokine output as contextual native human biology, not a newly inferred B-cell core function. The preserved original source is PMID:25251945. Supporting Evidence: |
| GO:0097110 scaffold protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Syk scaffold-protein binding is supported by conserved BLNK/SLP65 recognition and native feedback complexes. Reason: Mouse Syk scaffold-protein binding is supported by conserved BLNK/SLP65 recognition and native feedback complexes. SYK directly engages the BLNK scaffold and phosphorylates it in purified complex assays; sustained SYKβSLP65 association also has an adaptor component. Retain scaffold protein binding without assigning BLNKβs enzymeless scaffold mechanism to SYK as its sole function. The preserved original source is PMID:11606584. |
| GO:0097190 apoptotic signaling pathway | ISO GO_REF:0000119 | UNDECIDED | Summary: The mouse apoptotic-signaling transfer remains unresolved because the traced donor source concerns noncanonical caspase8-dependent IL1beta processing, not a resolved apoptosis assay. Reason: The mouse apoptotic-signaling transfer remains unresolved because the traced donor source concerns noncanonical caspase8-dependent IL1beta processing, not a resolved apoptosis assay. The accessible PMID:22267217 abstract and publisher figure headings establish a noncanonical caspase8 inflammasome for IL1beta processing, not an apoptosis assay. Caspase8 activation alone is not sufficient to infer apoptotic signaling. The complete article remains unavailable after normal PMID and publisher recovery, so retain source-specific uncertainty instead of declaring the experimental annotation false. The preserved original source is PMID:22267217. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P43405 UNRESOLVED The mouse apoptotic-signaling transfer remains unresolved because the traced donor source concerns noncanonical caspase8-dependent IL1beta processing, not a resolved apoptosis assay. The accessible PMID:22267217 abstract and publisher figure headings establish a noncanonical caspase8 inflammasome for IL1beta processing, not an apoptosis assay. Caspase8 activation alone is not sufficient to infer apoptotic signaling. The complete article remains unavailable after normal PMID and publisher recovery, so retain source-specific uncertainty instead of declaring the experimental annotation false. The preserved original source is PMID:22267217. |
| GO:0097242 amyloid-beta clearance | ISO GO_REF:0000119 | UNDECIDED | Summary: The mouse amyloid-clearance transfer remains source-specific uncertainty; TREM2-mediated uptake is not by itself an independently verified Syk assay. Reason: The mouse amyloid-clearance transfer remains source-specific uncertainty; TREM2-mediated uptake is not by itself an independently verified Syk assay. PMID:27477018 directly describes TREM2-dependent uptake of amyloidβlipoprotein complexes, but the accessible abstract does not expose the specific SYK perturbation or construct assay underlying this IDA. Normal recovery and the publisher PDF attempt did not recover full text. Preserve the curatorβs claim as unresolved rather than treating a TREM2-focused abstract as proof that SYK was not tested. The preserved original source is PMID:27477018. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P43405 UNRESOLVED The mouse amyloid-clearance transfer remains source-specific uncertainty; TREM2-mediated uptake is not by itself an independently verified Syk assay. PMID:27477018 directly describes TREM2-dependent uptake of amyloidβlipoprotein complexes, but the accessible abstract does not expose the specific SYK perturbation or construct assay underlying this IDA. Normal recovery and the publisher PDF attempt did not recover full text. Preserve the curatorβs claim as unresolved rather than treating a TREM2-focused abstract as proof that SYK was not tested. The preserved original source is PMID:27477018. Supporting Evidence: |
| GO:1904263 positive regulation of TORC1 signaling | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Reason: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Retain conserved mouse TORC1 participation/positive regulation as a contextual inference, supported independently by mouse tauopathy pharmacology in PMID:31324720. This does not settle a negative TORC1 branch in another condition. |
| GO:1904646 cellular response to amyloid-beta | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The mouse amyloid-response claim is supported by the sourceβs primary microglial/mouse context and amyloid-induced SYK phosphorylation, not merely a human annotation transfer. Reason: The mouse amyloid-response claim is supported by the sourceβs primary microglial/mouse context and amyloid-induced SYK phosphorylation, not merely a human annotation transfer. PMID:29518356 explicitly reports amyloid-enhanced TREM2βDAP12 interaction and downstream SYK phosphorylation. Retain the cellular amyloid-response attribution, distinguishing mouse microglial physiology and receptor/construct assays from a direct human brain experiment. This does not itself establish SYK-mediated amyloid clearance. The preserved original source is PMID:29518356. Supporting Evidence: |
| GO:0002752 cell surface pattern recognition receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Native mouse Dectin1 evidence independently supports the cell-surface pattern-recognition receptor signaling claim. Reason: Native mouse Dectin1 evidence independently supports the cell-surface pattern-recognition receptor signaling claim. SYK transmits signals from stimulatory C-type lectin receptors through phosphorylated receptor/adaptor motifs to downstream enzymes. Human dendritic-cell inhibitor experiments in PMID:19358895 and native mouse Dectin-1 studies independently support the catalytic signaling role. The BCR is not its only receptor context. The preserved original source is PMID:19358895. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse nuclear pool as a contextual orthology inference from SYKβIkaros cellular studies, distinct from the substrateβs own nuclear localization. Reason: Retain the mouse nuclear pool as a contextual orthology inference from SYKβIkaros cellular studies, distinct from the substrateβs own nuclear localization. PMID:23071339 examines SYKβIkaros in human cells and supports a nuclear as well as cytoplasmic pool. Retain contextual nuclear localization rather than exclude it because receptor signaling is mainly cytoplasmic. Nuclear localization of Ikaros is a separate substrate response. The preserved original source is PMID:23071339. |
| GO:0007159 leukocyte cell-cell adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Reason: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse TNF-signaling transfer is retained as a contextual orthology inference from the human mammary epithelial SYKβTRIP experiment. Reason: The mouse TNF-signaling transfer is retained as a contextual orthology inference from the human mammary epithelial SYKβTRIP experiment. Full PMID:19151749 studies human mammary epithelial cells: SYK binds TRIP, enhances TNF-dependent NF-kappaB activation, and opposes TRIP-associated sensitization to apoptosis. Retain contextual TNF-pathway regulation without making its sign universal across immune and epithelial cells. The preserved original source is PMID:19151749. Supporting Evidence: |
| GO:0030593 neutrophil chemotaxis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Reason: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0031334 positive regulation of protein-containing complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse regulation of signaling-complex assembly as a conserved Dectin1/caspase8-inflammasome inference; it is distinct from apoptotic execution. Reason: Retain mouse regulation of signaling-complex assembly as a conserved Dectin1/caspase8-inflammasome inference; it is distinct from apoptotic execution. PMID:22267217 explicitly links Dectin-1/SYK signaling to assembly of the CARD9βBCL10βMALT1βcaspase8βASC machinery for IL1B transcription and processing. Retain positive complex-assembly regulation; caspase8 recruitment here does not by itself establish apoptosis. The preserved original source is PMID:22267217. Supporting Evidence: |
| GO:0032733 positive regulation of interleukin-10 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Syk-deficient dendritic cells fail to produce IL10 after Dectin1/yeast stimulation in PMID:15845454, independently grounding the human-to-mouse transfer. Reason: Native mouse Syk-deficient dendritic cells fail to produce IL10 after Dectin1/yeast stimulation in PMID:15845454, independently grounding the human-to-mouse transfer. The opposing LPS/DC result in PMID:26708990 defines stimulus dependence, not an annotation inconsistency. |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032757 positive regulation of interleukin-8 production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The exact donor PMID:25251945 measures human epithelial IL8/CXCL8 secretion. Reason: The exact donor PMID:25251945 measures human epithelial IL8/CXCL8 secretion. Comparative primary PMID:10028286 identifies CXCL8 loss in the mouse/rat lineage, so a conserved upstream Syk kinase does not establish production of that absent endogenous output in native mouse cells. This is a cytokine-repertoire scope error in the transfer, not evidence that mouse Syk lacks inflammatory chemokine signaling or cannot function in a heterologous human system. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0032930 positive regulation of superoxide anion generation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Reason: Human Dectin1/SYK inhibition in PMID:19358895 directly supports the specified cytokine/oxidase output, and native mouse lectin/integrin studies corroborate receptor-dependent cytokine and ROS signaling. Retain the exact transferred response as contextual; Dectin1-only versus TLR-costimulated conditions differ, and PMID:15845454 specifically preserves yeast-induced IL12 in Syk-null cells. These are not universal requirements across all stimuli. |
| GO:0045579 positive regulation of B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Reason: Native mouse Syk-null hematopoietic studies show a major pro-B/pre-B transition and mature B-cell accumulation defect. Retain positive B-cell differentiation regulation as the developmental consequence of receptor signaling, with sustained SykβSLP65 feedback independently supporting the mechanism. |
| GO:0050853 B cell receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0071396 cellular response to lipid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse cellular lipid-response attribution with direct native mouse OxLDL/Syk evidence from PMID:25946330 in addition to the human microglial donor context. Reason: Retain the mouse cellular lipid-response attribution with direct native mouse OxLDL/Syk evidence from PMID:25946330 in addition to the human microglial donor context. The normally cached publisher page for PMID:32514138 exposes Extended Data Fig4a: endogenous SYK Y525/526 phosphorylation in human iPSC-derived microglia challenged with PC/PS liposomes, with inhibitor controls. This directly supports a lipid-stimulus response despite the PMID cache being abstract-only. It is not proof of direct lipid binding by SYK. The preserved original source is PMID:32514138. Supporting Evidence: url:https://www.nature.com/articles/s41593-020-0650-6 Levels of SYK phosphorylated at Y525/526 in WT iMG stimulated with 70% PC/30% PS liposomes |
| GO:0071639 positive regulation of monocyte chemotactic protein-1 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse CCL2-production claim is retained as a conserved chemokine-regulatory inference from the human intestinal epithelial donor experiment, not a direct mouse epithelial assay. Reason: The mouse CCL2-production claim is retained as a conserved chemokine-regulatory inference from the human intestinal epithelial donor experiment, not a direct mouse epithelial assay. PMID:25251945 directly studies human intestinal epithelial cells and reports Dectin-1/SYK-dependent beta-glucan-induced IL8 and CCL2 secretion. Retain the specified chemokine output as contextual native human biology, not a newly inferred B-cell core function. The preserved original source is PMID:25251945. Supporting Evidence: |
| GO:0097110 scaffold protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse Syk scaffold-protein binding is supported by conserved BLNK/SLP65 recognition and native feedback complexes. Reason: Mouse Syk scaffold-protein binding is supported by conserved BLNK/SLP65 recognition and native feedback complexes. SYK directly engages the BLNK scaffold and phosphorylates it in purified complex assays; sustained SYKβSLP65 association also has an adaptor component. Retain scaffold protein binding without assigning BLNKβs enzymeless scaffold mechanism to SYK as its sole function. The preserved original source is PMID:11606584. |
| GO:0097190 apoptotic signaling pathway | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse apoptotic-signaling transfer remains unresolved because the traced donor source concerns noncanonical caspase8-dependent IL1beta processing, not a resolved apoptosis assay. Reason: The mouse apoptotic-signaling transfer remains unresolved because the traced donor source concerns noncanonical caspase8-dependent IL1beta processing, not a resolved apoptosis assay. The accessible PMID:22267217 abstract and publisher figure headings establish a noncanonical caspase8 inflammasome for IL1beta processing, not an apoptosis assay. Caspase8 activation alone is not sufficient to infer apoptotic signaling. The complete article remains unavailable after normal PMID and publisher recovery, so retain source-specific uncertainty instead of declaring the experimental annotation false. The preserved original source is PMID:22267217. |
| GO:0097242 amyloid-beta clearance | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse amyloid-clearance transfer remains source-specific uncertainty; TREM2-mediated uptake is not by itself an independently verified Syk assay. Reason: The mouse amyloid-clearance transfer remains source-specific uncertainty; TREM2-mediated uptake is not by itself an independently verified Syk assay. PMID:27477018 directly describes TREM2-dependent uptake of amyloidβlipoprotein complexes, but the accessible abstract does not expose the specific SYK perturbation or construct assay underlying this IDA. Normal recovery and the publisher PDF attempt did not recover full text. Preserve the curatorβs claim as unresolved rather than treating a TREM2-focused abstract as proof that SYK was not tested. The preserved original source is PMID:27477018. Supporting Evidence: |
| GO:1904263 positive regulation of TORC1 signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Reason: Full human donor PMID:34634301 demonstrates SYK-dependent DEPTOR Tyr289 phosphorylation and activation of mTORC1/2 in an ephrin-receptor context. Retain conserved mouse TORC1 participation/positive regulation as a contextual inference, supported independently by mouse tauopathy pharmacology in PMID:31324720. This does not settle a negative TORC1 branch in another condition. |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse amyloid-response claim is supported by the sourceβs primary microglial/mouse context and amyloid-induced SYK phosphorylation, not merely a human annotation transfer. Reason: The mouse amyloid-response claim is supported by the sourceβs primary microglial/mouse context and amyloid-induced SYK phosphorylation, not merely a human annotation transfer. PMID:29518356 explicitly reports amyloid-enhanced TREM2βDAP12 interaction and downstream SYK phosphorylation. Retain the cellular amyloid-response attribution, distinguishing mouse microglial physiology and receptor/construct assays from a direct human brain experiment. This does not itself establish SYK-mediated amyloid clearance. The preserved original source is PMID:29518356. Supporting Evidence: |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:9199344 Shc contains two Grb2 binding sites needed for efficient for... | ACCEPT | Summary: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Reason: Syk executes BCR signal transmission by phosphorylating receptor-associated substrates and adaptors. Native mouse enzyme studies, BCR/Syk reconstitution and Shc/BLNK biochemistry independently corroborate the PTN002815343 ancestral inference. Reconstitution in AtT20 cells restores several outputs but is not sufficient for all PLC-dependent responses, as PMID:8626447 explicitly reports. |
| GO:0001775 cell activation | IMP PMID:19136564 Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+... | KEEP AS NON CORE | Summary: Full PMID:19136564 studies Dectin1-stimulated dendritic cells and PLCgamma-dependent activation, including Syk-linked receptor signaling. Reason: Full PMID:19136564 studies Dectin1-stimulated dendritic cells and PLCgamma-dependent activation, including Syk-linked receptor signaling. Retain the cellular activation/lectin response as contextual output, without assigning extracellular lectin recognition to the intracellular kinase. Supporting Evidence: |
| GO:0002223 stimulatory C-type lectin receptor signaling pathway | IMP PMID:19136564 Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+... | ACCEPT | Summary: Native mouse Dectin1 experiments directly link receptor phosphotyrosine-dependent Syk recruitment to downstream signaling and cytokine production. Reason: Native mouse Dectin1 experiments directly link receptor phosphotyrosine-dependent Syk recruitment to downstream signaling and cytokine production. This catalytic receptor-signaling role is established independently of the PLCgamma2-centered title of PMID:19136564. |
| GO:0035556 intracellular signal transduction | IMP PMID:19136564 Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+... | ACCEPT | Summary: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Reason: The broad receptor/intracellular-signaling process remains appropriate for Sykβs experimentally established BCR, Fc-receptor, lectin and integrin contexts. Original mouse BCR reconstitution, mast-cell genetics and lectin-receptor studies supply distinct mechanisms; selecting only BCR as a replacement would discard supported non-BCR signaling. |
| GO:1990858 cellular response to lectin | IMP PMID:19136564 Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+... | KEEP AS NON CORE | Summary: Full PMID:19136564 studies Dectin1-stimulated dendritic cells and PLCgamma-dependent activation, including Syk-linked receptor signaling. Reason: Full PMID:19136564 studies Dectin1-stimulated dendritic cells and PLCgamma-dependent activation, including Syk-linked receptor signaling. Retain the cellular activation/lectin response as contextual output, without assigning extracellular lectin recognition to the intracellular kinase. Supporting Evidence: |
| GO:0018108 peptidyl-tyrosine phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Syk directly catalyzes protein tyrosine phosphorylation, including Gab2-associated Fc-epsilon-receptor signaling and Shc phosphorylation. Reason: Syk directly catalyzes protein tyrosine phosphorylation, including Gab2-associated Fc-epsilon-receptor signaling and Shc phosphorylation. The chicken transfer and mouse substrate study agree on the reaction without making every phosphorylated downstream protein a direct Syk substrate. |
| GO:0120162 positive regulation of cold-induced thermogenesis | IMP PMID:29235464 SYK kinase mediates brown fat differentiation and activation... | KEEP AS NON CORE | Summary: Native mouse adipocyte-specific deletion and beta-agonist experiments directly support contextual Syk-dependent thermogenic regulation. Reason: Native mouse adipocyte-specific deletion and beta-agonist experiments directly support contextual Syk-dependent thermogenic regulation. Full PMID:29235464 uses mouse adipocyte-specific deletion and beta-agonist/inhibitor experiments to establish SYK-dependent brown-fat formation and thermogenic responses. Retain the explicitly comparative human attribution as non-core, not a direct human cold-challenge experiment or universal immune-cell function. The preserved original source is PMID:29235464. Supporting Evidence: |
| GO:0032753 positive regulation of interleukin-4 production | IMP PMID:19098920 Fc receptor gamma-chain, a constitutive component of the IL-... | KEEP AS NON CORE | Summary: PMID:19098920 directly establishes the mouse basophil IL3-receptor/FcRgamma/Syk pathway leading to IL4 production. Reason: PMID:19098920 directly establishes the mouse basophil IL3-receptor/FcRgamma/Syk pathway leading to IL4 production. FcRgamma loss preserves normal development/proliferation but selectively impairs this cytokine branch; do not generalize Syk dependence to every IL3 effect. Supporting Evidence: |
| GO:0038156 interleukin-3-mediated signaling pathway | IMP PMID:19098920 Fc receptor gamma-chain, a constitutive component of the IL-... | KEEP AS NON CORE | Summary: PMID:19098920 directly establishes the mouse basophil IL3-receptor/FcRgamma/Syk pathway leading to IL4 production. Reason: PMID:19098920 directly establishes the mouse basophil IL3-receptor/FcRgamma/Syk pathway leading to IL4 production. FcRgamma loss preserves normal development/proliferation but selectively impairs this cytokine branch; do not generalize Syk dependence to every IL3 effect. Supporting Evidence: |
| GO:0031623 receptor internalization | IDA PMID:23395392 Multimolecular signaling complexes enable Syk-mediated signa... | KEEP AS NON CORE | Summary: Full PMID:23395392 identifies a CD36βintegrinβtetraspaninβFcRgamma assembly that recruits Syk and drives CD36/ligand internalization in macrophages. Reason: Full PMID:23395392 identifies a CD36βintegrinβtetraspaninβFcRgamma assembly that recruits Syk and drives CD36/ligand internalization in macrophages. Retain receptor internalization and LDL-stimulus response with this native signaling context, not direct lipoprotein transport or uptake catalysis by Syk. Supporting Evidence: |
| GO:0071404 cellular response to low-density lipoprotein particle stimulus | IDA PMID:23395392 Multimolecular signaling complexes enable Syk-mediated signa... | KEEP AS NON CORE | Summary: Full PMID:23395392 identifies a CD36βintegrinβtetraspaninβFcRgamma assembly that recruits Syk and drives CD36/ligand internalization in macrophages. Reason: Full PMID:23395392 identifies a CD36βintegrinβtetraspaninβFcRgamma assembly that recruits Syk and drives CD36/ligand internalization in macrophages. Retain receptor internalization and LDL-stimulus response with this native signaling context, not direct lipoprotein transport or uptake catalysis by Syk. Supporting Evidence: |
| GO:0005634 nucleus | ISO PMID:23071339 Serine phosphorylation by SYK is critical for nuclear locali... | KEEP AS NON CORE | Summary: Retain the mouse nuclear pool as a contextual orthology inference from SYKβIkaros cellular studies, distinct from the substrateβs own nuclear localization. Reason: Retain the mouse nuclear pool as a contextual orthology inference from SYKβIkaros cellular studies, distinct from the substrateβs own nuclear localization. PMID:23071339 examines SYKβIkaros in human cells and supports a nuclear as well as cytoplasmic pool. Retain contextual nuclear localization rather than exclude it because receptor signaling is mainly cytoplasmic. Nuclear localization of Ikaros is a separate substrate response. The preserved original source is PMID:23071339. |
| GO:0002092 positive regulation of receptor internalization | IMP PMID:22078883 CD14 controls the LPS-induced endocytosis of Toll-like recep... | KEEP AS NON CORE | Summary: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Reason: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Retain the measured receptor-traffic/interferon regulation as contextual, acknowledging opposite IFN effects in a different dendritic-cell context. |
| GO:0032481 positive regulation of type I interferon production | IMP PMID:22078883 CD14 controls the LPS-induced endocytosis of Toll-like recep... | KEEP AS NON CORE | Summary: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Reason: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Retain the measured receptor-traffic/interferon regulation as contextual, acknowledging opposite IFN effects in a different dendritic-cell context. |
| GO:0002092 positive regulation of receptor internalization | IMP PMID:23962979 The tyrosine kinase Syk differentially regulates Toll-like r... | KEEP AS NON CORE | Summary: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Reason: PMID:22078883 identifies Syk/PLCgamma2 control of CD14-dependent TLR4 endocytosis; PMID:23962979 distinguishes the associated TRAF3/TBK1/typeI-IFN branch from inhibition of TRAF6-driven cytokine signaling. Retain the measured receptor-traffic/interferon regulation as contextual, acknowledging opposite IFN effects in a different dendritic-cell context. |
| GO:0002250 adaptive immune response | ISS GO_REF:0000024 | ACCEPT | Summary: Native mouse antigen-receptor signaling and developmental genetics establish adaptive immunity participation independently of the chicken transfer. Reason: Native mouse antigen-receptor signaling and developmental genetics establish adaptive immunity participation independently of the chicken transfer. Syk supplies a catalytic signal-transmission step rather than merely a requirement inferred from lymphocyte deficiency. |
| GO:0002281 macrophage activation involved in immune response | IMP PMID:17086186 Integrin signaling in neutrophils and macrophages uses adapt... | KEEP AS NON CORE | Summary: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Reason: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Retain these native cell-type outputs outside the molecular kinase core; the IBA targetβs own experimental grounding is not circular evidence. Supporting Evidence: |
| GO:0002283 neutrophil activation involved in immune response | IMP PMID:17086186 Integrin signaling in neutrophils and macrophages uses adapt... | KEEP AS NON CORE | Summary: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Reason: PMID:17086186 directly uses mouse myeloid-cell loss and reconstitution to establish ITAM-dependent integrin activation of macrophages and neutrophils. Retain these native cell-type outputs outside the molecular kinase core; the IBA targetβs own experimental grounding is not circular evidence. Supporting Evidence: |
| GO:0007159 leukocyte cell-cell adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Reason: Retain mouse leukocyte adhesion as a conserved context with native ITAMβintegrin activation evidence; the human donor measures an adhesionβdetachment cycle. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0007229 integrin-mediated signaling pathway | IMP PMID:17086186 Integrin signaling in neutrophils and macrophages uses adapt... | ACCEPT | Summary: Native mouse integrin signaling requires Syk downstream of Src and ITAM adaptors, with direct substrate phosphorylation and deficient-cell reconstitution. Reason: Native mouse integrin signaling requires Syk downstream of Src and ITAM adaptors, with direct substrate phosphorylation and deficient-cell reconstitution. Platelet alphaIIbbeta3 and myeloid beta2-integrin contexts are supported separately. |
| GO:0030593 neutrophil chemotaxis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Reason: Retain mouse neutrophil chemotaxis as a conserved donor-supported response, without implying that the native bacterial-infection study found defective overall recruitment. Human neutrophil experiments in PMID:12885943 connect SYK to the CD18 adhesionβdetachment cycle: piceatannol increases adhesion/spreading but reduces chemotactic migration. Retain participation in adhesion and migration without converting this context into a universal positive-adhesion sign. The preserved original source is PMID:12885943. Supporting Evidence: |
| GO:0002366 leukocyte activation involved in immune response | IMP PMID:15845454 Syk-dependent cytokine induction by Dectin-1 reveals a novel... | KEEP AS NON CORE | Summary: PMID:15845454 directly shows yeast/beta-glucan Dectin1 signaling through Syk in mouse dendritic cells, with selective cytokine defects after Syk loss. Reason: PMID:15845454 directly shows yeast/beta-glucan Dectin1 signaling through Syk in mouse dendritic cells, with selective cytokine defects after Syk loss. Retain leukocyte activation/fungal-origin response as contextual, not direct fungal ligand binding by Syk. Supporting Evidence: |
| GO:0032928 regulation of superoxide anion generation | IMP PMID:19797524 Neutrophil-specific deletion of Syk kinase results in reduce... | KEEP AS NON CORE | Summary: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Reason: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Retain the specified physiological output and its assay scope; kinase signaling rather than direct bacterial killing is Sykβs own molecular contribution. Supporting Evidence: |
| GO:0042742 defense response to bacterium | IMP PMID:19797524 Neutrophil-specific deletion of Syk kinase results in reduce... | KEEP AS NON CORE | Summary: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Reason: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Retain the specified physiological output and its assay scope; kinase signaling rather than direct bacterial killing is Sykβs own molecular contribution. Supporting Evidence: |
| GO:0043313 regulation of neutrophil degranulation | IMP PMID:19797524 Neutrophil-specific deletion of Syk kinase results in reduce... | KEEP AS NON CORE | Summary: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Reason: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Retain the specified physiological output and its assay scope; kinase signaling rather than direct bacterial killing is Sykβs own molecular contribution. Supporting Evidence: |
| GO:0045087 innate immune response | IMP PMID:15845454 Syk-dependent cytokine induction by Dectin-1 reveals a novel... | ACCEPT | Summary: Syk directly transmits multiple immune receptor signals in mouse. Reason: Syk directly transmits multiple immune receptor signals in mouse. Native Dectin1-dependent cytokine signaling and integrin-dependent antimicrobial responses support innate/immune-system participation beyond B-cell signaling. The broad process remains useful across distinct receptor mechanisms. |
| GO:0050764 regulation of phagocytosis | IMP PMID:19797524 Neutrophil-specific deletion of Syk kinase results in reduce... | KEEP AS NON CORE | Summary: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Reason: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Retain the specified physiological output and its assay scope; kinase signaling rather than direct bacterial killing is Sykβs own molecular contribution. Supporting Evidence: |
| GO:0070372 regulation of ERK1 and ERK2 cascade | IMP PMID:19797524 Neutrophil-specific deletion of Syk kinase results in reduce... | KEEP AS NON CORE | Summary: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Reason: Full PMID:19797524 directly measures native mouse Syk-deficient neutrophil bacterial responses: impaired granule release, NADPH oxidase, uptake/killing and ERK/p38 activation, with reduced in vivo clearance despite normal recruitment. Retain the specified physiological output and its assay scope; kinase signaling rather than direct bacterial killing is Sykβs own molecular contribution. Supporting Evidence: |
| GO:0071226 cellular response to molecule of fungal origin | IMP PMID:15845454 Syk-dependent cytokine induction by Dectin-1 reveals a novel... | KEEP AS NON CORE | Summary: PMID:15845454 directly shows yeast/beta-glucan Dectin1 signaling through Syk in mouse dendritic cells, with selective cytokine defects after Syk loss. Reason: PMID:15845454 directly shows yeast/beta-glucan Dectin1 signaling through Syk in mouse dendritic cells, with selective cytokine defects after Syk loss. Retain leukocyte activation/fungal-origin response as contextual, not direct fungal ligand binding by Syk. Supporting Evidence: |
| GO:0002554 serotonin secretion by platelet | IMP PMID:9171347 The Fc receptor gamma-chain and the tyrosine kinase Syk are ... | KEEP AS NON CORE | Summary: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Reason: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Retain the specific platelet output in that collagen/ITAM context, without implying that Syk synthesizes secreted mediators or is required for all platelet agonists. Supporting Evidence: |
| GO:0007229 integrin-mediated signaling pathway | IMP PMID:11940607 Coordinate interactions of Csk, Src, and Syk kinases with [a... | ACCEPT | Summary: Native mouse integrin signaling requires Syk downstream of Src and ITAM adaptors, with direct substrate phosphorylation and deficient-cell reconstitution. Reason: Native mouse integrin signaling requires Syk downstream of Src and ITAM adaptors, with direct substrate phosphorylation and deficient-cell reconstitution. Platelet alphaIIbbeta3 and myeloid beta2-integrin contexts are supported separately. |
| GO:0010543 regulation of platelet activation | IMP PMID:9171347 The Fc receptor gamma-chain and the tyrosine kinase Syk are ... | KEEP AS NON CORE | Summary: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Reason: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Retain the specific platelet output in that collagen/ITAM context, without implying that Syk synthesizes secreted mediators or is required for all platelet agonists. Supporting Evidence: |
| GO:0033630 positive regulation of cell adhesion mediated by integrin | IMP PMID:11940607 Coordinate interactions of Csk, Src, and Syk kinases with [a... | KEEP AS NON CORE | Summary: Full PMID:11940607 shows that Syk-deficient mouse platelets activate Src after adhesion but fail to spread and phosphorylate downstream cytoskeletal substrates. Reason: Full PMID:11940607 shows that Syk-deficient mouse platelets activate Src after adhesion but fail to spread and phosphorylate downstream cytoskeletal substrates. Retain positive integrin-mediated adhesion/spreading regulation; static human neutrophil inhibition assays measure a distinct adhesionβdetachment context. |
| GO:0045780 positive regulation of bone resorption | IMP PMID:17353363 Syk, c-Src, the alphavbeta3 integrin, and ITAM immunorecepto... | KEEP AS NON CORE | Summary: Full PMID:17353363 identifies a Syk-dependent mature osteoclast cytoskeletal/resorptive function, with increased skeletal mass and impaired resorption after loss. Reason: Full PMID:17353363 identifies a Syk-dependent mature osteoclast cytoskeletal/resorptive function, with increased skeletal mass and impaired resorption after loss. It explicitly distinguishes diminished mature-cell activity from impaired differentiation. Retain positive bone-resorption regulation as contextual biology. Supporting Evidence: |
| GO:0090237 regulation of arachidonate secretion | IMP PMID:9171347 The Fc receptor gamma-chain and the tyrosine kinase Syk are ... | KEEP AS NON CORE | Summary: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Reason: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Retain the specific platelet output in that collagen/ITAM context, without implying that Syk synthesizes secreted mediators or is required for all platelet agonists. Supporting Evidence: |
| GO:0090330 regulation of platelet aggregation | IMP PMID:9171347 The Fc receptor gamma-chain and the tyrosine kinase Syk are ... | KEEP AS NON CORE | Summary: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Reason: PMID:9171347 directly demonstrates deficient collagen-induced secretion and aggregation in Syk-null mouse platelets while thrombin responses remain. Retain the specific platelet output in that collagen/ITAM context, without implying that Syk synthesizes secreted mediators or is required for all platelet agonists. Supporting Evidence: |
| GO:0001945 lymph vessel development | IMP PMID:12522250 Regulation of blood and lymphatic vascular separation by sig... | KEEP AS NON CORE | Summary: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Reason: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Retain vascular morphogenesis/development as contextual organismal functions without asserting cell-autonomous endothelial kinase action or turning hemorrhage alone into every angiogenic mechanism. Supporting Evidence: |
| GO:0048514 blood vessel morphogenesis | IMP PMID:12522250 Regulation of blood and lymphatic vascular separation by sig... | KEEP AS NON CORE | Summary: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Reason: PMID:12522250 directly demonstrates failed separation of blood and lymphatic networks in Syk-deficient mice and a hematopoietic signaling requirement. Retain vascular morphogenesis/development as contextual organismal functions without asserting cell-autonomous endothelial kinase action or turning hemorrhage alone into every angiogenic mechanism. Supporting Evidence: |
| GO:0018108 peptidyl-tyrosine phosphorylation | IMP PMID:16456001 Scaffolding adapter Grb2-associated binder 2 requires Syk to... | ACCEPT | Summary: Syk directly catalyzes protein tyrosine phosphorylation, including Gab2-associated Fc-epsilon-receptor signaling and Shc phosphorylation. Reason: Syk directly catalyzes protein tyrosine phosphorylation, including Gab2-associated Fc-epsilon-receptor signaling and Shc phosphorylation. The chicken transfer and mouse substrate study agree on the reaction without making every phosphorylated downstream protein a direct Syk substrate. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Mouse Syk has cytoplasmic soluble and membrane-associated signaling pools; receptor-dependent recruitment and release are directly established. Reason: Mouse Syk has cytoplasmic soluble and membrane-associated signaling pools; receptor-dependent recruitment and release are directly established. Retain the valid broad cytoplasm claim alongside cytosol and membrane annotations. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Syk is recruited peripherally to phosphorylated membrane-receptor signaling chains, supported by native mouse receptor studies and ITAM/SH2 binding. Reason: Syk is recruited peripherally to phosphorylated membrane-receptor signaling chains, supported by native mouse receptor studies and ITAM/SH2 binding. The PTN002521457 localization assertion is not a claim of integral membrane topology or exclusive membrane residence. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000043 | ACCEPT | Summary: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Reason: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Retain both broad cytoplasmic/phagocytic-vesicle and finer early-phagosome locations; membrane recruitment does not imply soluble protein inside the vesicle lumen. |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Reason: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Retain both broad cytoplasmic/phagocytic-vesicle and finer early-phagosome locations; membrane recruitment does not imply soluble protein inside the vesicle lumen. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: Syk forms multiple signaling assemblies. Reason: Syk forms multiple signaling assemblies. Full PMID:22451653 directly identifies a vitronectin-responsive Siglec15βDAP12βSyk complex in mouse osteoclasts; the human Ikaros study provides a distinct donor complex. Retain the general complex term across these architectures instead of selecting only one complex or misclassifying a true broad claim as peripheral merely for breadth. |
| GO:0042101 T cell receptor complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse TCR-complex claim is retained as conditional orthology-supported association; endogenous expression/developmental overlap with Zap70 does not make Syk a constitutive receptor subunit. Reason: The mouse TCR-complex claim is retained as conditional orthology-supported association; endogenous expression/developmental overlap with Zap70 does not make Syk a constitutive receptor subunit. PMID:8176201 explicitly reports stimulation-dependent SYK association with TCR complexes, including heterologous phosphorylated zeta-chain reconstitution. Retain this conditional receptor-associated pool; SYK is not a constitutive structural component of the antigen-binding TCR and is not interchangeable with ZAP70 in every developmental stage. The preserved original source is PMID:8176201. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9674908 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9674931 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9674959 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9674973 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9676072 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9705471 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9707972 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9707979 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-5621346 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9607032 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0032991 protein-containing complex | IDA PMID:22451653 Siglec-15 protein regulates formation of functional osteocla... | ACCEPT | Summary: Syk forms multiple signaling assemblies. Reason: Syk forms multiple signaling assemblies. Full PMID:22451653 directly identifies a vitronectin-responsive Siglec15βDAP12βSyk complex in mouse osteoclasts; the human Ikaros study provides a distinct donor complex. Retain the general complex term across these architectures instead of selecting only one complex or misclassifying a true broad claim as peripheral merely for breadth. |
| GO:0032991 protein-containing complex | ISO PMID:23071339 Serine phosphorylation by SYK is critical for nuclear locali... | ACCEPT | Summary: Syk forms multiple signaling assemblies. Reason: Syk forms multiple signaling assemblies. Full PMID:22451653 directly identifies a vitronectin-responsive Siglec15βDAP12βSyk complex in mouse osteoclasts; the human Ikaros study provides a distinct donor complex. Retain the general complex term across these architectures instead of selecting only one complex or misclassifying a true broad claim as peripheral merely for breadth. |
| GO:0005737 cytoplasm | ISO PMID:23071339 Serine phosphorylation by SYK is critical for nuclear locali... | ACCEPT | Summary: Mouse Syk has cytoplasmic soluble and membrane-associated signaling pools; receptor-dependent recruitment and release are directly established. Reason: Mouse Syk has cytoplasmic soluble and membrane-associated signaling pools; receptor-dependent recruitment and release are directly established. Retain the valid broad cytoplasm claim alongside cytosol and membrane annotations. |
| GO:0032009 early phagosome | IDA PMID:15845454 Syk-dependent cytokine induction by Dectin-1 reveals a novel... | ACCEPT | Summary: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Reason: Dectin1/Syk studies support recruitment to early phagosome-associated signaling assemblies. Retain both broad cytoplasmic/phagocytic-vesicle and finer early-phagosome locations; membrane recruitment does not imply soluble protein inside the vesicle lumen. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-442289 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0005829 cytosol | TAS Reactome:R-MMU-5607754 | ACCEPT | Summary: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Reason: Syk is a cytoplasmic non-receptor kinase with a soluble pool before/after receptor recruitment. Native mouse BCR activation/release experiments independently support cytosolic location; each Reactome entry provides a pathway-specific occurrence, not a separate native localization assay. |
| GO:0019815 B cell receptor complex | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | KEEP AS NON CORE | Summary: PMID:8626447 directly reconstitutes activation-dependent BCR association of Syk in nonlymphoid AtT20 cells. Reason: PMID:8626447 directly reconstitutes activation-dependent BCR association of Syk in nonlymphoid AtT20 cells. Retain this conditional signaling-complex membership, not constitutive antigen-binding receptor structure; catalytically inactive Syk can associate without restoring downstream signaling. Supporting Evidence: |
| GO:0042101 T cell receptor complex | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: The mouse TCR-complex claim is retained as conditional orthology-supported association; endogenous expression/developmental overlap with Zap70 does not make Syk a constitutive receptor subunit. Reason: The mouse TCR-complex claim is retained as conditional orthology-supported association; endogenous expression/developmental overlap with Zap70 does not make Syk a constitutive receptor subunit. PMID:8176201 explicitly reports stimulation-dependent SYK association with TCR complexes, including heterologous phosphorylated zeta-chain reconstitution. Retain this conditional receptor-associated pool; SYK is not a constitutive structural component of the antigen-binding TCR and is not interchangeable with ZAP70 in every developmental stage. The preserved original source is PMID:8176201. |
| GO:0030168 platelet activation | IMP PMID:9171347 The Fc receptor gamma-chain and the tyrosine kinase Syk are ... | NEW | Summary: This is an inherited proposal present in the baseline, not newly added coverage. Reason: This is an inherited proposal present in the baseline, not newly added coverage. Native mouse PMID:9171347 demonstrates that Syk executes collagen-receptor signal transmission required for platelet activation, with preserved thrombin responses delimiting its role. Preserve the historical row and original payload; do not add another redundant platelet-process proposal. Supporting Evidence: |
| GO:0038095 Fc-epsilon receptor signaling pathway | IMP PMID:9000133 Critical role for the tyrosine kinase Syk in signalling thro... | NEW | Summary: This inherited baseline proposal is retained because native mouse Syk-deficient mast cells and proximal kinase signaling establish actual Fc-epsilon-receptor pathway participation in PMID:9000133. Reason: This inherited baseline proposal is retained because native mouse Syk-deficient mast cells and proximal kinase signaling establish actual Fc-epsilon-receptor pathway participation in PMID:9000133. It is not a fresh proposal based only on mediator-release necessity, and no further ancestor/descendant proposal is added. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17086186 Integrin signaling in neutrophils and macrophages uses adapt... | MODIFY | Summary: Full PMID:17086186 uses native mouse integrin-triggered cells and Syk/DAP12 mutants to establish the requirement for Syk SH2 recognition of phosphorylated ITAM adaptors DAP12 and FcRgamma. Reason: Full PMID:17086186 uses native mouse integrin-triggered cells and Syk/DAP12 mutants to establish the requirement for Syk SH2 recognition of phosphorylated ITAM adaptors DAP12 and FcRgamma. Refine each preserved bare-binding partner to phosphotyrosine residue binding; no change is made to the original partner payloads. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22496641 CEACAM1 negatively regulates IL-1Ξ² production in LPS activat... | REMOVE | Summary: CEACAM1-associated signaling complex; bare binding is uninformative. Reason: The preserved P31809 partner is mouse CEACAM1. Full PMID:22496641 supports the LPS-induced TLR4βSYKβCEACAM1 assembly in neutrophils. Preserve that association and the original partner payload, but remove the uninformative bare binding label under repository policy; coassociation alone does not establish an isolated direct interface or a new catalytic activity. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which Syk receptor contexts in mouse should be considered core gene-product functions rather than immune-cell-specific downstream outputs?
Q: Which Syk isoform/localization differences are sufficiently supported for isoform-specific GO annotation?
Experiment: Compare kinase-dead, SH2-binding-defective, and isoform-specific Syk rescue alleles in mouse immune-cell receptor signaling assays.
Hypothesis: Syk core functions partition into phosphotyrosine docking and tyrosine kinase catalytic modules that have receptor-context-specific requirements.
Type: Genetic rescue and phosphoproteomics
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations