PPP3CA encodes calcineurin catalytic subunit A alpha, a calcium/calmodulin-activated serine/threonine phosphatase (EC 3.1.3.16) that functions in the calcineurin holoenzyme to dephosphorylate signaling substrates including NFAT-family transcription factors. Its core roles are phosphoprotein dephosphorylation and calcineurin-NFAT pathway signaling, with additional context-dependent functions in neuronal, immune, muscle, and renal physiology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization is consistent with established PPP3CA signaling biology [PMID:19154138, PMID:22343722]. Reason: PPP3CA acts on cytoplasmic signaling substrates and scaffolded signaling complexes. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005955 calcineurin complex | IBA GO_REF:0000033 | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. Supporting Evidence: file:human/PPP3CA/PPP3CA-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005516 calmodulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0033173 calcineurin-NFAT signaling cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PPP3CA is a protein serine/threonine phosphatase catalytic subunit [PMID:19154138, PMID:30718414]. Reason: This is a core molecular-function annotation directly matching the known enzyme class. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is consistent with established PPP3CA signaling biology [PMID:19154138, PMID:22343722]. Reason: PPP3CA acts on cytoplasmic signaling substrates and scaffolded signaling complexes. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: PPP3CA can be recruited to the plasma membrane by scaffolds such as AKAP79 [PMID:22343722]. Reason: Membrane recruitment is experimentally supported but is context-dependent rather than the universal core state. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: Hydrolase activity is correct but overly broad for PPP3CA. Reason: A more specific phosphatase term better represents known catalytic chemistry for calcineurin A alpha. Proposed replacements: protein serine/threonine phosphatase activity calmodulin-dependent protein phosphatase activity |
| GO:0030018 Z disc | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Z-disc association is described in muscle-context interaction studies [PMID:11114196, PMID:11842093]. Reason: Contextual localization in muscle; not a universal core location. |
| GO:0033173 calcineurin-NFAT signaling cascade | IEA GO_REF:0000117 | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0042383 sarcolemma | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Sarcolemma localization is supported in muscle-related contexts [PMID:15955804]. Reason: Context-specific localization; not the most general core compartment term. |
| GO:0043197 dendritic spine | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dendritic-spine localization is plausible in neuronal signaling contexts [PMID:22343722]. Reason: Supported in specific cellular contexts but not a universal core localization. |
| GO:0097720 calcineurin-mediated signaling | IEA GO_REF:0000002 | ACCEPT | Summary: Calcineurin-mediated signaling is a direct and central biological-process role of PPP3CA. Reason: This is a core pathway-level annotation aligned with extensive calcineurin literature. |
| GO:0005515 protein binding | IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:19896943 WITHDRAWN: USP14 stabilizes calcineurin and regulates NFAT/A... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:24418105 Direct association of the unique C-terminal tail of transmem... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:8524402 Crystal structures of human calcineurin and the human FKBP12... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005829 cytosol | NAS PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | NAS PMID:28126489 The protein serine/threonine phosphatases PP2A, PP1 and calc... | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0070886 positive regulation of calcineurin-NFAT signaling cascade | NAS PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | ACCEPT | Summary: PPP3CA activity supports NFAT activation and therefore positive regulation of calcineurin-NFAT signaling [PMID:22343722, PMID:8631904]. Reason: Term is consistent with known pathway directionality for calcineurin catalytic function. |
| GO:0070886 positive regulation of calcineurin-NFAT signaling cascade | NAS PMID:8631904 Calcineurin binds the transcription factor NFAT1 and reversi... | ACCEPT | Summary: PPP3CA activity supports NFAT activation and therefore positive regulation of calcineurin-NFAT signaling [PMID:22343722, PMID:8631904]. Reason: Term is consistent with known pathway directionality for calcineurin catalytic function. |
| GO:1905665 positive regulation of calcium ion import across plasma membrane | NAS PMID:17640527 AKAP79/150 anchoring of calcineurin controls neuronal L-type... | MARK AS OVER ANNOTATED | Summary: Directional regulation of calcium import is highly context-dependent and potentially conflicting across systems. Reason: Process-level directionality is not robust as a core PPP3CA annotation. |
| GO:1905949 negative regulation of calcium ion import across plasma membrane | NAS PMID:17640527 AKAP79/150 anchoring of calcineurin controls neuronal L-type... | MARK AS OVER ANNOTATED | Summary: Directional regulation of calcium import is highly context-dependent and potentially conflicting across systems. Reason: Process-level directionality is not robust as a core PPP3CA annotation. |
| GO:0004722 protein serine/threonine phosphatase activity | IMP PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu... | ACCEPT | Summary: PPP3CA is a protein serine/threonine phosphatase catalytic subunit [PMID:19154138, PMID:30718414]. Reason: This is a core molecular-function annotation directly matching the known enzyme class. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:1903235 positive regulation of calcium ion-dependent exocytosis of neurotransmitter | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal exocytosis-regulation linkage is plausible in synaptic calcineurin signaling. Reason: Likely context-dependent downstream physiology rather than universally core. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IDA PMID:30718414 Calcineurin dephosphorylates Kelch-like 3, reversing phospho... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0110062 negative regulation of angiotensin-activated signaling pathway | IDA PMID:30718414 Calcineurin dephosphorylates Kelch-like 3, reversing phospho... | KEEP AS NON CORE | Summary: Supported kidney signaling context where calcineurin opposes angiotensin-driven phosphorylation events [PMID:30718414]. Reason: Evidence is strong but process scope is context-specific rather than core pan-context function. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:30718414 Calcineurin dephosphorylates Kelch-like 3, reversing phospho... | ACCEPT | Summary: PPP3CA is a protein serine/threonine phosphatase catalytic subunit [PMID:19154138, PMID:30718414]. Reason: This is a core molecular-function annotation directly matching the known enzyme class. |
| GO:0005516 calmodulin binding | EXP PMID:18384083 The complex structure of calmodulin bound to a calcineurin p... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005516 calmodulin binding | IDA PMID:18384083 The complex structure of calmodulin bound to a calcineurin p... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005516 calmodulin binding | IPI PMID:18384083 The complex structure of calmodulin bound to a calcineurin p... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005516 calmodulin binding | EXP PMID:24191726 The distal helix in the regulatory domain of calcineurin is ... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005516 calmodulin binding | IPI PMID:24191726 The distal helix in the regulatory domain of calcineurin is ... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005516 calmodulin binding | EXP PMID:27187005 Calcineurin in a Crowded World. | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005515 protein binding | IPI PMID:34446558 SPATA33 localizes calcineurin to the mitochondria and regula... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0042104 positive regulation of activated T cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Calcineurin signaling contributes to activated T-cell proliferation, but this is a higher-level physiological context. Reason: Biologically plausible yet not the most direct core process label for PPP3CA. |
| GO:0023057 negative regulation of signaling | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Negative regulation of signaling is too broad as a standalone process attribution for PPP3CA. Reason: PPP3CA can both positively and negatively affect distinct pathways depending on substrate/context. |
| GO:0050804 modulation of chemical synaptic transmission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chemical synaptic transmission modulation is plausible in neuronal calcineurin signaling contexts. Reason: Kept as non-core because it is a broad downstream neurophysiology term. |
| GO:0008544 epidermis development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Epidermis-development links are mostly orthology/context-derived and represent peripheral biology for PPP3CA. Reason: Retained as non-core because evidence is not the strongest direct core-function signal for human PPP3CA. |
| GO:0030216 keratinocyte differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keratinocyte differentiation linkage is plausible but peripheral relative to core calcineurin signaling. Reason: Evidence is largely contextual/orthology-backed rather than primary core-function evidence. |
| GO:0005515 protein binding | IPI PMID:28881575 Overexpression of C16orf74 is involved in aggressive pancrea... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005886 plasma membrane | IDA PMID:28881575 Overexpression of C16orf74 is involved in aggressive pancrea... | KEEP AS NON CORE | Summary: PPP3CA can be recruited to the plasma membrane by scaffolds such as AKAP79 [PMID:22343722]. Reason: Membrane recruitment is experimentally supported but is context-dependent rather than the universal core state. |
| GO:0097205 renal filtration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Renal filtration linkage is consistent with kidney-context calcineurin roles. Reason: Kept as non-core because this is tissue-physiology-level rather than direct molecular process annotation. |
| GO:0046878 positive regulation of saliva secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Saliva-secretion annotation represents specialized tissue physiology rather than core function. Reason: Retained as non-core due restricted physiological context. |
| GO:0061006 regulation of cell proliferation involved in kidney morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kidney morphogenesis/cell proliferation links are plausible but represent specific developmental context. Reason: Retained as non-core due context specificity and indirectness. |
| GO:0090193 positive regulation of glomerulus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of glomerulus development is plausible from renal calcineurin biology. Reason: Non-core developmental physiology term for PPP3CA. |
| GO:0048741 skeletal muscle fiber development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Skeletal-muscle-fiber development effects are plausible but peripheral to core enzymatic function. Reason: Represents context-dependent developmental biology rather than central molecular role. |
| GO:0045672 positive regulation of osteoclast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Osteoclast differentiation via calcineurin-NFAT is plausible but context-specific. Reason: Not core across all major PPP3CA biological contexts. |
| GO:0045669 positive regulation of osteoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Osteoblast-differentiation effects are plausible calcineurin/NFAT downstream physiology. Reason: Kept as non-core due indirect/process-level specificity. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IMP PMID:30254215 Novel calcineurin A (PPP3CA) variant associated with epileps... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0033173 calcineurin-NFAT signaling cascade | IMP PMID:26248042 Calcineurin Undergoes a Conformational Switch Evoked via Pep... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0097720 calcineurin-mediated signaling | IMP PMID:11005320 Genetic conservation of the immunophilin-binding domains of ... | ACCEPT | Summary: Calcineurin-mediated signaling is a direct and central biological-process role of PPP3CA. Reason: This is a core pathway-level annotation aligned with extensive calcineurin literature. |
| GO:0042060 wound healing | TAS PMID:18846255 Calsarcin-2 deficiency increases exercise capacity in mice t... | KEEP AS NON CORE | Summary: Wound-healing links reflect downstream physiological contexts of calcineurin/NFAT signaling. Reason: Not a specific core process assignment for PPP3CA itself. |
| GO:0005737 cytoplasm | IDA PMID:15955804 The sarcolemmal calcium pump inhibits the calcineurin/nuclea... | ACCEPT | Summary: Cytoplasmic localization is consistent with established PPP3CA signaling biology [PMID:19154138, PMID:22343722]. Reason: PPP3CA acts on cytoplasmic signaling substrates and scaffolded signaling complexes. |
| GO:0005886 plasma membrane | IDA PMID:15955804 The sarcolemmal calcium pump inhibits the calcineurin/nuclea... | KEEP AS NON CORE | Summary: PPP3CA can be recruited to the plasma membrane by scaffolds such as AKAP79 [PMID:22343722]. Reason: Membrane recruitment is experimentally supported but is context-dependent rather than the universal core state. |
| GO:0019897 extrinsic component of plasma membrane | IC PMID:15955804 The sarcolemmal calcium pump inhibits the calcineurin/nuclea... | KEEP AS NON CORE | Summary: Extrinsic plasma-membrane association can occur via scaffolded complexes [PMID:22343722]. Reason: Valid in specific contexts, but not the principal localization state. |
| GO:0033173 calcineurin-NFAT signaling cascade | IMP PMID:15955804 The sarcolemmal calcium pump inhibits the calcineurin/nuclea... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0051117 ATPase binding | IPI PMID:15955804 The sarcolemmal calcium pump inhibits the calcineurin/nuclea... | KEEP AS NON CORE | Summary: ATPase binding is plausible from interaction studies but secondary to phosphatase catalytic function. Reason: Valid interaction-level annotation with limited functional specificity. |
| GO:0005515 protein binding | IPI PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0043403 skeletal muscle tissue regeneration | TAS PMID:18846255 Calsarcin-2 deficiency increases exercise capacity in mice t... | KEEP AS NON CORE | Summary: Skeletal-muscle regeneration links are plausible but reflect specialized physiological settings. Reason: Not a primary core process for broad PPP3CA function assignment. |
| GO:0045785 positive regulation of cell adhesion | IMP PMID:21785830 The effect of down regulation of calcineurin AΞ± by lentivira... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell adhesion appears mainly from disease/cell-line contexts. Reason: Likely over-extended from context-specific phenotypes rather than core PPP3CA role. |
| GO:0030335 positive regulation of cell migration | IMP PMID:21785830 The effect of down regulation of calcineurin AΞ± by lentivira... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell migration is supported mainly by cancer-context perturbation studies [PMID:20422345, PMID:21785830]. Reason: Likely context-specific/pleiotropic and not a robust core function term for PPP3CA. |
| GO:0030335 positive regulation of cell migration | IMP PMID:20422345 Calcineurin promotes proliferation, migration, and invasion ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell migration is supported mainly by cancer-context perturbation studies [PMID:20422345, PMID:21785830]. Reason: Likely context-specific/pleiotropic and not a robust core function term for PPP3CA. |
| GO:0005515 protein binding | IPI PMID:18218901 NFAT binding and regulation of T cell activation by the cyto... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:12809556 Phosphorylation of calcipressin 1 increases its ability to i... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:12218175 Crystal structure of calcineurin-cyclophilin-cyclosporin sho... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:26248042 Calcineurin Undergoes a Conformational Switch Evoked via Pep... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:27974827 Investigating the human Calcineurin Interaction Network usin... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005516 calmodulin binding | IDA PMID:19404396 Domain swapping and different oligomeric States for the comp... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005737 cytoplasm | IDA PMID:19154138 The proline-rich N-terminal sequence of calcineurin Abeta de... | ACCEPT | Summary: Cytoplasmic localization is consistent with established PPP3CA signaling biology [PMID:19154138, PMID:22343722]. Reason: PPP3CA acts on cytoplasmic signaling substrates and scaffolded signaling complexes. |
| GO:0005737 cytoplasm | IDA PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | ACCEPT | Summary: Cytoplasmic localization is consistent with established PPP3CA signaling biology [PMID:19154138, PMID:22343722]. Reason: PPP3CA acts on cytoplasmic signaling substrates and scaffolded signaling complexes. |
| GO:0005955 calcineurin complex | IDA PMID:12218175 Crystal structure of calcineurin-cyclophilin-cyclosporin sho... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0005955 calcineurin complex | IDA PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0005955 calcineurin complex | IDA PMID:23468591 The molecular mechanism of substrate engagement and immunosu... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0005955 calcineurin complex | IDA PMID:27974827 Investigating the human Calcineurin Interaction Network usin... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0006470 protein dephosphorylation | IDA PMID:19154138 The proline-rich N-terminal sequence of calcineurin Abeta de... | ACCEPT | Summary: Protein dephosphorylation is the direct biochemical output of PPP3CA/calcineurin [PMID:15671020, PMID:30718414]. Reason: This accurately reflects catalytic activity on phosphoprotein substrates. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | KEEP AS NON CORE | Summary: PPP3CA can localize on the cytoplasmic side of membrane-associated signaling complexes [PMID:22343722]. Reason: Supported by scaffolded signaling, but context-specific. |
| GO:0033173 calcineurin-NFAT signaling cascade | IDA PMID:19154138 The proline-rich N-terminal sequence of calcineurin Abeta de... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0033173 calcineurin-NFAT signaling cascade | IMP PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0033173 calcineurin-NFAT signaling cascade | IMP PMID:23468591 The molecular mechanism of substrate engagement and immunosu... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IDA PMID:19154138 The proline-rich N-terminal sequence of calcineurin Abeta de... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IDA PMID:23468591 The molecular mechanism of substrate engagement and immunosu... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0043197 dendritic spine | IDA PMID:22343722 Balanced interactions of calcineurin with AKAP79 regulate Ca... | KEEP AS NON CORE | Summary: Dendritic-spine localization is plausible in neuronal signaling contexts [PMID:22343722]. Reason: Supported in specific cellular contexts but not a universal core localization. |
| GO:0005515 protein binding | IPI PMID:12357034 Crystal structure of human calcineurin complexed with cyclos... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005955 calcineurin complex | IDA PMID:12357034 Crystal structure of human calcineurin complexed with cyclos... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0005515 protein binding | IPI PMID:22688515 Na(+)/H(+) exchanger 1 directly binds to calcineurin A and a... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005955 calcineurin complex | IDA PMID:22688515 Na(+)/H(+) exchanger 1 directly binds to calcineurin A and a... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
| GO:0033173 calcineurin-NFAT signaling cascade | IDA PMID:22688515 Na(+)/H(+) exchanger 1 directly binds to calcineurin A and a... | ACCEPT | Summary: PPP3CA is a core mediator of calcineurin-NFAT signaling through NFAT dephosphorylation [PMID:22343722, PMID:26248042, PMID:8631904]. Reason: NFAT-pathway coupling is a principal validated function of calcineurin catalytic subunits. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:22688515 Na(+)/H(+) exchanger 1 directly binds to calcineurin A and a... | KEEP AS NON CORE | Summary: PPP3CA can promote transcription indirectly through NFAT dephosphorylation and nuclear translocation [PMID:22688515]. Reason: Downstream regulatory consequence, not direct transcription-factor molecular function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2025890 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730849 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730867 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730872 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4551451 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4551465 | ACCEPT | Summary: PPP3CA/calcineurin functions in the cytosol in Ca2+-dependent signaling complexes [PMID:22343722]. Reason: Cytosolic localization is consistent with canonical calcineurin signaling and substrate dephosphorylation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2730867 | KEEP AS NON CORE | Summary: Nucleoplasmic context can occur during NFAT-related signaling translocation events (Reactome evidence). Reason: Reasonable pathway-context localization, but less central than cytosolic/calcineurin-complex roles. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4551465 | KEEP AS NON CORE | Summary: Nucleoplasmic context can occur during NFAT-related signaling translocation events (Reactome evidence). Reason: Reasonable pathway-context localization, but less central than cytosolic/calcineurin-complex roles. |
| GO:0006470 protein dephosphorylation | IDA PMID:18815128 CHP2 activates the calcineurin/nuclear factor of activated T... | ACCEPT | Summary: Protein dephosphorylation is the direct biochemical output of PPP3CA/calcineurin [PMID:15671020, PMID:30718414]. Reason: This accurately reflects catalytic activity on phosphoprotein substrates. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | IDA PMID:18815128 CHP2 activates the calcineurin/nuclear factor of activated T... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0051592 response to calcium ion | IDA PMID:18815128 CHP2 activates the calcineurin/nuclear factor of activated T... | ACCEPT | Summary: PPP3CA is activated by intracellular calcium signaling and participates in calcium-responsive pathways. Reason: This broad process term is directionally consistent with calcineurin biology. |
| GO:0005516 calmodulin binding | IDA PMID:11005320 Genetic conservation of the immunophilin-binding domains of ... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0019899 enzyme binding | IDA PMID:11005320 Genetic conservation of the immunophilin-binding domains of ... | KEEP AS NON CORE | Summary: PPP3CA binds multiple enzyme partners/regulators, but this term is broad and secondary to catalytic function. Reason: Retained as non-core due limited specificity. |
| GO:0042110 T cell activation | TAS PMID:11005320 Genetic conservation of the immunophilin-binding domains of ... | KEEP AS NON CORE | Summary: T-cell activation involvement is compatible with canonical calcineurin-immunology biology. Reason: Retained as non-core due pathway-level context and isoform/redundancy considerations. |
| GO:0046983 protein dimerization activity | IPI PMID:11005320 Genetic conservation of the immunophilin-binding domains of ... | REMOVE | Summary: Protein dimerization activity is not a well-supported or informative core MF for PPP3CA. Reason: Evidence better supports regulated complex assembly (calcineurin holoenzyme) rather than standalone dimerization activity. |
| GO:0016311 dephosphorylation | TAS PMID:2556704 Cloning of human calcineurin A: evidence for two isozymes an... | ACCEPT | Summary: Dephosphorylation is the defining catalytic process of PPP3CA/calcineurin. Reason: Accurately reflects direct enzyme activity. |
| GO:0033192 calmodulin-dependent protein phosphatase activity | TAS PMID:2556704 Cloning of human calcineurin A: evidence for two isozymes an... | ACCEPT | Summary: PPP3CA is a calmodulin-dependent serine/threonine phosphatase (calcineurin) [PMID:19154138, PMID:23468591]. Reason: This term captures the specific enzymatic mechanism of PPP3CA. |
| GO:0005515 protein binding | IPI PMID:18838687 Dephosphorylation by calcineurin regulates translocation of ... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:11114196 Calsarcins, a novel family of sarcomeric calcineurin-binding... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0005515 protein binding | IPI PMID:11842093 Calsarcin-3, a novel skeletal muscle-specific member of the ... | REMOVE | Summary: Generic protein-binding annotations from interaction screens are not functionally informative for PPP3CA. Reason: PPP3CA has many interaction partners, but GO:0005515 does not capture its specific calcineurin phosphatase function or pathway role. |
| GO:0006470 protein dephosphorylation | NAS PMID:8392375 Molecular cloning of a full-length cDNA encoding the catalyt... | ACCEPT | Summary: Protein dephosphorylation is the direct biochemical output of PPP3CA/calcineurin [PMID:15671020, PMID:30718414]. Reason: This accurately reflects catalytic activity on phosphoprotein substrates. |
| GO:0004722 protein serine/threonine phosphatase activity | NAS PMID:8392375 Molecular cloning of a full-length cDNA encoding the catalyt... | ACCEPT | Summary: PPP3CA is a protein serine/threonine phosphatase catalytic subunit [PMID:19154138, PMID:30718414]. Reason: This is a core molecular-function annotation directly matching the known enzyme class. |
| GO:0005509 calcium ion binding | NAS PMID:8392375 Molecular cloning of a full-length cDNA encoding the catalyt... | MARK AS OVER ANNOTATED | Summary: Direct calcium-ion binding by PPP3CA catalytic subunit is less specific than calmodulin-dependent activation and holoenzyme regulation. Reason: Annotation is plausible at a broad level but overstates direct, independently informative MF for PPP3CA. |
| GO:0005516 calmodulin binding | NAS PMID:8392375 Molecular cloning of a full-length cDNA encoding the catalyt... | ACCEPT | Summary: Calmodulin binding is central to calcineurin activation and is well supported for PPP3CA [PMID:18384083, PMID:19404396]. Reason: PPP3CA activation requires Ca2+/calmodulin-dependent engagement of its regulatory region, making this a core molecular function. |
| GO:0005955 calcineurin complex | NAS PMID:8392375 Molecular cloning of a full-length cDNA encoding the catalyt... | ACCEPT | Summary: PPP3CA is the catalytic subunit of the calcineurin complex [PMID:12218175, PMID:12357034, PMID:23468591]. Reason: Complex membership is definitive and foundational to PPP3CA biology. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)