MAPK14 encodes p38 alpha (SAPK2a/CSBP), the prototypic and ubiquitously expressed member of the p38 subfamily of mitogen-activated protein kinases. It is a proline-directed serine/threonine kinase of the CMGC group that is activated by environmental stresses (osmotic, oxidative, UV, ribotoxic, DNA damage) and pro-inflammatory stimuli (LPS, IL-1, TNF) through dual phosphorylation of the Thr180-Gly-Tyr182 activation-loop motif by the MAP kinase kinases MKK3 and MKK6, with TAB1-driven autophosphorylation and TCR/ZAP70 Tyr323 phosphorylation as alternative routes. Docking-motif interactions direct it to substrates in the cytosol and nucleus, including the downstream kinases MK2/MK3, MSK1/MSK2, MNK1/MNK2 and MK5, transcription factors such as MEF2A/C, ATF2 and USF1, and RNA-binding proteins such as TIAR. Through these outputs p38 alpha controls inflammatory cytokine production, mRNA stability and translation, chromatin-associated gene induction, cell-cycle checkpoints, senescence, and differentiation of muscle, erythroid and other lineages. Activity is terminated by MAPK phosphatases (DUSP1, DUSP10, DUSP16, PTPRR, PPM1D). p38 alpha is the target of the pyridinyl-imidazole cytokine-suppressive anti-inflammatory drugs (e.g. SB203580).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | ISS GO_REF:0000024 | ACCEPT | Summary: MAPK cascade by similarity to mouse p38alpha. Reason: Correct; the more specific p38MAPK cascade (GO:0038066) is also annotated. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0002862 negative regulation of inflammatory response to antigenic stimulus | TAS Reactome:R-HSA-9662834 | MARK AS OVER ANNOTATED | Summary: Reactome 'CD163 mediating an anti-inflammatory response' includes p38alpha phosphorylation of ADAM17, which sheds CD163. Reason: MAPK14 is overwhelmingly a pro-inflammatory kinase; its inclusion here reflects ADAM17 phosphorylation within a pathway diagram, not a demonstrated role in negatively regulating inflammatory responses to antigen. Supporting Evidence: Reactome:R-HSA-9662834 sCD163 is formed from the increased shedding of CD163 mediated by the tumor necrosis factor-Ξ± (TNF-Ξ±) cleaving enzyme, ADAM17 file:human/MAPK14/MAPK14-uniprot.txt In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:11532965 The Usf-1 transcription factor is a novel target for the str... | ACCEPT | Summary: p38 phosphorylates the transcription factor USF1 (Thr153) in UV-stressed melanocytic cells. Reason: Direct in vitro/in vivo phosphorylation of USF1 by p38alpha supports Ser/Thr kinase activity. Supporting Evidence: PMID:11532965 Consistent with this we demonstrate that Usf-1 is phosphorylated and activated by the stress-responsive p38 kinase. PMID:11532965 consistent with Thr153 being a target for p38-mediated phosphorylation of Usf-1 |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: MAPK14 is a protein serine/threonine kinase; PAINT places this function at the ancestral node of the MAP kinase family. Reason: Correct and phylogenetically sound; MAP kinase activity (GO:0004707) is the more specific child that MAPK14 also carries. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. file:human/MAPK14/MAPK14-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:35857590 ZAKΞ±-driven ribotoxic stress response activates the human NL... | ACCEPT | Summary: p38alpha directly phosphorylates the NLRP1 disordered linker in vitro, downstream of ZAKalpha in the ribotoxic stress response. Reason: Direct in vitro kinase activity towards a physiological substrate. Supporting Evidence: PMID:35857590 Both p38Ξ± and p38Ξ² could phosphorylate recombinant NLRP1DR, including residues within the ZAKΞ± motifs file:human/MAPK14/MAPK14-uniprot.txt Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:7535770 Pro-inflammatory cytokines and environmental stress cause p3... | ACCEPT | Summary: Mutation of the Thr180/Tyr182 dual-phosphorylation sites abolishes p38 activation and kinase activity. Reason: Classic characterisation of p38 as a dual-phosphorylation-activated MAP kinase; kinase activity is the core function. Supporting Evidence: PMID:7535770 The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. PMID:7535770 Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-198669 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates MSK1. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-198669 It can be activated 5-fold by p38MAPK through phosphorylation at four key residues. file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-428961 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates cPLA2. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-428961 MAPK p38 alpha activates cPLA2 by phosphorylation of two serine residues. file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-448955 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates MEF2A/MEF2C. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-448955 MEF2A and MEF2C are preferred substrates for p38 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-450222 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates MAPKAPK2/3. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-450222 Upon activation, p38 MAPK alpha activates MK2 by phosphorylating Thr-222, Ser-272, and Thr-334 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9626880 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates NCF1/p47phox Ser345. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-9626880 MAPK11 or MAPK14 phosphorylates NCF1 at Ser345 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9662823 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates ADAM17. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-9662823 PLK2, MAPK14 phosphorylate ADAM17 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9942578 | ACCEPT | Summary: Reactome reaction in which active p38alpha phosphorylates CDC25A. Reason: Ser/Thr phosphorylation of downstream substrates is the core catalytic function of MAPK14; GO:0004707 MAP kinase activity is the more specific term also annotated. Supporting Evidence: Reactome:R-HSA-9942578 p38 MAPK (MAPK14) phosphorylates full-length CDC25A in vitro on serine residues S76 and S124 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004707 MAP kinase activity | IDA PMID:10330143 Targeting of p38 mitogen-activated protein kinases to MEF2 t... | ACCEPT | Summary: p38alpha phosphorylates and activates MEF2A and MEF2C in a docking-domain-dependent manner. Reason: Direct experimental support for the core catalytic activity of MAPK14 as a MAP kinase. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 |
| GO:0004707 MAP kinase activity | IDA PMID:20932473 DNA damage activates a spatially distinct late cytoplasmic c... | ACCEPT | Summary: p38 directly phosphorylates TIAR in vitro, releasing Gadd45alpha mRNA during DNA-damage checkpoint maintenance. Reason: Direct experimental support for the core catalytic activity of MAPK14 as a MAP kinase. Supporting Evidence: PMID:20932473 However, we did observe strong direct phosphorylation of TIAR by p38 in vitro file:human/MAPK14/MAPK14-uniprot.txt Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation |
| GO:0004707 MAP kinase activity | IDA PMID:7997261 A protein kinase involved in the regulation of inflammatory ... | ACCEPT | Summary: Identification of p38alpha (CSBP) as a MAP kinase homologue whose kinase activity is inhibited by pyridinyl-imidazole CSAIDs. Reason: Direct experimental support for the core catalytic activity of MAPK14 as a MAP kinase. Supporting Evidence: PMID:7997261 Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: MAP kinase activity inferred from InterPro MAP kinase signatures and EC 2.7.11.24. Reason: Correct and the most informative MF for MAPK14. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0004708 MAP kinase kinase activity | TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ... | REMOVE | Summary: MAP kinase kinase activity attributed to p38 from an eosinophil study of eotaxin signalling. Reason: p38alpha is a MAP kinase, not a MAP kinase kinase: it is itself phosphorylated by MKK3/MKK6 and phosphorylates Ser/Thr-Pro sites in downstream proteins. The cited study measured activation of ERK2 and p38 and used pharmacological inhibitors; it does not show that p38 phosphorylates and activates another MAPK. This TAS is a term-selection error. Supporting Evidence: PMID:10706854 We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:10601328 A novel regulatory mechanism of MAP kinases activation and n... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase PTPRR/PTP-SL (WITH/FROM UniProtKB:Q15256), reported in this study. Reason: The partner PTPRR/PTP-SL is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:10601328 Upon phosphorylation of Ser(231), PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal-regulated kinase (ERK)1/2 and p38alpha were impaired. file:human/MAPK14/MAPK14-uniprot.txt Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:11238443 Stress-induced inhibition of ERK1 and ERK2 by direct interac... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPK3/ERK1 (WITH/FROM UniProtKB:P27361), reported in this study. Reason: Bare protein binding is uninformative. The partner MAPK3/ERK1 is a protein kinase; the interaction has no established functional role, but the partner identity supports the more informative MF, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:11238443 We have identified a direct physical interaction between the stress signaling p38alpha MAP kinase and the mitogen-activated protein kinases ERK1 and ERK2 by affinity chromatography and coimmunoprecipitation studies. file:human/MAPK14/MAPK14-uniprot.txt Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: MAPK14 interacts with ZFP36L1 (WITH/FROM UniProtKB:Q07352), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:16189514 Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. |
| GO:0005515 protein binding | IPI PMID:16751104 p38 and a p38-interacting protein are critical for downregul... | REMOVE | Summary: MAPK14 interacts with SUPT20H/p38IP (WITH/FROM UniProtKB:Q8NEM7), reported in this study. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). p38IP/SUPT20H binds p38 directly and is required for its activation in vivo, but no specific MF term describes the MAPK14 side of this interaction. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:16751104 We show that p38IP binds directly to p38 and is required for p38 activation in vivo. |
| GO:0005515 protein binding | IPI PMID:17255097 Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodim... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in this study. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:17255097 The C-terminal regulatory domain of MK2 binds in the docking groove of p38alpha, and the ATP-binding sites of both kinases are at the heterodimer interface. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:17255949 Mxi2 promotes stimulus-independent ERK nuclear translocation... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K3/MKK3 (WITH/FROM UniProtKB:P46734), reported in this study. Reason: MAP2K3/MKK3 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:17255949 Mxi2 accumulation in the nucleus is not due to its inability to interact with putative cytoplasmic anchors, as Mxi2 is capable of interacting with MKK 3 and 6. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:17255949 Mxi2 promotes stimulus-independent ERK nuclear translocation... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K6/MKK6 (WITH/FROM UniProtKB:P52564), reported in this study. Reason: MAP2K6/MKK6 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:17255949 Mxi2 accumulation in the nucleus is not due to its inability to interact with putative cytoplasmic anchors, as Mxi2 is capable of interacting with MKK 3 and 6. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:17380123 A new p38 MAP kinase-regulated transcriptional coactivator t... | REMOVE | Summary: MAPK14 interacts with ZNHIT1/p18Hamlet (WITH/FROM UniProtKB:O43257), reported in this study. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). p18Hamlet/ZNHIT1 is a p38-regulated protein and candidate substrate; the relationship belongs on the kinase activity as has_input. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:17380123 We have identified a new p38 MAPK-regulated protein that we named p18(Hamlet) |
| GO:0005515 protein binding | IPI PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple... | REMOVE | Summary: MAPK14 interacts with RB1 (WITH/FROM UniProtKB:P06400), reported in this study. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Rb is a p38 substrate (Ser567 phosphorylation), which is better represented as has_input on the kinase activity than as a binding MF. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:17380128 Here, we report that DNA damage induced not only the dephosphorylation of pRB at Cdk phosphorylation sites and the binding of pRB to E2F-1, but also the phosphorylation of pRB at Ser612. |
| GO:0005515 protein binding | IPI PMID:18624398 Protein interaction data set highlighted with human Ras-MAPK... | REMOVE | Summary: MAPK14 interacts with ZNHIT1/p18Hamlet (WITH/FROM UniProtKB:O43257), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). p18Hamlet/ZNHIT1 is a p38-regulated protein and candidate substrate; the relationship belongs on the kinase activity as has_input. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:18624398 Here we report on yeast two hybrid screening results of a protein interaction network around the known components of human Ras-MAPK/PI3K pathways. |
| GO:0005515 protein binding | IPI PMID:18624398 Protein interaction data set highlighted with human Ras-MAPK... | REMOVE | Summary: MAPK14 interacts with EEF1A1 (WITH/FROM UniProtKB:P68104), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:18624398 Here we report on yeast two hybrid screening results of a protein interaction network around the known components of human Ras-MAPK/PI3K pathways. |
| GO:0005515 protein binding | IPI PMID:20347885 DUSP26 negatively affects the proliferation of epithelial ce... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP1/MKP-1 (WITH/FROM UniProtKB:P28562), reported in this study. Reason: The partner DUSP1/MKP-1 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:20347885 DUSP26 does not act as a dual specificity phosphatase on ERK, JNK or p38 MAPKs file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:20368287 Interactome mapping of the phosphatidylinositol 3-kinase-mam... | REMOVE | Summary: MAPK14 interacts with TSC1 (WITH/FROM UniProtKB:Q92574), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:20368287 we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway |
| GO:0005515 protein binding | IPI PMID:20871633 p38 phosphorylates Rb on Ser567 by a novel, cell cycle-indep... | REMOVE | Summary: MAPK14 interacts with RB1 (WITH/FROM UniProtKB:P06400), reported in this study. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Rb is a p38 substrate (Ser567 phosphorylation), which is better represented as has_input on the kinase activity than as a binding MF. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:20871633 p38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates Rb on Ser567, which is not phosphorylated during the normal cell cycle. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA5/MSK1 (WITH/FROM UniProtKB:O75582), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA5/MSK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP1/MKP-1 (WITH/FROM UniProtKB:P28562), reported in a high-throughput interaction screen. Reason: The partner DUSP1/MKP-1 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: MAPK14 interacts with MIDEAS/ELMSAN1 (WITH/FROM UniProtKB:Q6PJG2), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: MAPK14 interacts with SUPT20H/p38IP (WITH/FROM UniProtKB:Q8NEM7), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). p38IP/SUPT20H binds p38 directly and is required for its activation in vivo, but no specific MF term describes the MAPK14 side of this interaction. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK1/MNK1 (WITH/FROM UniProtKB:Q9BUB5), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK1/MNK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP16/MKP-7 (WITH/FROM UniProtKB:Q9BY84), reported in a high-throughput interaction screen. Reason: The partner DUSP16/MKP-7 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK2/MNK2 (WITH/FROM UniProtKB:Q9HBH9), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK2/MNK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20936779 Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:21283629 LZAP inhibits p38 MAPK (p38) phosphorylation and activity by... | REMOVE | Summary: MAPK14 interacts with CDK5RAP3/LZAP (WITH/FROM UniProtKB:Q96JB5), reported in this study. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). LZAP binds p38 and promotes WIP1 association, but LZAP is not an established scaffold protein, so no more specific MF can be asserted for MAPK14. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:21283629 Here we show that the LZAP binds p38, alters p38 cellular localization, and inhibits basal and cytokine-stimulated p38 activity. |
| GO:0005515 protein binding | IPI PMID:21908610 Phosphorylation of the kinase interaction motif in mitogen-a... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP9/MKP-4 (WITH/FROM UniProtKB:Q99956), reported in this study. Reason: The partner DUSP9/MKP-4 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:21908610 unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38Ξ± MAP kinase both in vitro and in vivo file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:21988832 we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: MAPK14 interacts with SUPT20H/p38IP (WITH/FROM UniProtKB:Q8NEM7), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). p38IP/SUPT20H binds p38 directly and is required for its activation in vivo, but no specific MF term describes the MAPK14 side of this interaction. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:21988832 we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology |
| GO:0005515 protein binding | IPI PMID:23397142 Analysis of protein-protein interactions in cross-talk pathw... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPK3/ERK1 (WITH/FROM UniProtKB:P27361), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPK3/ERK1 is a protein kinase; the interaction has no established functional role, but the partner identity supports the more informative MF, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23397142 We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways file:human/MAPK14/MAPK14-uniprot.txt Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23455922 We systematically investigated the reproducibility of a standardized AP-MS workflow by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human kinases. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23455922 We systematically investigated the reproducibility of a standardized AP-MS workflow by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human kinases. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK1/MNK1 (WITH/FROM UniProtKB:Q9BUB5), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK1/MNK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23455922 We systematically investigated the reproducibility of a standardized AP-MS workflow by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human kinases. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:23560844 Metal-dependent protein phosphataseΒ 1A functions as an extra... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase PPM1A/PP2C-alpha (WITH/FROM UniProtKB:P35813), reported in this study. Reason: The partner PPM1A/PP2C-alpha is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:23560844 Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K3/MKK3 (WITH/FROM UniProtKB:P46734), reported in a high-throughput interaction screen. Reason: MAP2K3/MKK3 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK1/MNK1 (WITH/FROM UniProtKB:Q9BUB5), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK1/MNK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK2/MNK2 (WITH/FROM UniProtKB:Q9HBH9), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK2/MNK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP1/MKP-1 (WITH/FROM UniProtKB:P28562), reported in a high-throughput interaction screen. Reason: The partner DUSP1/MKP-1 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK2/MNK2 (WITH/FROM UniProtKB:Q9HBH9), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK2/MNK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25241761 employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25852190 We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26496610 Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26496610 Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP1/MKP-1 (WITH/FROM UniProtKB:P28562), reported in a high-throughput interaction screen. Reason: The partner DUSP1/MKP-1 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:27880917 we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP9/MKP-4 (WITH/FROM UniProtKB:Q99956), reported in a high-throughput interaction screen. Reason: The partner DUSP9/MKP-4 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:27880917 we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP16/MKP-7 (WITH/FROM UniProtKB:Q9BY84), reported in a high-throughput interaction screen. Reason: The partner DUSP16/MKP-7 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:27880917 we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31515488 we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K3/MKK3 (WITH/FROM UniProtKB:P46734), reported in a high-throughput interaction screen. Reason: MAP2K3/MKK3 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: MAPK14 interacts with EEF1A1 (WITH/FROM UniProtKB:P68104), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K3/MKK3 (WITH/FROM UniProtKB:P46734), reported in a high-throughput interaction screen. Reason: MAP2K3/MKK3 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K6/MKK6 (WITH/FROM UniProtKB:P52564), reported in a high-throughput interaction screen. Reason: MAP2K6/MKK6 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP9/MKP-4 (WITH/FROM UniProtKB:Q99956), reported in a high-throughput interaction screen. Reason: The partner DUSP9/MKP-4 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK1/MNK1 (WITH/FROM UniProtKB:Q9BUB5), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK1/MNK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK2/MNK2 (WITH/FROM UniProtKB:Q9HBH9), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK2/MNK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:32707033 Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: MAPK14 interacts with the protein kinase CSNK1D (casein kinase 1 delta, isoform 2) (WITH/FROM UniProtKB:P48730-2), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner CSNK1D (casein kinase 1 delta, isoform 2) is a protein kinase; the interaction has no established functional role, but the partner identity supports the more informative MF, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. file:human/MAPK14/MAPK14-uniprot.txt Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA5/MSK1 (WITH/FROM UniProtKB:O75582), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA5/MSK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with its upstream activating MAP kinase kinase MAP2K3/MKK3 (WITH/FROM UniProtKB:P46734), reported in a high-throughput interaction screen. Reason: MAP2K3/MKK3 is one of the two canonical MAP2Ks that dually phosphorylate p38alpha on the TGY motif. Replace bare protein binding with 'mitogen-activated protein kinase kinase binding', matching the MAPK1 review. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase PTPRR/PTP-SL (WITH/FROM UniProtKB:Q15256), reported in a high-throughput interaction screen. Reason: The partner PTPRR/PTP-SL is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP7/PYST2 (WITH/FROM UniProtKB:Q16829), reported in a high-throughput interaction screen. Reason: The partner DUSP7/PYST2 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: MAPK14 interacts with MIDEAS/ELMSAN1 (WITH/FROM UniProtKB:Q6PJG2), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP9/MKP-4 (WITH/FROM UniProtKB:Q99956), reported in a high-throughput interaction screen. Reason: The partner DUSP9/MKP-4 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK1/MNK1 (WITH/FROM UniProtKB:Q9BUB5), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK1/MNK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP16/MKP-7 (WITH/FROM UniProtKB:Q9BY84), reported in a high-throughput interaction screen. Reason: The partner DUSP16/MKP-7 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: MAPK14 interacts with the protein kinase MKNK2/MNK2 (WITH/FROM UniProtKB:Q9HBH9), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MKNK2/MNK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. file:human/MAPK14/MAPK14-uniprot.txt MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: MAPK14 interacts with FBXW7 (WITH/FROM UniProtKB:Q969H0), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:35512704 Here, we identify prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a quantitative high-throughput differential screening (qHT-dS) platform. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA5/MSK1 (WITH/FROM UniProtKB:O75582), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA5/MSK1 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK2/MK2 (WITH/FROM UniProtKB:P49137), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK2/MK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: MAPK14 interacts with the protein kinase MAPKAPK3/MK3 (WITH/FROM UniProtKB:Q16644), reported in a high-throughput interaction screen. Reason: Bare protein binding is uninformative. The partner MAPKAPK3/MK3 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. file:human/MAPK14/MAPK14-uniprot.txt two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: MAPK14 interacts with MIDEAS/ELMSAN1 (WITH/FROM UniProtKB:Q6PJG2), reported in a high-throughput interaction screen. Reason: Generic protein binding is uninformative and there is no evidence-backed, more specific MF for this partner (not a kinase, MAP2K or phosphatase). Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP16/MKP-7 (WITH/FROM UniProtKB:Q9BY84), reported in a high-throughput interaction screen. Reason: The partner DUSP16/MKP-7 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:9788880 Isolation of the human genes encoding the pyst1 and Pyst2 ph... | MODIFY | Summary: MAPK14 interacts with the protein phosphatase DUSP7/PYST2 (WITH/FROM UniProtKB:Q16829), reported in this study. Reason: The partner DUSP7/PYST2 is a MAPK-directed phosphatase; phosphatases that dock onto p38alpha (via kinase interaction motifs for DUSPs/PTPRR) dephosphorylate the activation loop and terminate signalling. 'protein phosphatase binding' is the informative MF, matching the MAPK1 review. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:9788880 Pyst2 binds p42 MAP kinase in vivo and both MAP kinase binding and substrate selectivity correlate with the ability of different recombinant MAP and SAP kinases to cause catalytic activation of the Pyst2 phosphatase in vitro. file:human/MAPK14/MAPK14-deep-research-falcon.md Activity ends when activation-loop phosphates are removed. |
| GO:0005515 protein binding | IPI PMID:9792677 RSK-B, a novel ribosomal S6 kinase family member, is a CREB ... | MODIFY | Summary: MAPK14 interacts with the protein kinase RPS6KA4/MSK2 (WITH/FROM UniProtKB:O75676), reported in this study. Reason: Bare protein binding is uninformative. The partner RPS6KA4/MSK2 is a protein kinase; it is a well-established direct p38alpha substrate that docks onto the p38 docking groove, so 'protein kinase binding' is the appropriate replacement. The downstream kinase relationship itself is better captured as has_input on MAP kinase activity. Proposed replacements: protein kinase binding Supporting Evidence: PMID:9792677 RSK-B is a p38alphaMAPK substrate, and activated by p38alphaMAPK and, more weakly, by ERK1. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding inferred from the protein kinase ATP-binding signature. Reason: MAPK14 binds ATP in the interlobe cleft as the phosphate donor; correct, though subsumed by kinase activity. Supporting Evidence: file:human/MAPK14/MAPK14-deep-research-falcon.md ATP binds in the interlobe cleft |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Reactome neutrophil degranulation proteomics lists MAPK14 among proteins in granule lumen/extracellular release. Reason: MAPK14 is a soluble cytosolic/nuclear kinase with no signal peptide; detection in granule/secretome proteomics does not establish a functional extracellular or granule-lumen location. Same treatment as the MAPK1 review. Supporting Evidence: Reactome:R-HSA-6798748 Exocytosis of secretory granule lumen proteins file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Reactome neutrophil degranulation proteomics lists MAPK14 among proteins in granule lumen/extracellular release. Reason: MAPK14 is a soluble cytosolic/nuclear kinase with no signal peptide; detection in granule/secretome proteomics does not establish a functional extracellular or granule-lumen location. Same treatment as the MAPK1 review. Supporting Evidence: Reactome:R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005634 nucleus | EXP PMID:7535770 Pro-inflammatory cytokines and environmental stress cause p3... | ACCEPT | Summary: Immunofluorescence shows p38 in both the nucleus and cytoplasm of activated cells. Reason: Direct experimental localization; consistent with nuclear substrates (MEF2, ATF2, MSK1/2). Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization of MAPK14 (IBA). Reason: p38alpha shuttles between cytoplasm and nucleus and phosphorylates nuclear transcription factors; nuclear localization is well established. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005634 nucleus | IDA PMID:30878395 MicroRNA-143-3p promotes human cardiac fibrosis via targetin... | ACCEPT | Summary: Nuclear localization of p38 reported in human cardiac fibroblasts in a study of miR-143-3p/SPRY3 in cardiac fibrosis (curated by UniProt). Reason: The cached abstract does not describe the localization data, but nuclear localization of MAPK14 is independently well established; defer to the UniProt curator. Supporting Evidence: PMID:30878395 MicroRNA-143-3p promotes human cardiac fibrosis via targeting sprouty3 after myocardial infarction. PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization of MAPK14 (IEA). Reason: p38alpha shuttles between cytoplasm and nucleus and phosphorylates nuclear transcription factors; nuclear localization is well established. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear localization of MAPK14 (ISS). Reason: p38alpha shuttles between cytoplasm and nucleus and phosphorylates nuclear transcription factors; nuclear localization is well established. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-168053 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Phosphorylated MAPKs phosphorylate ATF-2'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-168053 Phosphorylated MAPKs phosphorylate ATF-2 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-198669 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'p38MAPK phosphorylates MSK1'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-198669 p38MAPK phosphorylates MSK1 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3229102 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'p-MAPKAPK3 phosphorylates BMI1'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-3229102 p-MAPKAPK3 phosphorylates BMI1 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3238999 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK5'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-3238999 Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK5 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3239014 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'MAPKAPK5 phosphorylates TP53'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-3239014 MAPKAPK5 phosphorylates TP53 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3239019 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Active p38 MAPK phosphorylates MAPKAPK5'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-3239019 Active p38 MAPK phosphorylates MAPKAPK5 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-448955 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Phosphorylation of MEF2 proteins by p38'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-448955 Phosphorylation of MEF2 proteins by p38 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-448958 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Nuclear translocation of p38 MAPK'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-448958 Nuclear translocation of p38 MAPK file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450222 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Active p38 MAPK phosphorylates MAPKAPK2 or 3'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-450222 Active p38 MAPK phosphorylates MAPKAPK2 or 3 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450257 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-450257 Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450333 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK2'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-450333 Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK2 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9855910 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'USF1 is phosphorylated by p-MAPK14'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9855910 USF1 is phosphorylated by p-MAPK14 file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9942578 | ACCEPT | Summary: Reactome places MAPK14 in the nucleoplasm in the reaction 'Phosphorylation of CDC25A by p38 MAPK'. Reason: Nuclear p38alpha phosphorylates transcription factors and nuclear kinases; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9942578 Phosphorylation of CDC25A by p38 MAPK file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0005737 cytoplasm | EXP PMID:7535770 Pro-inflammatory cytokines and environmental stress cause p3... | ACCEPT | Summary: Immunofluorescence shows p38 in both the nucleus and cytoplasm of activated cells. Reason: Direct experimental localization; many p38alpha substrates (MK2, TIAR, cPLA2) are cytoplasmic. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization of MAPK14 (IBA). Reason: p38alpha is a soluble cytoplasmic/nuclear kinase; cytoplasm is correct. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization of MAPK14 (IEA). Reason: p38alpha is a soluble cytoplasmic/nuclear kinase; cytoplasm is correct. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization of MAPK14 (ISS). Reason: p38alpha is a soluble cytoplasmic/nuclear kinase; cytoplasm is correct. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence places MAPK14 in the cytosol. Reason: Consistent with the known cytosolic pool of p38alpha. Supporting Evidence: file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. |
| GO:0005829 cytosol | IDA PMID:7535770 Pro-inflammatory cytokines and environmental stress cause p3... | ACCEPT | Summary: p38 is present and active in the cytoplasm/cytosol of activated cells. Reason: Cytosol is where p38alpha phosphorylates MK2, TIAR and other cytoplasmic substrates. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-187688 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'p38 MAPK phosphorylates MAPKAPK2, MAPKAPK3'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-187688 p38 MAPK phosphorylates MAPKAPK2, MAPKAPK3 file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-428941 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'P2Y purinoceptor 1 activates MAP kinase p38 alpha'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-428941 P2Y purinoceptor 1 activates MAP kinase p38 alpha file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-428961 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'Phosphorylation of cPLA2 by MAPK p38 alpha'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-428961 Phosphorylation of cPLA2 by MAPK p38 alpha file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432148 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'Fgr may phosphorylate p38 MAPK'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-432148 Fgr may phosphorylate p38 MAPK file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448958 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'Nuclear translocation of p38 MAPK'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-448958 Nuclear translocation of p38 MAPK file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450257 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-450257 Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2 file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5218804 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'p38 MAPK activation by VEGFR'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-5218804 p38 MAPK activation by VEGFR file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9626880 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'MAPK11 or MAPK14 phosphorylates NCF1 at Ser345'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-9626880 MAPK11 or MAPK14 phosphorylates NCF1 at Ser345 file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9662823 | ACCEPT | Summary: Reactome places MAPK14 in the cytosol in the reaction 'PLK2, MAPK14 phosphorylate ADAM17'. Reason: Cytosolic localization of p38alpha is well established. Supporting Evidence: Reactome:R-HSA-9662823 PLK2, MAPK14 phosphorylate ADAM17 file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0006357 regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II by similarity to mouse p38alpha. Reason: A principal output of nuclear p38alpha is phosphorylation and activation of Pol II transcription factors (MEF2A/C, ATF2, USF1) and of the MSK1/2 kinases that target CREB and chromatin; this is a direct, core consequence of its kinase activity. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. PMID:11532965 Consistent with this we demonstrate that Usf-1 is phosphorylated and activated by the stress-responsive p38 kinase. |
| GO:0006935 chemotaxis | TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ... | KEEP AS NON CORE | Summary: Eotaxin-induced eosinophil chemotaxis is inhibited by the p38 inhibitor SB202190. Reason: Supported by inhibitor data (SB202190 hits p38alpha and p38beta); a downstream cell-type-specific outcome of p38 signalling. Supporting Evidence: PMID:10706854 PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis. file:human/MAPK14/MAPK14-deep-research-falcon.md Claims should be considered MAPK14 specific only when supported by isoform-selective genetics, validated selective inhibitors, or direct biochemical assays. |
| GO:0007165 signal transduction | TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ... | MODIFY | Summary: Eotaxin-induced activation of p38 in eosinophils. Reason: Signal transduction is too general; the paper shows eotaxin/CCR3-triggered p38 activation, i.e. the p38MAPK cascade. Proposed replacements: p38MAPK cascade Supporting Evidence: PMID:10706854 We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion. |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ... | KEEP AS NON CORE | Summary: p38 is activated downstream of the chemokine receptor CCR3 in eosinophils. Reason: p38alpha does act downstream of many cell-surface receptors, but receptor signalling pathways are contexts rather than its core function. Supporting Evidence: PMID:10706854 We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion. |
| GO:0010628 positive regulation of gene expression | IGI PMID:24299952 TNFΞ± induces the expression of genes associated with endothe... | MARK AS OVER ANNOTATED | Summary: TNF-alpha down-regulates miR-149 in endothelial cells via p38, derepressing MMP-9, iNOS and IL-6. Reason: Very general term supported by an inhibitor-based endpoint several steps downstream of p38 activity. Supporting Evidence: PMID:24299952 This effect was significantly abolished in Eahy926 by treatment with p38MAPK inhibitor. |
| GO:0010628 positive regulation of gene expression | IMP PMID:25754930 Up-regulation of galectin-9 induces cell migration in human ... | MARK AS OVER ANNOTATED | Summary: Dengue virus-induced galectin-9 expression requires p38. Reason: Very general term supported by inhibitor data; not informative about MAPK14 function. Supporting Evidence: PMID:25754930 Blocking p38, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase (ERK), inhibited DV-induced expression of Gal-9. |
| GO:0010831 positive regulation of myotube differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of myotube differentiation by similarity to mouse p38alpha (P47811). Reason: Mouse p38alpha is required for myoblast differentiation/fusion via MEF2 and chromatin regulation; transfer to human is reasonable but this is a downstream developmental role. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 Reactome:R-HSA-448958 Activated p38 MAPK may translocate into the nucleus to further activate myogenic related transcription factors. |
| GO:0016607 nuclear speck | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence reports MAPK14 in nuclear speckles. Reason: Antibody-based single-source localization; plausible given the nuclear pool of p38alpha, but not a characterised site of p38 function. Supporting Evidence: PMID:7535770 Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. |
| GO:0019899 enzyme binding | IPI PMID:23483889 Protein arginine methyltransferase 1 interacts with and acti... | KEEP AS NON CORE | Summary: p38alpha binds the arginine methyltransferase PRMT1, which methylates and activates it. Reason: Enzyme binding is broad but accurate (PRMT1 is an enzyme that modifies p38alpha); this is a regulatory interaction, not a core MF. Supporting Evidence: PMID:23483889 Together, our results suggest that PRMT1 may enhance the activation of p38Ξ± by directly binding to and methylating p38Ξ±. |
| GO:0019903 protein phosphatase binding | IPI PMID:10391943 Molecular cloning and characterization of a novel dual speci... | ACCEPT | Summary: p38 binds and is inactivated by the dual-specificity phosphatase MKP-5/DUSP10, for which p38 is a preferred substrate. Reason: Direct binding to its negative-regulatory phosphatase; informative MF. Supporting Evidence: PMID:10391943 MKP-5 binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. file:human/MAPK14/MAPK14-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. |
| GO:0019903 protein phosphatase binding | IPI PMID:21283629 LZAP inhibits p38 MAPK (p38) phosphorylation and activity by... | ACCEPT | Summary: p38 associates with the PP2C phosphatase WIP1/PPM1D, an interaction enhanced by LZAP. Reason: WIP1 dephosphorylates and inactivates p38; protein phosphatase binding is the informative MF. Supporting Evidence: PMID:21283629 Expression of LZAP increased both LZAP and Wip1 binding to p38. file:human/MAPK14/MAPK14-uniprot.txt PPM1D also mediates dephosphorylation and inactivation of MAPK14 |
| GO:0030168 platelet activation | TAS Reactome:R-HSA-418592 | KEEP AS NON CORE | Summary: Reactome 'ADP signalling through P2Y purinoceptor 1': P2Y1 activates p38alpha, which phosphorylates cPLA2 in platelets. Reason: p38alpha contributes to platelet signalling (cPLA2 phosphorylation); a cell-type context of the p38 cascade. Supporting Evidence: Reactome:R-HSA-428941 These effects are partly mediated by the P2Y1 purinocetor, inducing p38 MAP kinase activation via an uncharacterised factor. |
| GO:0030316 osteoclast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Osteoclast differentiation by similarity to mouse p38alpha. Reason: Mouse genetic studies implicate p38alpha in RANKL-driven osteoclastogenesis; a cell-type-specific downstream role. Supporting Evidence: file:human/MAPK14/MAPK14-deep-research-falcon.md Outcomes can be opposite in different cells |
| GO:0031098 stress-activated protein kinase signaling cascade | IDA PMID:35857590 ZAKΞ±-driven ribotoxic stress response activates the human NL... | ACCEPT | Summary: Stress-activated protein kinase signalling downstream of ZAKalpha in UVB-induced ribotoxic stress. Reason: Correct; parent of stress-activated MAPK cascade. Supporting Evidence: PMID:35857590 UVB induced bona fide RSR activation in N/TERT keratinocytes marked by ZAKΞ±, p38 and JNK phosphorylation at earlier time points |
| GO:0031281 positive regulation of cyclase activity | IMP PMID:22027397 HIV-1 and IL-1Ξ² regulate astrocytic CD38 through mitogen-act... | MARK AS OVER ANNOTATED | Summary: IL-1beta-induced CD38 expression and ADP-ribosyl cyclase activity in astrocytes is reduced by p38 inhibition. Reason: The effect is on CD38 expression (transcriptional), not direct regulation of cyclase catalytic activity; inhibitor-based and several steps removed from p38 kinase function. Supporting Evidence: PMID:22027397 The IL-1Ξ²-induced ADP-ribosyl cyclase activity of CD38 was also significantly reduced by inhibition of each of the p38Ks, JNK and ERK pathways. PMID:22027397 Thus, activation of p38Ks, JNK and ERK MAPKs likely contribute to increased CD38 mRNA expression in IL-1Ξ²-activated astrocytes. |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of IL-12 production inferred by ARBA. Reason: p38 regulates IL-12p40 production in dendritic cells/macrophages; downstream immune outcome. Supporting Evidence: PMID:25754930 DV infection-induced production of IL-12 was Gal-9- and p38-dependent. |
| GO:0032735 positive regulation of interleukin-12 production | IMP PMID:25754930 Up-regulation of galectin-9 induces cell migration in human ... | KEEP AS NON CORE | Summary: Dengue virus-induced IL-12 production in human dendritic cells depends on p38. Reason: Downstream immune outcome supported by inhibitor data; non-core. Supporting Evidence: PMID:25754930 DV infection-induced production of IL-12 was Gal-9- and p38-dependent. file:human/MAPK14/MAPK14-deep-research-falcon.md Claims should be considered MAPK14 specific only when supported by isoform-selective genetics, validated selective inhibitors, or direct biochemical assays. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Reactome neutrophil degranulation proteomics lists MAPK14 among proteins in granule lumen/extracellular release. Reason: MAPK14 is a soluble cytosolic/nuclear kinase with no signal peptide; detection in granule/secretome proteomics does not establish a functional extracellular or granule-lumen location. Same treatment as the MAPK1 review. Supporting Evidence: Reactome:R-HSA-6798748 Exocytosis of secretory granule lumen proteins file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:0035331 negative regulation of hippo signaling | IMP PMID:27402810 Regulation of Hippo signalling by p38 signalling. | KEEP AS NON CORE | Summary: p38 signalling regulates Hippo signalling in Drosophila and mammalian cells; siRNA against p38alpha reduces CTGF/Cyr61 transcription in A549 cells. Reason: Supported by knockdown data; a context-dependent crosstalk role rather than a core function. Supporting Evidence: PMID:27402810 Indeed, transcription of CTGF and Cyr61 was downregulated by siRNAs targeting p38Ξ± PMID:27402810 Regulation of Hippo signalling by p38 signalling. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Intracellular signal transduction, inherited across the MAP kinase family. Reason: Correct though general; the specific child p38MAPK cascade is also annotated. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0035556 intracellular signal transduction | IDA PMID:10838079 Distinct carboxy-termini confer divergent characteristics to... | ACCEPT | Summary: Characterisation of p38alpha and its splice isoform Mxi2 in stress- and mitogen-activated signalling. Reason: Correct though general; p38MAPK cascade (GO:0038066) is the more specific description. Supporting Evidence: PMID:10838079 Mxi2 is distinctively activated by stress stimuli and potently activated by mitogens. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IMP PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | KEEP AS NON CORE | Summary: VEGF signalling in HUVEC studied with p38alpha siRNA/SB203580; p38 mediates part of VEGF-induced HSP27 phosphorylation but not Ser82 or chemotaxis. Reason: Curators with full text annotated a p38alpha contribution to VEGF responses; the abstract shows it is limited (HSP27 Ser82 and migration are p38-independent). Non-core. Supporting Evidence: PMID:18440775 whereas HSP27 phosphorylation induced by H2O2 and TNFalpha was completely blocked by the p38 kinase inhibitor, SB203580, VEGF-stimulated serine 82 phosphorylation was resistant to SB203580 and small interfering(si)RNA-mediated knockdown of p38 kinase and MAPKAPK2 Reactome:R-HSA-5218804 In primary cultured human umbilical vein endothelial cells (HUVECs) VEGF-induced activation of SAPK2/p38MAPK |
| GO:0038066 p38MAPK cascade | IDA PMID:10330143 Targeting of p38 mitogen-activated protein kinases to MEF2 t... | ACCEPT | Summary: p38alpha phosphorylates MEF2 transcription factors downstream of MKK6 activation. Reason: MAPK14 is the prototypic MAPK tier of the p38MAPK cascade; this is its core biological process. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 |
| GO:0038066 p38MAPK cascade | IEA GO_REF:0000002 | ACCEPT | Summary: p38MAPK cascade inferred from the MAPK14 InterPro family signature. Reason: MAPK14 is the prototypic MAPK tier of the p38MAPK cascade; this is its core biological process. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0038066 p38MAPK cascade | ISS GO_REF:0000024 | ACCEPT | Summary: p38MAPK cascade by similarity to mouse p38alpha. Reason: MAPK14 is the prototypic MAPK tier of the p38MAPK cascade; this is its core biological process. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6 file:human/MAPK14/MAPK14-uniprot.txt Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. |
| GO:0038066 p38MAPK cascade | TAS Reactome:R-HSA-450302 | ACCEPT | Summary: Reactome: activated TAK1 acts via MKK3/4/6 to activate p38 MAPK. Reason: MAPK14 is the prototypic MAPK tier of the p38MAPK cascade; this is its core biological process. Supporting Evidence: Reactome:R-HSA-450302 Once p38 MAPK is phosphorylated it activates numerous downstream substrates |
| GO:0042770 signal transduction in response to DNA damage | IMP PMID:20160708 Feedback between p21 and reactive oxygen production is neces... | KEEP AS NON CORE | Summary: MAPK14 acts in the delayed DDR signalling chain (GADD45-MAPK14-GRB2-TGFBR2-TGFbeta) that sustains DNA damage foci. Reason: p38 participates in DNA-damage signalling (also MK2-dependent checkpoint maintenance); valid, non-core. Supporting Evidence: PMID:20160708 These data show that ROS production, mediated by a delayed signalling through MAPK14, contributes to DDR by constant replenishment of short-lived DNA damage foci. PMID:20932473 However, we did observe strong direct phosphorylation of TIAR by p38 in vitro |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IMP NOT PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: NOT annotation: siRNA against p38alpha had no effect on VEGF-induced endothelial chemotaxis. Reason: The negative result is explicitly stated in the abstract and the NOT qualifier is appropriate. Supporting Evidence: PMID:18440775 whereas inhibition of the p38 kinase pathway using either SB203580 or siRNAs against p38alpha or MAPKAPK2, had no significant effect on the chemotactic response to VEGF |
| GO:0045648 positive regulation of erythrocyte differentiation | IMP PMID:23483889 Protein arginine methyltransferase 1 interacts with and acti... | KEEP AS NON CORE | Summary: p38alpha (not p38beta) knockdown reduces araC/PRMT1-induced erythroid differentiation of K562 and CD34+ cells. Reason: Isoform-specific knockdown evidence; consistent with the role of p38alpha in stress erythropoiesis; downstream developmental outcome. Supporting Evidence: PMID:23483889 Knockdown of p38Ξ± resulted in dramatically reduced erythroid differentiation induced by araC, while knockdown of p38Ξ² had no effect file:human/MAPK14/MAPK14-uniprot.txt Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression |
| GO:0045663 positive regulation of myoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of myoblast differentiation by similarity to mouse p38alpha (P47811). Reason: Mouse p38alpha is required for myoblast differentiation/fusion via MEF2 and chromatin regulation; transfer to human is reasonable but this is a downstream developmental role. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 Reactome:R-HSA-448958 Activated p38 MAPK may translocate into the nucleus to further activate myogenic related transcription factors. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | KEEP AS NON CORE | Summary: VEGF signalling in HUVEC studied with p38alpha siRNA/SB203580; p38 mediates part of VEGF-induced HSP27 phosphorylation but not Ser82 or chemotaxis. Reason: Curators with full text annotated a p38alpha contribution to VEGF responses; the abstract shows it is limited (HSP27 Ser82 and migration are p38-independent). Non-core. Supporting Evidence: PMID:18440775 whereas HSP27 phosphorylation induced by H2O2 and TNFalpha was completely blocked by the p38 kinase inhibitor, SB203580, VEGF-stimulated serine 82 phosphorylation was resistant to SB203580 and small interfering(si)RNA-mediated knockdown of p38 kinase and MAPKAPK2 Reactome:R-HSA-5218804 In primary cultured human umbilical vein endothelial cells (HUVECs) VEGF-induced activation of SAPK2/p38MAPK |
| GO:0048273 mitogen-activated protein kinase p38 binding | IPI PMID:11035004 C-terminal elements control location, activation threshold, ... | MODIFY | Summary: RSKB/MSK2 docks onto p38alpha via C-terminal elements; the annotation places 'MAPK p38 binding' on MAPK14 itself. Reason: 'mitogen-activated protein kinase p38 binding' describes the partner's (RSKB) function; from the MAPK14 side the informative MF is binding to a protein kinase substrate. Proposed replacements: protein kinase binding Supporting Evidence: PMID:11035004 These findings support that the RSKB C-terminal extension contains elements that control activation threshold, subcellular location, and p38 docking. file:human/MAPK14/MAPK14-uniprot.txt RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3 |
| GO:0051149 positive regulation of muscle cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of muscle cell differentiation inferred by ARBA. Reason: Consistent with the p38alpha-MEF2 axis in myogenesis; non-core. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 |
| GO:0051149 positive regulation of muscle cell differentiation | TAS Reactome:R-HSA-525793 | KEEP AS NON CORE | Summary: Reactome Myogenesis: CDO/BOC co-receptors activate p38, which activates myogenic transcription factors. Reason: p38alpha promotes myogenic differentiation via MEF2 phosphorylation; well supported but downstream/pleiotropic. Supporting Evidence: Reactome:R-HSA-525793 CDO modulates the Cdc42 and p38 mitogen-activated protein kinase (MAPK) pathways PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 |
| GO:0051403 stress-activated MAPK cascade | IDA PMID:35857590 ZAKΞ±-driven ribotoxic stress response activates the human NL... | ACCEPT | Summary: UVB/ribotoxic stress activates ZAKalpha-p38 signalling in keratinocytes. Reason: p38alpha is a stress-activated MAPK; this is a core process annotation. Supporting Evidence: PMID:35857590 UVB induced bona fide RSR activation in N/TERT keratinocytes marked by ZAKΞ±, p38 and JNK phosphorylation at earlier time points |
| GO:0051403 stress-activated MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: Stress-activated MAPK cascade inferred by ARBA. Reason: p38alpha is a stress-activated MAPK; this is a core process annotation. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. |
| GO:0051403 stress-activated MAPK cascade | IMP PMID:7535770 Pro-inflammatory cytokines and environmental stress cause p3... | ACCEPT | Summary: p38 is activated by environmental stress and cytokines via dual Thr180/Tyr182 phosphorylation; mutation of these sites blocks activation. Reason: p38alpha is a stress-activated MAPK; this is a core process annotation. Supporting Evidence: PMID:7535770 Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. PMID:7535770 The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. |
| GO:0051525 NFAT protein binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: NFAT protein binding by similarity to mouse p38alpha. Reason: p38 phosphorylates NFAT family members; binding to an NFAT substrate is plausible but secondary to kinase activity (the substrate relationship is better captured as has_input). Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | TAS PMID:20932473 DNA damage activates a spatially distinct late cytoplasmic c... | KEEP AS NON CORE | Summary: p38 phosphorylates TIAR (and activates MK2), stabilising Gadd45alpha mRNA through its 3'-UTR after DNA damage. Reason: Supported by direct phosphorylation of TIAR; a context-specific post-transcriptional output of p38/MK2 signalling. Supporting Evidence: PMID:20932473 However, we did observe strong direct phosphorylation of TIAR by p38 in vitro PMID:20932473 We show that p38/MK2-dependent phosphorylation of three key targets involved in RNA regulation, hnRNPA0, TIAR, and PARN, stabilizes an ortherwise unstable Gadd45Ξ± transcript through its 3'-UTR. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | KEEP AS NON CORE | Summary: SASH1 scaffolds TLR4 signalling and promotes LPS-induced p38 activation in endothelial cells (MGI curation). Reason: p38alpha is a classic LPS/TLR4-activated kinase; the acts_upstream_of_or_within qualifier appropriately reflects that p38 activation is a readout here. Supporting Evidence: PMID:23776175 This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-ΞΊB, JNK, and p38 activation PMID:7535770 Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. |
| GO:0071223 cellular response to lipoteichoic acid | IMP PMID:26649771 Expression of Beta-Defensin 131 Promotes an Innate Immune Re... | MARK AS OVER ANNOTATED | Summary: LTA-induced DEFB131 expression in prostate epithelial cells depends on TLR2 and p38 (SB203580). Reason: Single-context inhibitor study; SB203580 does not distinguish p38alpha from p38beta and the endpoint is a downstream gene-expression change. Supporting Evidence: PMID:26649771 We found that DEFB131 expression was induced by LTA stimulation through TLR2 and p38MAPK/NF-ΞΊB activation file:human/MAPK14/MAPK14-deep-research-falcon.md Claims should be considered MAPK14 specific only when supported by isoform-selective genetics, validated selective inhibitors, or direct biochemical assays. |
| GO:0071479 cellular response to ionizing radiation | IMP PMID:20160708 Feedback between p21 and reactive oxygen production is neces... | KEEP AS NON CORE | Summary: Following ionizing radiation, suppression of MAPK14 signalling reduces ROS and DNA damage foci. Reason: Stress response context of p38 signalling. Supporting Evidence: PMID:20160708 Suppression of MAPK14 signalling or antioxidant treatment at day 6 after IR reduced ROS levels by about half |
| GO:0071493 cellular response to UV-B | IDA PMID:35857590 ZAKΞ±-driven ribotoxic stress response activates the human NL... | KEEP AS NON CORE | Summary: p38alpha acts downstream of ZAKalpha in the UVB-induced ribotoxic stress response and phosphorylates NLRP1. Reason: Well supported stress-response context of p38alpha; non-core relative to MAP kinase activity/p38MAPK cascade. Supporting Evidence: PMID:35857590 UVB induced bona fide RSR activation in N/TERT keratinocytes marked by ZAKΞ±, p38 and JNK phosphorylation at earlier time points file:human/MAPK14/MAPK14-uniprot.txt Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis |
| GO:0071493 cellular response to UV-B | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular response to UV-B inferred by ARBA. Reason: Well supported stress-response context of p38alpha; non-core relative to MAP kinase activity/p38MAPK cascade. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis |
| GO:0090398 cellular senescence | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular senescence inferred by ARBA. Reason: Consistent with experimental data implicating MAPK14 in the p21-ROS senescence loop. Supporting Evidence: PMID:20160708 The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. |
| GO:0090398 cellular senescence | TAS Reactome:R-HSA-2559583 | KEEP AS NON CORE | Summary: Reactome oxidative stress induced senescence includes p38 MAPK signalling. Reason: p38alpha contributes to establishing senescence (MK5/PRAK-p53, ROS feedback loop); a downstream outcome. Supporting Evidence: Reactome:R-HSA-2559583 Oxidative stress, which may or may not be caused by oncogenic RAS signaling, can also trigger senescence. PMID:20160708 The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. |
| GO:0090400 stress-induced premature senescence | IMP PMID:20160708 Feedback between p21 and reactive oxygen production is neces... | KEEP AS NON CORE | Summary: MAPK14 signalling is required for the ROS feedback loop that stabilises irradiation-induced (stress-induced premature) senescence. Reason: Supported by MAPK14 inhibition/knockdown data; a downstream outcome. Supporting Evidence: PMID:20160708 The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. PMID:20160708 These data show that ROS production, mediated by a delayed signalling through MAPK14, contributes to DDR by constant replenishment of short-lived DNA damage foci. |
| GO:0098586 cellular response to virus | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Cellular response to virus inferred by ARBA. Reason: p38 activation is a generic stress/innate response; a single inhibitor-based study of Gal-9 induction does not make 'cellular response to virus' an informative MAPK14 annotation. Supporting Evidence: PMID:25754930 Blocking p38, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase (ERK), inhibited DV-induced expression of Gal-9. file:human/MAPK14/MAPK14-deep-research-falcon.md Claims should be considered MAPK14 specific only when supported by isoform-selective genetics, validated selective inhibitors, or direct biochemical assays. |
| GO:0098586 cellular response to virus | IMP PMID:25754930 Up-regulation of galectin-9 induces cell migration in human ... | MARK AS OVER ANNOTATED | Summary: Dengue virus-induced galectin-9 expression in dendritic cells requires p38 (inhibitor study). Reason: p38 activation is a generic stress/innate response; a single inhibitor-based study of Gal-9 induction does not make 'cellular response to virus' an informative MAPK14 annotation. Supporting Evidence: PMID:25754930 Blocking p38, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase (ERK), inhibited DV-induced expression of Gal-9. file:human/MAPK14/MAPK14-deep-research-falcon.md Claims should be considered MAPK14 specific only when supported by isoform-selective genetics, validated selective inhibitors, or direct biochemical assays. |
| GO:0106310 protein serine kinase activity | EXP PMID:11010976 Differential activation of p38 mitogen-activated protein kin... | ACCEPT | Summary: In vitro kinase assays with MKK6-activated p38alpha (serine phosphorylation reaction curated by UniProt/Rhea). Reason: Experimentally supported; MAPK14 phosphorylates serine (and threonine) residues. GO:0004707 remains the core MF. Supporting Evidence: PMID:11010976 found that some MKK6 mutants can efficiently activate p38alpha but not p38gamma file:human/MAPK14/MAPK14-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:0106310 protein serine kinase activity | EXP PMID:35857590 ZAKΞ±-driven ribotoxic stress response activates the human NL... | ACCEPT | Summary: p38alpha phosphorylates serine residues in the NLRP1 disordered linker in vitro. Reason: Experimentally supported; MAPK14 phosphorylates serine (and threonine) residues. GO:0004707 remains the core MF. Supporting Evidence: PMID:35857590 Both p38Ξ± and p38Ξ² could phosphorylate recombinant NLRP1DR, including residues within the ZAKΞ± motifs file:human/MAPK14/MAPK14-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine kinase activity inferred from the Rhea serine-phosphorylation reaction (RHEA:17989). Reason: Correct but incomplete: MAPK14 phosphorylates both Ser and Thr; MAP kinase activity (GO:0004707) is the preferred, more specific description. Supporting Evidence: file:human/MAPK14/MAPK14-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:1900015 regulation of cytokine production involved in inflammatory response | IDA PMID:15251176 An inhibitor of p38 MAP kinase downregulates cytokine releas... | KEEP AS NON CORE | Summary: The p38 inhibitor SB203580 reduces sulfur-mustard-induced IL-8, IL-6, TNF-alpha and IL-1beta release from keratinocytes. Reason: p38alpha (CSBP) is a well-established regulator of inflammatory cytokine production; supported here only by inhibitor data, so non-core. Supporting Evidence: PMID:15251176 These results show that p38 MAP kinase plays a role in SM-induced cytokine production in HEK PMID:7997261 Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production |
| GO:1901741 positive regulation of myoblast fusion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of myoblast fusion by similarity to mouse p38alpha (P47811). Reason: Mouse p38alpha is required for myoblast differentiation/fusion via MEF2 and chromatin regulation; transfer to human is reasonable but this is a downstream developmental role. Supporting Evidence: PMID:10330143 the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2 Reactome:R-HSA-448958 Activated p38 MAPK may translocate into the nucleus to further activate myogenic related transcription factors. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Reactome neutrophil degranulation proteomics lists MAPK14 among proteins in granule lumen/extracellular release. Reason: MAPK14 is a soluble cytosolic/nuclear kinase with no signal peptide; detection in granule/secretome proteomics does not establish a functional extracellular or granule-lumen location. Same treatment as the MAPK1 review. Supporting Evidence: Reactome:R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins file:human/MAPK14/MAPK14-deep-research-falcon.md MAPK14 is a soluble intracellular kinase operating in both |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | IMP PMID:20160708 Feedback between p21 and reactive oxygen production is neces... | KEEP AS NON CORE | Summary: MAPK14 signalling is required for mitochondrial ROS production in the senescence feedback loop. Reason: Supported by MAPK14 inhibition in this study; an indirect, downstream effect. Supporting Evidence: PMID:20160708 Suppression of MAPK14 signalling or antioxidant treatment at day 6 after IR reduced ROS levels by about half PMID:20160708 These data show that ROS production, mediated by a delayed signalling through MAPK14, contributes to DDR by constant replenishment of short-lived DNA damage foci. |
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Download this section (compressed HTML)Q: Many process annotations (IL-12 production, response to virus, cyclase activity, response to LTA) rest on SB203580/SB202190 inhibitor data that do not distinguish p38 alpha from p38 beta; should these be re-evaluated against isoform-selective genetic evidence (MAPK14 vs MAPK11 knockdown/knockout)?
Q: Should the numerous p38 alpha substrates currently represented as protein-binding rows (MK2, MK3, MSK1/2, MNK1/2, Rb, p18Hamlet/ZNHIT1) be captured instead as has_input on MAP kinase activity in a p38 cascade GO-CAM?
Q: Does the Mxi2 splice isoform (Q16539-3), which binds ERK1/2 and nucleoporins and promotes ERK nuclear import, warrant isoform-specific annotations distinct from the canonical kinase?
Experiment: Analog-sensitive MAPK14 allele (with MAPK11 knockout background) combined with thiophosphate labelling and quantitative phosphoproteomics after anisomycin or LPS stimulation to define direct p38 alpha substrates and separate them from MK2/MSK-dependent phosphosites.
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