CIPK24 (also known as SOS2, SALT OVERLY SENSITIVE 2; SnRK3.11) is a calcium-regulated serine/threonine protein kinase of the SnRK3/CIPK (CBL-INTERACTING PROTEIN KINASE) family and the central kinase of the SOS salt-stress signaling pathway in Arabidopsis. It comprises an N-terminal SNF1/AMPK-like catalytic kinase domain and a C-terminal regulatory region containing a NAF/FISL autoinhibitory motif and a PPI motif. In the resting state the kinase is autoinhibited; binding of a Ca2+-loaded calcineurin-B-like (CBL) calcium sensor to the NAF motif relieves autoinhibition and activates the kinase in a calcium-dependent manner. CBL4/SOS3 (myristoylated, EF-hand) recruits and activates the kinase at the plasma membrane, where the CBL4-CIPK24 complex phosphorylates the autoinhibitory C-terminus of the plasma-membrane Na+/H+ antiporter SOS1/NHX7 to drive Na+ extrusion, while CBL10 recruits the kinase to the tonoplast to regulate vacuolar Na+ sequestration. The kinase also phosphorylates its activating CBL partners (e.g. CBL10/SCaBP8), binds the PP2C phosphatase ABI2 (a negative regulator) through its PPI motif, and connects to additional salt- and reactive-oxygen-signaling factors. Through these activities CIPK24 maintains intracellular Na+/K+ homeostasis and confers salt-stress tolerance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: General protein kinase activity, electronically inferred from InterPro kinase domains. Correct but less specific than the experimentally supported serine/threonine kinase activity; the same activity is independently supported by IDA (PMID:10725382). Reason: CIPK24 is a genuine active kinase with an N-terminal SNF1-like catalytic domain; autophosphorylation demonstrates protein kinase activity. This is a core molecular function. Supporting Evidence: PMID:10725382 Autophosphorylation assays show that SOS2 is an active protein kinase. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Protein serine/threonine kinase activity, the specific catalytic activity of CIPK24/SOS2 (EC 2.7.11.1). Experimentally established kinetics (KM, Vmax) and Mn2+ cofactor are documented in UniProt; SOS2 phosphorylates Ser/Thr residues on SOS1, CBL proteins and synthetic substrates. Reason: This is the precise, experimentally supported core molecular function of the gene. Supporting Evidence: PMID:10725382 SOS2 is predicted to encode a serine/threonine type protein kinase with file:ARATH/CIPK24/CIPK24-uniprot.txt O-phospho-L-seryl-[protein] + ADP + file:ARATH/CIPK24/CIPK24-deep-research-falcon.md SOS2/CIPK24 is a Ser/Thr kinase with an N-terminal catalytic domain and a C-terminal regulatory region typical of SnRK3/CIPKs. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding, electronically inferred from the kinase ATP-binding site. Consistent with the catalytic mechanism (ATP is the phosphate donor) and the experimentally defined catalytic Lys-40 whose mutation abolishes autophosphorylation. Reason: ATP binding is integral to the core kinase activity; supported by the conserved ATP-binding lysine and by abolition of activity in the K40N mutant. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt K->N: Abolishes autophosphorylation. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization, mapped electronically from the UniProt subcellular location. A nuclear pool of SOS2 is biologically supported by its role in a nuclear salt-body SOS2-PIF4 module, but localization is largely partner-dependent (cytoplasm/membranes). Reason: Nucleus is a genuine but secondary location; the core salt-tolerance function is executed at the plasma membrane and tonoplast. Recent work supports a distinct nuclear role. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt Nucleus PMID:40726285 assembling the SALT OVERLY SENSITIVE 2 (SOS2)-PIF4 complex in the same salt body |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasmic localization mapped from the UniProt subcellular location. SOS2 is cytoplasmic in the resting state and is recruited to membranes upon CBL binding. Reason: Cytoplasm is the resting/default compartment; correct but not the site of the core catalytic function, which occurs after recruitment to membranes. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt Cytoplasm file:ARATH/CIPK24/CIPK24-deep-research-falcon.md SOS2 alone is generally cytoplasmic (and in broader CIPK reviews, often nucleoplasmic), but active localization is strongly partner-dependent. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Signal transduction, electronically inferred from the NAF domain. True at a high level (SOS2 is the kinase node of CBL-CIPK calcium signaling) but uninformatively broad. Reason: The specific role is calcium-mediated CBL-CIPK signaling driving ion homeostasis; the bare 'signal transduction' term adds little. More specific salt-stress and ion-transport regulation terms capture the function. Supporting Evidence: PMID:10725350 SOS3 and SOS2 define a novel regulatory pathway important for the control of intracellular ion homeostasis and salt tolerance in plants |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity, inferred from RHEA mapping of the Ser-phosphorylation reaction (EC 2.7.11.1). A specific sub-activity consistent with the experimentally established Ser/Thr kinase function. Reason: Correct specific catalytic activity; CIPK24 phosphorylates serine residues (e.g. Ser-237 of SCaBP8/CBL10) and the SOS1 C-terminus. Core function. Supporting Evidence: PMID:19448033 SOS2 phosphorylates SCaBP8 at its C terminus |
| GO:0005515 protein binding | IPI PMID:10725350 The Arabidopsis SOS2 protein kinase physically interacts wit... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL4/SOS3 (UniProtKB O81223). The interaction is the functionally critical, calcium-dependent activation of SOS2 by SOS3 via the C-terminal NAF motif. The bare 'protein binding' term is uninformative for the specific role. Reason: Per curation guidelines the generic protein binding term is not informative as a core function; however the underlying CBL4/SOS3 interaction is real and central (Ca2+-dependent kinase activation) and is captured in core_functions and notes. Not removed because valid experimental IPI evidence exists. Supporting Evidence: PMID:10725350 SOS3 physically interacts with and activates SOS2 protein kinase |
| GO:0005515 protein binding | IPI PMID:11006339 SOS3 function in plant salt tolerance requires N-myristoylat... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL4/SOS3 (UniProtKB O81223). This paper centers on SOS3 N-myristoylation/calcium binding; the mapped pair is the SOS2-SOS3 interaction. Reason: Generic protein binding is uninformative; the specific SOS2-SOS3 interaction is already represented. Valid IPI evidence, so not removed. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt O81223: CBL4 |
| GO:0005515 protein binding | IPI PMID:11402167 Molecular characterization of functional domains in the prot... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL4/SOS3 (O81223) and CBL1 (O81445), characterizing the 21-aa NAF/SOS3-binding motif that also serves as the autoinhibitory domain. Reason: The generic term is uninformative; the underlying NAF-mediated CBL binding and autoinhibition mechanism are core and captured elsewhere. Valid IPI evidence. Supporting Evidence: PMID:11402167 a 21-amino acid motif in the regulatory domain of SOS2 that is necessary and sufficient for interaction with SOS3 |
| GO:0005515 protein binding | IPI PMID:14504388 A novel domain in the protein kinase SOS2 mediates interacti... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to the PP2C phosphatase ABI2 (UniProtKB O04719) via the SOS2 PPI motif. ABI2 is a negative regulator of the SOS pathway. Reason: Generic protein binding is uninformative; the specific, mechanistically important ABI2 interaction is captured in the reason/notes. Valid experimental IPI evidence. Supporting Evidence: PMID:14504388 the protein phosphatase interaction (PPI) motif, of SOS2 that is necessary and sufficient for interaction with ABI2 |
| GO:0005515 protein binding | IPI PMID:14730064 Calcium sensors and their interacting protein kinases: genom... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL1 (O81445) and CBL9 (Q9LTB8) from the CBL-CIPK network genomics study. Establishes CIPK24 as a CBL-interacting kinase. Reason: Generic term uninformative; specific CBL interactions captured in core_functions. Valid IPI evidence (note this reference now carries an Expression of Concern). Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt Q9LTB8: CBL9 |
| GO:0005515 protein binding | IPI PMID:17360592 Differential binding of calmodulin-related proteins to their... | MARK AS OVER ANNOTATED | Summary: High-density protein microarray detected binding to calmodulin-related proteins CAM7 (P59220) and CML9 (Q9S744). These are high-throughput interactions of uncertain physiological relevance to the core salt pathway. Reason: Generic protein binding is uninformative, and these calmodulin-microarray hits are peripheral to the established function. Valid experimental evidence, so not removed. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt P59220: CAM7 |
| GO:0005515 protein binding | IPI PMID:17449811 SCABP8/CBL10, a putative calcium sensor, interacts with the ... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL4/SOS3 (O81223) and CBL10/SCABP8 (Q7FRS8). CBL10 recruits SOS2 and enhances its activity in a calcium-dependent manner (shoot salt response). Reason: Generic term uninformative; the functionally important CBL10/SCABP8 recruitment and activation is captured in core_functions. Valid IPI evidence. Supporting Evidence: PMID:17449811 recruit SOS2 to the plasma membrane, enhance SOS2 activity in a calcium-dependent manner, and activate SOS1 in yeast |
| GO:0005515 protein binding | IPI PMID:17785451 Interaction of SOS2 with nucleoside diphosphate kinase 2 and... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to NDPK2 (O64903) and CBL4/SOS3 (O81223). SOS2 interacts with and inhibits NDPK2, linking salt stress and H2O2 signaling. Reason: Generic protein binding is uninformative; the NDPK2 interaction is a secondary (reactive-oxygen) branch captured in notes. Valid experimental IPI evidence. Supporting Evidence: PMID:17785451 SOS2 was found to interact with the H2O2 signaling protein nucleoside diphosphate kinase 2 (NDPK2) |
| GO:0005515 protein binding | IPI PMID:17825054 The calcium sensor CBL10 mediates salt tolerance by regulati... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL10 (Q7FRS8). The CBL10-CIPK24 complex localizes to vacuolar membranes and mediates Na+ sequestration in shoots. Reason: Generic term uninformative; the specific CBL10 interaction and tonoplast targeting are captured in core_functions and the IDA vacuole-membrane annotation. Valid IPI evidence. Supporting Evidence: PMID:17825054 the CBL10-CIPK24 (SOS2) complex is associated with the vacuolar compartments |
| GO:0005515 protein binding | IPI PMID:19448033 Phosphorylation of SOS3-LIKE CALCIUM BINDING PROTEIN8 by SOS... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL10 isoform SCaBP8 (Q7FRS8-2). SOS2 both binds and phosphorylates SCaBP8/CBL10 at Ser-237, stabilizing the complex and enhancing Na+/H+ exchange. Reason: Generic protein binding is uninformative; the binding plus phosphorylation of CBL10 is captured in core_functions/kinase activity. Valid experimental IPI evidence. Supporting Evidence: PMID:19448033 stabilized the SCaBP8-SOS2 interaction, and enhanced plasma membrane Na+/H+ exchange activity |
| GO:0005515 protein binding | IPI PMID:21262798 Activation of the plasma membrane Na/H antiporter Salt-Overl... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding to CBL4/SOS3 (O81223) and to the substrate SOS1/NHX7 (Q9LKW9). SOS2-SOS3 phosphorylates the SOS1 autoinhibitory C-terminus to activate Na+/H+ exchange. Reason: Generic term uninformative; the SOS1 substrate interaction is the key downstream event and is captured in core_functions. Valid experimental IPI evidence, not removed. Supporting Evidence: PMID:21262798 SOS1 is relieved from auto-inhibition upon phosphorylation of the auto-inhibitory domain by SOS2-SOS3 |
| GO:0005515 protein binding | IPI PMID:21798944 Evidence for network evolution in an Arabidopsis interactome... | MARK AS OVER ANNOTATED | Summary: Large-scale Arabidopsis interactome map; IntAct maps binding to CBL1 (O81445). A high-throughput interaction consistent with CIPK24 being a CBL-interacting kinase. Reason: Generic protein binding is uninformative and derives from a high-throughput screen; the CBL1 interaction is already represented. Valid IPI evidence. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt O81445: CBL1 |
| GO:0005515 protein binding | IPI PMID:32612234 Extensive signal integration by the phytohormone protein net... | MARK AS OVER ANNOTATED | Summary: Hormone/phytohormone protein interactome study; IntAct maps binding to CBL1 (O81445) and CBL9 (Q9LTB8). High-throughput interactions with CBL calcium sensors. Reason: Generic protein binding is uninformative; the CBL1/CBL9 interactions are already represented in core_functions. Valid IPI evidence. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt Q9LTB8: CBL9 |
| GO:0005515 protein binding | IPI PMID:40726285 Salt-responsive SSN1 condensation in nucleus facilitates PIF... | MARK AS OVER ANNOTATED | Summary: TAIR-curated interaction with SSN1 (AT2G36080); SOS2 co-condenses with SSN1 and PIF4 in nuclear salt bodies, facilitating PIF4 degradation. A nuclear branch of SOS2 function. Reason: Generic protein binding is uninformative; the specific SSN1/PIF4 nuclear interaction is captured in notes and supports the nucleus localization. Valid experimental evidence. Supporting Evidence: PMID:40726285 assembling the SALT OVERLY SENSITIVE 2 (SOS2)-PIF4 complex in the same salt body |
| GO:0005737 cytoplasm | ISM GO_REF:0000122 | KEEP AS NON CORE | Summary: Cytoplasmic localization predicted by AtSubP (sequence-based ISM). Redundant with the UniProt-derived cytoplasm annotation and consistent with the resting-state localization. Reason: Correct but a sequence-based prediction; cytoplasm is the resting compartment, not the site of core catalytic function. Supporting Evidence: file:ARATH/CIPK24/CIPK24-uniprot.txt Cytoplasm |
| GO:0009705 plant-type vacuole membrane | IDA PMID:17825054 The calcium sensor CBL10 mediates salt tolerance by regulati... | KEEP AS NON CORE | Summary: Tonoplast (plant-type vacuole membrane) localization of the CBL10-CIPK24 complex, experimentally observed (IDA). This is where SOS2 acts in vacuolar Na+ sequestration when partnered with CBL10. Reason: A genuine, experimentally observed, partner-dependent localization relevant to the shoot/vacuolar branch of salt tolerance; meaningful but secondary to plasma-membrane action. Supporting Evidence: PMID:17825054 the CBL10-CIPK24 (SOS2) complex is associated with the vacuolar compartments |
| GO:0004672 protein kinase activity | IDA PMID:10725382 The Arabidopsis thaliana SOS2 gene encodes a protein kinase ... | ACCEPT | Summary: Direct experimental demonstration (IDA) of protein kinase activity via SOS2 autophosphorylation; kinase-dead mutations (K40N, G197E) abolish it. This is the strongest evidence for the core catalytic function. Reason: Experimentally proven core molecular function. A more specific Ser/Thr kinase term is also annotated; both are appropriate. Supporting Evidence: PMID:10725382 Autophosphorylation assays show that SOS2 is an active protein kinase. |
| GO:0009651 response to salt stress | IMP PMID:9668136 Genetic analysis of salt tolerance in arabidopsis. Evidence ... | ACCEPT | Summary: Mutant phenotype evidence (IMP) shows sos2 plants are specifically hypersensitive to Na+/Li+ and impaired in K+ nutrition, defining SOS2 as a salt-tolerance determinant. This is the defining biological process for the gene. Reason: Core biological process, supported by the founding genetic screen and the entire downstream mechanistic literature. Supporting Evidence: PMID:9668136 sos2 mutants are specifically hypersensitive to inhibition by Na+ or Li+ and not hypersensitive to general osmotic stresses file:ARATH/CIPK24/CIPK24-deep-research-falcon.md SOS2 is required for salt tolerance |
| GO:0002028 regulation of sodium ion transport | IMP PMID:21262798 Activation of the plasma membrane Na/H antiporter Salt-Overl... | NEW | Summary: Proposed new annotation. CIPK24/SOS2, as the SOS2-SOS3 complex, phosphorylates and relieves autoinhibition of the plasma-membrane Na+/H+ antiporter SOS1, directly up-regulating Na+ efflux. This specific regulation of sodium transport is better captured by this term than by the generic 'signal transduction'. Reason: Mechanistically supported regulation of sodium ion transport via SOS1 activation; a core downstream function not currently in GOA. Supporting Evidence: PMID:21262798 SOS1 is relieved from auto-inhibition upon phosphorylation of the auto-inhibitory domain by SOS2-SOS3 file:ARATH/CIPK24/CIPK24-deep-research-falcon.md The strongest direct substrate relationship is between SOS2 and the plasma membrane Na\(^+\)/H\(^+\) exchanger SOS1 |
| GO:0006883 intracellular sodium ion homeostasis | IMP PMID:10725382 The Arabidopsis thaliana SOS2 gene encodes a protein kinase ... | NEW | Summary: Proposed new annotation. SOS2 is required for maintenance of intracellular Na+ (and K+) homeostasis; sos2 mutants show Na+/K+ imbalance. Captures the homeostatic outcome of the SOS pathway more specifically than 'response to salt stress' alone. Reason: Directly supported intracellular sodium ion homeostasis role; core function not currently in GOA. Supporting Evidence: PMID:10725382 the Salt Overly Sensitive 2 (SOS2) gene is required for intracellular Na(+) and K(+) homeostasis |
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Download this section (compressed HTML)Q: Beyond SOS1 and the CBL sensors, what is the full physiological substrate repertoire of CIPK24 (e.g. CAX1, AKT-type K+ channels, NDPK2), and which are direct in vivo targets?
Q: How do plasma-membrane (CBL4/SOS3) versus tonoplast (CBL10) recruitment quantitatively partition CIPK24 activity between Na+ extrusion and vacuolar Na+ sequestration in different tissues?
Q: What is the in vivo significance and regulation of the recently described nuclear SOS2-PIF4 salt-body branch relative to the canonical membrane-transport role?
Experiment: Phosphoproteomics of wild-type versus sos2 plants under salt stress to define the in vivo CIPK24 substrate network.
Experiment: Quantitative co-localization and activity assays of CBL4/SOS3-CIPK24 (plasma membrane) versus CBL10-CIPK24 (tonoplast) complexes to map spatial control of ion transport.
Experiment: Structure-guided separation-of-function mutants (NAF motif, PPI motif, activation-loop Thr-168) to dissect activation, phosphatase regulation, and substrate selection in planta.
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