MAP KINASE KINASE 5 (MKK5/MEK5; At3g21220) is a group C plant MAPK kinase (MAP2K) of 348 aa that, redundantly with its paralog MKK4, phosphorylates and activates MPK3 and MPK6. Downstream of the MAPKKK YODA, MKK4/MKK5 repress stomatal lineage entry and spacing and, downstream of ERECTA, promote localized cell proliferation in inflorescences; downstream of IDA-HAE/HSL2 they control floral organ abscission; and downstream of pattern-recognition receptors (via MAPKKK5 and related MAPKKKs) they drive immune responses, ethylene and camalexin production and, when constitutively active, hypersensitive-response-like cell death. It is activated by MAPKKK phosphorylation of activation-loop Thr-215/Ser-221; in immunity, MAPKKK3/MAPKKK5 head the cascade downstream of receptors such as the CERK1-PBL27 chitin pathway and FLS2. MKK5 also relays ABA signals from the MAPKKK AIK1 to MPK6. It is a soluble cytoplasmic/nuclear kinase and is recruited to stress granules under stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IEA GO_REF:0000108 | ACCEPT | Summary: Inferred from MAP kinase kinase activity. Reason: MKK5 is the MAPKK in YDA/MAPKKK-MKK4/5-MPK3/6 cascades. Supporting Evidence: PMID:17259259 We further establish that the MKK4/MKK5-MPK3/MPK6 module is downstream of YODA, a MAPKKK. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated protein kinase activity from the kinase domain. Reason: Correct but general; the specific activity is MAP kinase kinase activity. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of protein serine/threonine kinase activity for the MAP2K family. Reason: MKK5 is a dual-specificity MAPKK that phosphorylates the Thr (and Tyr) of the MPK3/MPK6 activation loop; correct parent of MAP kinase kinase activity. Supporting Evidence: PMID:19516975 one well-characterized activation module involves dual phosphorylation of AtMPK3 and AtMPK6 by AtMKK4/5 |
| GO:0004708 MAP kinase kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.7.12.2 mapping to MAP kinase kinase activity. Reason: Core molecular function. Supporting Evidence: PMID:19516975 one well-characterized activation module involves dual phosphorylation of AtMPK3 and AtMPK6 by AtMKK4/5 file:ARATH/MKK5/MKK5-deep-research-falcon.md MKK5’s principal biochemical reaction is **ATP-dependent phosphorylation of downstream protein kinases** |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:11875555 MAP kinase signalling cascade in Arabidopsis innate immunity... | ACCEPT | Summary: MKK5 activity toward MPK3/MPK6 (dual Thr/Tyr phosphorylation). Reason: Dual-specificity MAPKK activity; consistent, though MAP kinase kinase activity is the informative term. Supporting Evidence: PMID:11875555 Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2 |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based protein tyrosine kinase activity. Reason: MAPKKs are dual-specificity kinases that phosphorylate the activation-loop tyrosine of their MAPK targets; consistent, though MAP kinase kinase activity is the informative term. Supporting Evidence: PMID:19516975 one well-characterized activation module involves dual phosphorylation of AtMPK3 and AtMPK6 by AtMKK4/5 |
| GO:0005515 protein binding | IPI PMID:19513235 Comprehensive analysis of protein-protein interactions betwe... | MODIFY | Summary: Interaction with MPK3/MPK6, the downstream MAP kinases. Reason: MKK4/MKK5 bind and phosphorylate MPK3/MPK6; MAP kinase binding is the informative replacement for generic protein binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:19513235 we used the yeast two-hybrid system to conduct a directed protein-protein interaction screen between all the Arabidopsis MPKs and their upstream activators (MAPK kinases; MKK) |
| GO:0005515 protein binding | IPI PMID:25843888 The BASL polarity protein controls a MAPK signaling feedback... | REMOVE | Summary: Interaction with the polarity scaffold BASL (Q5BPF3). Reason: Generic protein binding is uninformative; the partner is not part of a characterized function of this MAPKK that a specific molecular-function term would capture. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:27679653 The Arabidopsis CERK1-associated kinase PBL27 connects chiti... | MODIFY | Summary: MKK5 interacts with MAPKKK5 (Q9C5H5). Reason: Upstream MAPKKK-MAPKK interaction; MAPKKK binding is informative. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:27679653 In addition, MAPKKK5 interacts with MKK4 and MKK5 in vivo and phosphorylates their activation loops. |
| GO:0005515 protein binding | IPI PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | MODIFY | Summary: Interaction with MPK3/MPK6, the downstream MAP kinases. Reason: MKK4/MKK5 bind and phosphorylate MPK3/MPK6; MAP kinase binding is the informative replacement for generic protein binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:27913741 Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. |
| GO:0005515 protein binding | IPI PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | MODIFY | Summary: Interaction with MPK3/MPK6, the downstream MAP kinases. Reason: MKK4/MKK5 bind and phosphorylate MPK3/MPK6; MAP kinase binding is the informative replacement for generic protein binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:27913741 Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. |
| GO:0005515 protein binding | IPI PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | MODIFY | Summary: MKK5 interacts with the MAPKKK AIK1 (Q9SND6). Reason: Upstream MAPKKK interaction; MAPKKK binding is informative. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:27913741 Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. |
| GO:0005515 protein binding | IPI PMID:32612234 Extensive signal integration by the phytohormone protein net... | MODIFY | Summary: Interaction with MPK3/MPK6, the downstream MAP kinases. Reason: MKK4/MKK5 bind and phosphorylate MPK3/MPK6; MAP kinase binding is the informative replacement for generic protein binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:19516975 one well-characterized activation module involves dual phosphorylation of AtMPK3 and AtMPK6 by AtMKK4/5 |
| GO:0005515 protein binding | IPI PMID:37950543 Phosphoproteome analyses pinpoint the F-box protein SLOW MOT... | REMOVE | Summary: Interaction with the F-box protein SLOMO (AT4G33210). Reason: Generic protein binding is uninformative; the partner is not part of a characterized function of this MAPKK that a specific molecular-function term would capture. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:39923935 Identifying Receptor Kinase Substrates Using an 8000 Peptide... | REMOVE | Summary: Interaction with the receptor-like kinase ILK4 (AT3G58760). Reason: Generic protein binding is uninformative; the partner is not part of a characterized function of this MAPKK that a specific molecular-function term would capture. Removal does not imply the interaction is false. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding inferred from the kinase domain. Reason: Required for catalysis. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of cytoplasm. Reason: Soluble cascade kinase; consistent with paralog MKK4 localization. |
| GO:0005739 mitochondrion | ISM GO_REF:0000122 | MARK AS OVER ANNOTATED | Summary: Sequence-model (AtSubP) prediction of mitochondrion. Reason: No experimental support for a mitochondrial pool; MKK5 interacts with its MAPKKK activator and acts on MPK3/MPK6 mainly in the cytosol. The N-terminal extension, which ChloroP predicts as a chloroplast transit sequence (the paralog MKK4 is imported into the plastid stroma in vitro), likely drove the organellar prediction; nothing points to mitochondria. One independent review proposed REMOVE; kept as over-annotated because an N-terminal organellar targeting signal is genuinely predicted and organellar import of MKK5 has not been tested. Supporting Evidence: PMID:19516975 at least two members, MKK4 and MKK5, were predicted to contain a chloroplast transit sequence PMID:27679653 MAPKKK5 interacts with MKK2, MKK4, and MKK5 mainly in the cytosol |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of signal transduction. Reason: Correct; the specific process is the MAPK cascade. Supporting Evidence: PMID:17259259 We further establish that the MKK4/MKK5-MPK3/MPK6 module is downstream of YODA, a MAPKKK. |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of signal transduction. Reason: Correct, general. |
| GO:0009626 plant-type hypersensitive response | IMP PMID:18268539 Ethylene signaling is required for the acceleration of cell ... | KEEP AS NON CORE | Summary: Activation of MEK5(DD) induces HR-like cell death. Reason: Gain-of-function phenotype reflecting immune MAPK output; non-core. Supporting Evidence: PMID:18268539 the activation of AtMEK5, a MAPK kinase, can in turn activate endogenous AtMAPK3 and AtMAPK6, and can lead to a striking increase in ethylene production and induce hypersensitive response (HR)-like cell death in Arabidopsis |
| GO:0009738 abscisic acid-activated signaling pathway | IMP PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | KEEP AS NON CORE | Summary: MKK5 acts in the AIK1-MKK5-MPK6 ABA module. Reason: Abstract-level evidence; secondary signalling context. Supporting Evidence: PMID:27913741 Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. |
| GO:0010082 regulation of root meristem growth | IMP PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | KEEP AS NON CORE | Summary: AIK1-MKK5 module affects ABA regulation of root growth. Reason: Secondary output; abstract only. Supporting Evidence: PMID:27913741 AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. |
| GO:0010227 floral organ abscission | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction of floral organ abscission. Reason: Supported experimentally (IDA-HAE/HSL2-MKK4/5-MPK3/6); a developmental output of the cascade. Supporting Evidence: PMID:18809915 the Mitogen-Activated Protein Kinase Kinase 4 (MKK4) and MKK5, and a dominant-negative form of Mitogen-Activated Protein Kinase 6 (MPK6) in a mpk3 mutant background all have abscission-defective phenotypes |
| GO:0010227 floral organ abscission | IMP PMID:18809915 Regulation of floral organ abscission in Arabidopsis thalian... | KEEP AS NON CORE | Summary: MKK4/MKK5 RNAi lines are abscission defective; constitutively active MKKs rescue hae hsl2. Reason: Genuine developmental role downstream of HAE/HSL2; non-core relative to the kinase activity. Supporting Evidence: PMID:18809915 the Mitogen-Activated Protein Kinase Kinase 4 (MKK4) and MKK5, and a dominant-negative form of Mitogen-Activated Protein Kinase 6 (MPK6) in a mpk3 mutant background all have abscission-defective phenotypes |
| GO:0010227 floral organ abscission | IMP PMID:25730871 Floral organ abscission is regulated by a positive feedback ... | KEEP AS NON CORE | Summary: MKK4/5-dependent phosphorylation of AGL15 in the HAE positive feedback loop. Reason: Abstract-level evidence consistent with the established abscission role. Supporting Evidence: PMID:25730871 AGL15 is then differentially phosphorylated through development in floral receptacles in a MITOGEN-ACTIVATED PROTEIN KINASE KINASE 4/5-dependent manner. |
| GO:0010229 inflorescence development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction of inflorescence development. Reason: Supported by ERECTA-YDA-MKK4/5 genetics; developmental output. Supporting Evidence: PMID:23263767 Loss-of-function mutants of MPK3 / MPK6 and MKK4 / MKK5 phenocopy the er mutant, whereas the gain-of-function MKK4 and MKK5 transgenes can rescue the er mutant at both morphological and cellular levels |
| GO:0010229 inflorescence development | IGI PMID:23263767 A MAPK cascade downstream of ERECTA receptor-like protein ki... | KEEP AS NON CORE | Summary: mkk4 mkk5 loss phenocopies erecta; active MKK4/5 rescue er. Reason: Valid developmental output of the ERECTA-YDA-MKK4/5-MPK3/6 module. Supporting Evidence: PMID:23263767 Loss-of-function mutants of MPK3 / MPK6 and MKK4 / MKK5 phenocopy the er mutant, whereas the gain-of-function MKK4 and MKK5 transgenes can rescue the er mutant at both morphological and cellular levels |
| GO:0010365 positive regulation of ethylene biosynthetic process | IMP PMID:18268539 Ethylene signaling is required for the acceleration of cell ... | KEEP AS NON CORE | Summary: Active MEK5 increases ethylene production. Reason: Downstream output via MPK3/MPK6-mediated ACS stabilization; non-core. Supporting Evidence: PMID:18268539 the activation of AtMEK5, a MAPK kinase, can in turn activate endogenous AtMAPK3 and AtMAPK6, and can lead to a striking increase in ethylene production and induce hypersensitive response (HR)-like cell death in Arabidopsis |
| GO:0010494 cytoplasmic stress granule | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference of stress granule localization. Reason: Based on stress-granule proteomics; a stress-conditional pool of unclear function. |
| GO:0010494 cytoplasmic stress granule | IDA PMID:30664249 Protein and metabolite composition of Arabidopsis stress gra... | KEEP AS NON CORE | Summary: MKK5 identified in affinity-purified stress granules. Reason: Proteomic detection in a stress-granule proteome; conditional localization of unclear functional significance. The cached text is abstract-only and does not name MKK5; the MKK5-specific identification is in the paper's supplementary protein tables, which are not available in the cache, so the annotation is kept (non-core) deferring to the curator. The quoted text documents only the isolation method; no independent cached evidence places MKK5 in stress granules. Supporting Evidence: PMID:30664249 To isolate SGs we used Arabidopsis seedlings expressing green fluorescent protein (GFP) fusion of the SGs marker protein, Rbp47b, and an experimental protocol combining differential centrifugation with affinity purification (AP). |
| GO:0051301 cell division | IMP PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | MARK AS OVER ANNOTATED | Summary: Root cell division phenotype in the ABA module. Reason: MKK5 regulates, but does not participate in, cell division; the regulatory root-growth annotation captures this. The cell-division phenotype is reported for aik1; mkk5 mutants phenocopy aik1 and constitutively active MKK5 rescues aik1, placing MKK5 in the same pathway. Supporting Evidence: PMID:27913741 AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. PMID:27913741 The single mutant seedlings of mpk6 and mkk5 have similar phenotypes to aik1 , but mkk4 does not. PMID:27913741 Constitutively active MKK5 in aik1 mutant seedlings complements the ABA-insensitive root growth phenotype of aik1 . |
| GO:0051510 regulation of unidimensional cell growth | IMP PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | KEEP AS NON CORE | Summary: Root cell elongation phenotype in the ABA module. Reason: Secondary regulatory output. The root cell-elongation phenotype is reported for aik1; mkk5 mutants phenocopy aik1 and constitutively active MKK5 rescues the aik1 root-growth phenotype, placing MKK5 in this AIK1-MKK5-MPK6 regulatory pathway. Supporting Evidence: PMID:27913741 AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. PMID:27913741 The single mutant seedlings of mpk6 and mkk5 have similar phenotypes to aik1 , but mkk4 does not. PMID:27913741 Constitutively active MKK5 in aik1 mutant seedlings complements the ABA-insensitive root growth phenotype of aik1 . |
| GO:0090333 regulation of stomatal closure | IMP PMID:27913741 AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic... | KEEP AS NON CORE | Summary: Stomatal ABA response phenotype in the AIK1-MKK5 module. Reason: Secondary physiological output. Supporting Evidence: PMID:27913741 AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. |
| GO:0098542 defense response to other organism | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of defense response for the MKK4/MKK5/MKK9-type node. Reason: Immune signalling downstream of pattern-recognition receptors is a principal role of the MKK4/MKK5 pair. Supporting Evidence: PMID:11875555 Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2 |
| GO:0098542 defense response to other organism | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of defense response to other organism. Reason: Consistent with experimental evidence. Supporting Evidence: PMID:11875555 Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2 |
| GO:0098542 defense response to other organism | IMP PMID:11875555 MAP kinase signalling cascade in Arabidopsis innate immunity... | ACCEPT | Summary: MKK4/MKK5 act in the flagellin-triggered MAPK cascade conferring resistance. Reason: Principal immune role of the cascade. Supporting Evidence: PMID:11875555 Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2 PMID:11875555 Activation of this MAPK cascade confers resistance to both bacterial and fungal pathogens |
| GO:0106310 protein serine kinase activity | EXP PMID:11875555 MAP kinase signalling cascade in Arabidopsis innate immunity... | MODIFY | Summary: Protein serine kinase activity derived from the UniProt Rhea expansion of EC 2.7.12.2 citing Asai et al. 2002, where MKK5 activates MPK3/MPK6 in protoplasts. Reason: The activity demonstrated for MKK5 is dual-specificity phosphorylation and activation of MPK3/MPK6 (Thr and Tyr of the TEY activation motif); the serine-specific label is an artefact of the EC 2.7.12.2-to-Rhea expansion rather than an observed phosphoserine product. The evidence supports MAP kinase kinase activity. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:18268539 the activation of AtMEK5, a MAPK kinase, can in turn activate endogenous AtMAPK3 and AtMAPK6 PMID:11875555 Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: Protein serine kinase activity from the Rhea:17989 mapping of EC 2.7.12.2. Reason: EC 2.7.12.2 expansion; the biologically relevant activity is MAP kinase kinase activity on the Thr/Tyr of the MPK3/MPK6 activation loop, not serine phosphorylation. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:19516975 one well-characterized activation module involves dual phosphorylation of AtMPK3 and AtMPK6 by AtMKK4/5 |
| GO:2000122 negative regulation of stomatal complex development | IGI PMID:17259259 Stomatal development and patterning are regulated by environ... | NEW | Summary: Loss of MKK4/MKK5 causes stomatal clustering; activation suppresses stomatal fate. Reason: MKK5 (redundantly with its paralog MKK4) performs the phosphorylation step that relays YODA signalling to MPK3/MPK6, which inhibit SPEECHLESS; it does part of the work of this regulatory process. Supporting Evidence: PMID:17259259 Loss of function of MKK4/MKK5 or MPK3/MPK6 disrupts the coordinated cell fate specification of stomata versus pavement cells, resulting in the formation of clustered stomata. PMID:17259259 Conversely, activation of MKK4/MKK5-MPK3/MPK6 causes the suppression of asymmetric cell divisions and stomatal cell fate specification, resulting in a lack of stomatal differentiation. |
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Download this section (compressed HTML)Q: How is output specificity achieved when the same MKK4/MKK5 pair relays YODA (stomata, embryo, inflorescence), HAE/HSL2 (abscission) and immune-receptor signals to MPK3/MPK6?
Q: Are MKK4 and MKK5 fully redundant in the stomatal lineage, or do expression-level or docking differences give one paralog a predominant role?
Q: Should the MAPK-cascade members downstream of pattern recognition receptors (MKK4, MKK5, MPK3, MPK6) carry cell surface pattern recognition receptor signaling pathway (GO:0002752)? MAPKKK5 carries it via a curator IGI row, but no same-role MAP2K or MAPK currently does, so it is not proposed here.
Q: Camalexin induction by MKK5 is supported only by gain-of-function (GVG-MKK5DD) data; does mkk4 mkk5 loss of function (conditional or amiRNA lines) compromise pathogen-induced camalexin, which would justify positive regulation of camalexin biosynthetic process (GO:1901183) as on MPK3?
Q: Is the MKK5 contribution to ABA root and guard-cell responses (mkk5 single mutant phenotype, mkk4 not) a genuine non-redundant function, and how is it insulated from the immune and developmental uses of the same MAP2K?
Q: Should EC 2.7.12.2-derived protein serine kinase activity (GO:0106310) rows be suppressed for MAP2Ks whose physiological substrates are the Thr/Tyr of MAPK TEY motifs?
Q: Two independent reviews disagreed on the MPK3/MPK6 and MAPKKK interaction rows (MODIFY to MAP kinase binding / MAPKKK binding versus REMOVE as kinase-substrate interactions already captured by MAP kinase kinase activity). Should docking interactions of a MAP2K with its MAPKKK activator and MAPK substrates be captured as specific binding terms, or only via the catalytic activity?
Experiment: Generate clean mkk4 mkk5 CRISPR double mutants with cell-type-specific complementation (SPCH or MUTE promoters) to test where in the stomatal lineage MKK4/5 activity is required, avoiding RNAi silencing variability.
Type: genetics / cell-type-specific complementation
Experiment: Phosphosite mapping (LC-MS/MS) of MPK3/MPK6 phosphorylated by MAPKKK5-activated wild-type MKK5 to confirm dual Thr/Tyr specificity and test for any serine phosphorylation of physiological substrates.
Experiment: Conditional (estradiol-inducible amiRNA) depletion of MKK4 in mkk5 backgrounds to separate immune (chitin, flg22) from developmental requirements, assaying MPK3/MPK6 activation, camalexin accumulation and resistance to Botrytis cinerea.
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