TYPE ONE PROTEIN PHOSPHATASE 4 (TOPP4) is a PP1-family serine/threonine protein phosphatase whose regulatory partners and substrates connect it to several developmental and stress responses. TOPP4 dephosphorylates DELLA proteins RGA and GAI in gibberellin signaling, PIF5 during red-light responses, PIN1 in pavement-cell polarity and trafficking, and ATG13a during carbon-starvation-induced autophagy. It has nuclear, cytoplasmic and plasma-membrane-associated pools. TOPP4 also associates with APRF1 and LD in a transcription-termination-linked module involved in FLC chromatin repression, although that module's direct phosphatase substrate has not been established. Substrate dephosphorylation has different consequences in different pathways: it promotes DELLA turnover but stabilizes PIF5.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000164 protein phosphatase type 1 complex | ISS PMID:7678768 Expression of multiple type 1 phosphoprotein phosphatases in... | ACCEPT | Summary: TOPP4 is a catalytic subunit of PP1-type complexes. Reason: PMID:7678768 identifies TOPP4 among five Arabidopsis PP1 catalytic isoforms. Full PMID:19329567 then tests all nine Arabidopsis TOPP isoforms with AtInh3 and reports recombinant GST-TOPP4 coprecipitation with FLAG-tagged Inh3, with GST alone as a negative control and RVxF disruption abolishing binding. This supports TOPP4 as the catalytic component of a regulated PP1 complex. The native-plant coimmunoprecipitation in that paper detects PP1c collectively and is not represented as TOPP4-isoform-specific. AtInh3 (AT2G31305) is distinct from the separate PP1R3 regulator considered in PMID:32948668. Supporting Evidence: PMID:19329567 FLAG-tagged Inh3 (FLAG:VfInh3 and FLAG:AtInh3) was coprecipitated with glutathione S -transferase (GST)-tagged-PP1c (GST-VfPP1c-1 and GST-TOPP4) but not with GST alone ( Fig. 2, D and E ). PMID:7678768 five distinct Arabidopsis cDNA clones (TOPP1, TOPP2, TOPP3, TOPP4 and TOPP5) which encode the catalytic subunit (PP1c) of type 1 protein phosphatases. |
| GO:0004722 protein serine/threonine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: TOPP4 has experimentally supported serine/threonine protein phosphatase activity. Reason: The conserved PP1 activity is corroborated by purified target phosphatase assays and direct substrate dephosphorylation. PMID:21222654 tests plant PP1 isoforms with inhibitor-2; independent TOPP4 RGA/GAI and ATG13a experiments establish the same activity. The IBA therefore remains a sound conserved-function assertion rather than a weak donor-count transfer. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:21222654 Identification and characterization of AtI-2, an Arabidopsis... | ACCEPT | Summary: TOPP4 has experimentally supported serine/threonine protein phosphatase activity. Reason: The conserved PP1 activity is corroborated by purified target phosphatase assays and direct substrate dephosphorylation. PMID:21222654 tests plant PP1 isoforms with inhibitor-2; independent TOPP4 RGA/GAI and ATG13a experiments establish the same activity. The IBA therefore remains a sound conserved-function assertion rather than a weak donor-count transfer. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:25010794 Arabidopsis DELLA protein degradation is controlled by a typ... | ACCEPT | Summary: TOPP4 has experimentally supported serine/threonine protein phosphatase activity. Reason: The conserved PP1 activity is corroborated by purified target phosphatase assays and direct substrate dephosphorylation. PMID:21222654 tests plant PP1 isoforms with inhibitor-2; independent TOPP4 RGA/GAI and ATG13a experiments establish the same activity. The IBA therefore remains a sound conserved-function assertion rather than a weak donor-count transfer. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: TOPP4 has experimentally supported serine/threonine protein phosphatase activity. Reason: The conserved PP1 activity is corroborated by purified target phosphatase assays and direct substrate dephosphorylation. PMID:21222654 tests plant PP1 isoforms with inhibitor-2; independent TOPP4 RGA/GAI and ATG13a experiments establish the same activity. The IBA therefore remains a sound conserved-function assertion rather than a weak donor-count transfer. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0005515 protein binding | IPI PMID:25010794 Arabidopsis DELLA protein degradation is controlled by a typ... | MODIFY | Summary: DELLA interaction is part of a demonstrated TOPP4 substrate-dephosphorylation reaction. Reason: The original RGA/GAI binding experiment is mechanistically resolved in the same study by direct TOPP4 dephosphorylation. Replace bare protein binding with the experimentally established protein serine/threonine phosphatase activity already present in this review; this preserves the functional meaning of the interaction without claiming that DELLA proteins are DNA-binding transcription factors. Proposed replacements: protein serine/threonine phosphatase activity Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI |
| GO:0005515 protein binding | IPI PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | MODIFY | Summary: TOPP4 interacts with a PIF transcription factor. Reason: The original supporting entity AT1G09530 is PIF3, a DNA-binding transcription factor assayed in the PIF interaction study. DNA-binding transcription factor binding is a more informative description of this association. The demonstrated PIF5 dephosphorylation mechanism is not automatically assigned to PIF3. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | MODIFY | Summary: PIF5 interaction participates in direct substrate dephosphorylation. Reason: The source AT3G59060 is PIF5. Its direct TOPP4 binding and dephosphorylation establish an informative phosphatase activity; the replacement is already independently represented. This is distinct from extrapolating the PIF5 substrate reaction to every PIF interactor. Proposed replacements: protein serine/threonine phosphatase activity Supporting Evidence: PMID:26704640 TOPP4 interacts directly with PIF5 and dephosphorylates it. |
| GO:0005515 protein binding | IPI PMID:32948668 Role of Protein Phosphatase1 Regulatory Subunit3 in Mediatin... | REMOVE | Summary: PP1R3 binding supports regulation of TOPP4 but bare protein binding is uninformative. Reason: PMID:32948668 explicitly reports PP1R3 interaction, inhibition of TOPP enzyme activity and facilitation of TOPP4 nuclear localization. Preserve these mechanisms in the evidence narrative, but do not invent a specific catalytic or binding function from generic association alone. Removal is the project GO:0005515 policy, not rejection of the measured complex. |
| GO:0005515 protein binding | IPI PMID:35961047 Type one protein phosphatase regulates fixed-carbon starvati... | MODIFY | Summary: ATG13 binding includes a demonstrated TOPP4 substrate-dephosphorylation reaction. Reason: Full PMID:35961047 directly tests TOPP4-GST dephosphorylation of ATG13a, with phosphatase-inhibitor controls. Replace bare binding by the established serine/threonine phosphatase activity. ATG13b interaction is starvation-dependent in co-IP; the target-specific ATG13a catalytic assay is not automatically extended to every binding partner. Proposed replacements: protein serine/threonine phosphatase activity Supporting Evidence: PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0005634 nucleus | EXP PMID:19329567 Identification and functional characterization of inhibitor-... | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005634 nucleus | EXP PMID:25010794 Arabidopsis DELLA protein degradation is controlled by a typ... | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005634 nucleus | EXP PMID:25560878 TYPE-ONE PROTEIN PHOSPHATASE4 regulates pavement cell interd... | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005634 nucleus | IDA PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: TOPP4 has an experimentally demonstrated nuclear pool. Reason: Target TOPP4-GFP localization in PMID:25010794/25560878 and native-promoter confirmation support the nucleus. The source-specific AtInh3 and PIF studies are corroborative; nuclear localization is not inferred solely from another PP1 isoform or imposed as exclusive. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:19329567 Identification and functional characterization of inhibitor-... | ACCEPT | Summary: TOPP4 also localizes to the cytoplasm. Reason: Full PMID:25560878 explicitly identifies a cytoplasmic TOPP4 pool and confirms the distribution with its native promoter. This independently supports the conserved and electronic annotations as well as the experimental source rows; the nuclear termination-associated function does not negate the cytoplasmic pool. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:25560878 TYPE-ONE PROTEIN PHOSPHATASE4 regulates pavement cell interd... | ACCEPT | Summary: TOPP4 also localizes to the cytoplasm. Reason: Full PMID:25560878 explicitly identifies a cytoplasmic TOPP4 pool and confirms the distribution with its native promoter. This independently supports the conserved and electronic annotations as well as the experimental source rows; the nuclear termination-associated function does not negate the cytoplasmic pool. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: TOPP4 also localizes to the cytoplasm. Reason: Full PMID:25560878 explicitly identifies a cytoplasmic TOPP4 pool and confirms the distribution with its native promoter. This independently supports the conserved and electronic annotations as well as the experimental source rows; the nuclear termination-associated function does not negate the cytoplasmic pool. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: TOPP4 also localizes to the cytoplasm. Reason: Full PMID:25560878 explicitly identifies a cytoplasmic TOPP4 pool and confirms the distribution with its native promoter. This independently supports the conserved and electronic annotations as well as the experimental source rows; the nuclear termination-associated function does not negate the cytoplasmic pool. Supporting Evidence: PMID:25560878 TOPP4 protein was mainly localized to the nucleus and plasma membrane, and some TOPP4 proteins were found in the cytoplasm |
| GO:0006468 protein phosphorylation | IPI PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | MODIFY | Summary: TOPP4 removes phosphate from PIF5 rather than catalyzing phosphate addition. Reason: The original PMID:26704640 phosphorylation study explicitly establishes direct PIF5 dephosphorylation by TOPP4 and consequent inhibition of PIF5 degradation. The role-specific process is protein dephosphorylation, already present elsewhere in this review. This correction concerns the measured chemical step, not a claim that a phosphatase can never regulate a broader phosphorylation pathway. Proposed replacements: protein dephosphorylation Supporting Evidence: PMID:26704640 TOPP4 interacts directly with PIF5 and dephosphorylates it. |
| GO:0006470 protein dephosphorylation | TAS PMID:7678768 Expression of multiple type 1 phosphoprotein phosphatases in... | ACCEPT | Summary: TOPP4 directly participates in protein dephosphorylation. Reason: The original catalytic-isoform characterization is corroborated by target RGA/GAI, PIF5, PIN1 and ATG13a substrate assays. TOPP4 performs the chemical step rather than merely responding to the pathway. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI PMID:35961047 TOPP4, like λPP ( Supplemental Figure S12B ), directly dephosphorylates ATG13a in vitro |
| GO:0009740 gibberellic acid mediated signaling pathway | IGI PMID:25010794 Arabidopsis DELLA protein degradation is controlled by a typ... | ACCEPT | Summary: TOPP4 directly contributes to gibberellin signaling through DELLA dephosphorylation. Reason: Native genetic interactions and target substrate experiments in PMID:25010794 connect TOPP4-mediated RGA/GAI dephosphorylation with their stability and GA signaling. This is a substrate-level signaling function, not merely a pleiotropic dwarf phenotype. Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI |
| GO:0010161 red light signaling pathway | IGI PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | ACCEPT | Summary: TOPP4 participates in red-light signaling through PIF5 regulation. Reason: PMID:26704640 combines red-light-dependent genetic phenotypes with direct PIF5 interaction/dephosphorylation and altered degradation. TOPP4 stabilizes PIF5 and attenuates photomorphogenesis in the tested seedling context, a mechanistic contribution distinct from its DELLA-turnover effect. Supporting Evidence: PMID:26704640 TOPP4 interacts directly with PIF5 and dephosphorylates it. |
| GO:0010161 red light signaling pathway | IMP PMID:26704640 TOPP4 Regulates the Stability of PHYTOCHROME INTERACTING FAC... | ACCEPT | Summary: TOPP4 participates in red-light signaling through PIF5 regulation. Reason: PMID:26704640 combines red-light-dependent genetic phenotypes with direct PIF5 interaction/dephosphorylation and altered degradation. TOPP4 stabilizes PIF5 and attenuates photomorphogenesis in the tested seedling context, a mechanistic contribution distinct from its DELLA-turnover effect. Supporting Evidence: PMID:26704640 TOPP4 interacts directly with PIF5 and dephosphorylates it. |
| GO:0016311 dephosphorylation | IDA PMID:25010794 Arabidopsis DELLA protein degradation is controlled by a typ... | MODIFY | Summary: The demonstrated dephosphorylation substrate is protein. Reason: PMID:25010794 directly assays the DELLA proteins RGA and GAI. Refine the general dephosphorylation process to protein dephosphorylation, which is already independently supported in this review. Proposed replacements: protein dephosphorylation Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad hydrolase activity is protein serine/threonine phosphatase activity. Reason: TOPP4 is a PP1 catalytic subunit with target-specific phosphoprotein dephosphorylation assays. The experimentally established phosphatase term is more informative than the broad InterPro-derived hydrolase term and is already represented. Proposed replacements: protein serine/threonine phosphatase activity Supporting Evidence: PMID:25010794 TOPP4 is able to directly bind and dephosphorylate RGA and GAI |
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Q: How do regulatory partners direct TOPP4 toward substrates whose dephosphorylation either stabilizes or destabilizes the target protein?
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