AHK4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000155 phosphorelay sensor kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: AHK4 is a CHASE-domain hybrid sensor histidine kinase that autophosphorylates on its conserved transmitter-domain histidine and relays the phosphoryl group via its receiver domain to AHP phosphotransfer proteins. Reason: Phosphorelay sensor kinase activity is the core catalytic function of the cytokinin receptors and is directly supported by cytokinin-dependent kinase/phosphorelay assays in yeast and E. coli. Supporting Evidence: PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin PMID:14503005 Cytokinins are perceived by three histidine kinases--CRE1/WOL/AHK4, AHK2, and AHK3--which initiate intracellular phosphotransfer.
GO:0000155 phosphorelay sensor kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: AHK4 is a CHASE-domain hybrid sensor histidine kinase that autophosphorylates on its conserved transmitter-domain histidine and relays the phosphoryl group via its receiver domain to AHP phosphotransfer proteins. Reason: Phosphorelay sensor kinase activity is the core catalytic function of the cytokinin receptors and is directly supported by cytokinin-dependent kinase/phosphorelay assays in yeast and E. coli. Supporting Evidence: PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin PMID:14503005 Cytokinins are perceived by three histidine kinases--CRE1/WOL/AHK4, AHK2, and AHK3--which initiate intracellular phosphotransfer.
GO:0000160 phosphorelay signal transduction system	IBA GO_REF:0000033	ACCEPT	Summary: AHK4 initiates the multistep His-Asp phosphorelay (AHK -> AHP -> ARR) that transduces the cytokinin signal. Reason: Participation in phosphorelay signal transduction is the defining role of the CRE-family receptors. Supporting Evidence: PMID:12068096 A multistep two-component phosphorelay system with distinct AHK, AHP, and ARR proteins plays a central role in cytokinin signal transduction PMID:11230563 a phosphorelay interaction between the Arabidopsis His-kinase and histidine-containing phosphotransmitters (AHPs) was also demonstrated for the first time
GO:0000160 phosphorelay signal transduction system	IDA PMID:11230563 The Arabidopsis sensor His-kinase, AHk4, can respond to cyto...	ACCEPT	Summary: AHK4 initiates the multistep His-Asp phosphorelay (AHK -> AHP -> ARR) that transduces the cytokinin signal. Reason: Participation in phosphorelay signal transduction is the defining role of the CRE-family receptors. Supporting Evidence: PMID:12068096 A multistep two-component phosphorelay system with distinct AHK, AHP, and ARR proteins plays a central role in cytokinin signal transduction PMID:11230563 a phosphorelay interaction between the Arabidopsis His-kinase and histidine-containing phosphotransmitters (AHPs) was also demonstrated for the first time
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	ACCEPT	Summary: AHK4 initiates the multistep His-Asp phosphorelay (AHK -> AHP -> ARR) that transduces the cytokinin signal. Reason: Participation in phosphorelay signal transduction is the defining role of the CRE-family receptors. Supporting Evidence: PMID:12068096 A multistep two-component phosphorelay system with distinct AHK, AHP, and ARR proteins plays a central role in cytokinin signal transduction PMID:11230563 a phosphorelay interaction between the Arabidopsis His-kinase and histidine-containing phosphotransmitters (AHPs) was also demonstrated for the first time
GO:0004673 protein histidine kinase activity	EXP PMID:11479382 The AHK4 gene involved in the cytokinin-signaling pathway as...	ACCEPT	Summary: AHK4 has protein histidine kinase activity (autophosphorylation and phosphotransfer to AHPs), stimulated by cytokinin binding. Reason: Histidine kinase activity of the CRE-family receptors is established biochemically (cytokinin-dependent kinase activity in yeast/E. coli and in vitro). Supporting Evidence: PMID:11479382 AHK4 expressed in budding yeast showed histidine kinase activity in a manner dependent on the presence of cytokinin PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin
GO:0004673 protein histidine kinase activity	IDA PMID:16753566 Cytokinins regulate a bidirectional phosphorelay network in ...	ACCEPT	Summary: AHK4 has protein histidine kinase activity (autophosphorylation and phosphotransfer to AHPs), stimulated by cytokinin binding. Reason: Histidine kinase activity of the CRE-family receptors is established biochemically (cytokinin-dependent kinase activity in yeast/E. coli and in vitro). Supporting Evidence: PMID:11479382 AHK4 expressed in budding yeast showed histidine kinase activity in a manner dependent on the presence of cytokinin PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin
GO:0004673 protein histidine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: AHK4 has protein histidine kinase activity (autophosphorylation and phosphotransfer to AHPs), stimulated by cytokinin binding. Reason: Histidine kinase activity of the CRE-family receptors is established biochemically (cytokinin-dependent kinase activity in yeast/E. coli and in vitro). Supporting Evidence: PMID:11479382 AHK4 expressed in budding yeast showed histidine kinase activity in a manner dependent on the presence of cytokinin PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin
GO:0004721 phosphoprotein phosphatase activity	IDA PMID:16753566 Cytokinins regulate a bidirectional phosphorelay network in ...	KEEP AS NON CORE	Summary: CRE1/AHK4 in its ligand-free state removes phosphate from AHP proteins (reverse phosphotransfer), decreasing the system phosphoload. Reason: Experimentally supported (IDA), but the activity is reverse phosphotransfer from phospho-His AHPs through the receptor, not a classical hydrolytic phosphoprotein phosphatase; it is a regulatory mode of the receptor rather than its core function. Unlike the IEA child GO:0004722 (removed because it specifies Ser/Thr residues, which AHK4 does not act on), this parent term is residue-agnostic and rests on the authors' own description of CRE1 as a phosphatase that dephosphorylates HPts, so it is kept rather than removed; it should not be propagated as evidence of hydrolytic phosphatase chemistry. Supporting Evidence: PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin PMID:16753566 In the absence of cytokinins, CRE1 removes phosphate from HPt proteins, decreasing the system phosphoload.
GO:0004722 protein serine/threonine phosphatase activity	IEA GO_REF:0000120	REMOVE	Summary: Electronic mapping from the UniProt EC 3.1.3.16 assignment (phosphoprotein phosphatase) to protein serine/threonine phosphatase activity. Reason: The AHK4 'phosphatase' activity acts on phospho-histidine AHPs by reverse phosphotransfer; there is no evidence that AHK4 dephosphorylates serine or threonine residues, so the EC-to-GO mapping is wrong for this protein. Supporting Evidence: PMID:16753566 In the absence of cytokinins, CRE1 removes phosphate from HPt proteins, decreasing the system phosphoload.
GO:0005515 protein binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	REMOVE	Summary: Interaction of AHK4 with the phosphotransfer protein AHP4. Reason: Generic protein binding is uninformative. The interaction is the physical basis of phosphotransfer to AHPs, which is already captured by phosphorelay sensor kinase activity (GO:0000155); GO has no specific term for binding a histidine phosphotransfer protein. Removal does not imply the interaction is false. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0005515 protein binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	REMOVE	Summary: Interaction of AHK4 with the phosphotransfer protein AHP5. Reason: Generic protein binding is uninformative. The interaction is the physical basis of phosphotransfer to AHPs, which is already captured by phosphorelay sensor kinase activity (GO:0000155); GO has no specific term for binding a histidine phosphotransfer protein. Removal does not imply the interaction is false. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0005515 protein binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	MODIFY	Summary: Interaction of AHK4 with the receptor AHK3 (yeast two-hybrid/coaffinity). Reason: Generic protein binding is uninformative; the partner is a histidine kinase, so the more specific protein histidine kinase binding term captures the reported receptor heteromerization. Proposed replacements: protein histidine kinase binding Supporting Evidence: PMID:21841169 Furthermore, membrane-bound AHK3 interacts with AHK4 in vivo.
GO:0005515 protein binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	REMOVE	Summary: Interaction of AHK4 with the phosphotransfer protein AHP3. Reason: Generic protein binding is uninformative. The interaction is the physical basis of phosphotransfer to AHPs, which is already captured by phosphorelay sensor kinase activity (GO:0000155); GO has no specific term for binding a histidine phosphotransfer protein. Removal does not imply the interaction is false. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0005515 protein binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	REMOVE	Summary: Interaction of AHK4 with the phosphotransfer protein AHP1. Reason: Generic protein binding is uninformative. The interaction is the physical basis of phosphotransfer to AHPs, which is already captured by phosphorelay sensor kinase activity (GO:0000155); GO has no specific term for binding a histidine phosphotransfer protein. Removal does not imply the interaction is false. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0005515 protein binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	REMOVE	Summary: Yeast two-hybrid interaction of AHK4 with O80452 from a medium-scale screen. Reason: Generic protein binding from a large-scale yeast two-hybrid screen is uninformative and the biological relevance of this partner to cytokinin perception is untested. Removal does not imply the interaction is false. Supporting Evidence: PMID:18642946 we conducted medium-scale yeast two-hybrid screens focusing on those members of the TCS, which are thought to be involved in cytokinin signaling
GO:0005515 protein binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	REMOVE	Summary: Yeast two-hybrid interaction of AHK4 with Q8L8Z1 from a medium-scale screen. Reason: Generic protein binding from a large-scale yeast two-hybrid screen is uninformative and the biological relevance of this partner to cytokinin perception is untested. Removal does not imply the interaction is false. Supporting Evidence: PMID:18642946 we conducted medium-scale yeast two-hybrid screens focusing on those members of the TCS, which are thought to be involved in cytokinin signaling
GO:0005515 protein binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	REMOVE	Summary: Yeast two-hybrid interaction of AHK4 with Q9SCU5 from a medium-scale screen. Reason: Generic protein binding from a large-scale yeast two-hybrid screen is uninformative and the biological relevance of this partner to cytokinin perception is untested. Removal does not imply the interaction is false. Supporting Evidence: PMID:18642946 we conducted medium-scale yeast two-hybrid screens focusing on those members of the TCS, which are thought to be involved in cytokinin signaling
GO:0005515 protein binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	REMOVE	Summary: Interaction of AHK4 with the phosphotransfer protein AHP2. Reason: Generic protein binding is uninformative. The interaction is the physical basis of phosphotransfer to AHPs, which is already captured by phosphorelay sensor kinase activity (GO:0000155); GO has no specific term for binding a histidine phosphotransfer protein. Removal does not imply the interaction is false. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0005634 nucleus	ISM GO_REF:0000122	REMOVE	Summary: Sequence-model (ISM) prediction of nuclear localization. Reason: AHK4 is an integral membrane receptor in the ER (and plasma membrane); there is no evidence for a nuclear pool, and the prediction is not supported. Supporting Evidence: PMID:21841169 cell biological and biochemical evidence for the localization of functional fluorophor-tagged fusions of Arabidopsis histidine kinase 3 (AHK3) and 4 (AHK4), members of the cytokinin receptor family, in the endoplasmic reticulum (ER) is provided
GO:0005783 endoplasmic reticulum	HDA PMID:22923678 Putative glycosyltransferases and other plant Golgi apparatu...	ACCEPT	Summary: AHK4 was detected in the ER by organelle proteomics (LOPIT). Reason: High-throughput detection consistent with targeted studies placing CRE-family receptors mainly in the ER. Supporting Evidence: PMID:21709172 Cytokinin-binding assays, fluorescent fusion proteins, and biochemical fractionation all showed that the large majority of cytokinin receptors are localized to the ER, suggesting a central role of this compartment in cytokinin signaling. PMID:21841169 cell biological and biochemical evidence for the localization of functional fluorophor-tagged fusions of Arabidopsis histidine kinase 3 (AHK3) and 4 (AHK4), members of the cytokinin receptor family, in the endoplasmic reticulum (ER) is provided
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: AHK4 is an integral membrane receptor; the bulk of cytokinin binding and receptor-fluorescent protein fusions reside in the endoplasmic reticulum membrane. Reason: ER-membrane localization of the CRE-family receptors is supported by cytokinin-binding, fluorescence and fractionation data. Supporting Evidence: PMID:21709172 Cytokinin-binding assays, fluorescent fusion proteins, and biochemical fractionation all showed that the large majority of cytokinin receptors are localized to the ER, suggesting a central role of this compartment in cytokinin signaling. PMID:21841169 cell biological and biochemical evidence for the localization of functional fluorophor-tagged fusions of Arabidopsis histidine kinase 3 (AHK3) and 4 (AHK4), members of the cytokinin receptor family, in the endoplasmic reticulum (ER) is provided
GO:0005886 plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: AHK4 was originally modelled as a plasma-membrane receptor; a minor plasma-membrane pool is reported, but most receptor protein and cytokinin binding are in the ER. Reason: Plasma membrane localization is plausible for a minor fraction but is not the principal site of the receptor; ER membrane is the better-supported location. Supporting Evidence: PMID:21709172 Cytokinin-binding assays, fluorescent fusion proteins, and biochemical fractionation all showed that the large majority of cytokinin receptors are localized to the ER, suggesting a central role of this compartment in cytokinin signaling.
GO:0005886 plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: AHK4 was originally modelled as a plasma-membrane receptor; a minor plasma-membrane pool is reported, but most receptor protein and cytokinin binding are in the ER. Reason: Plasma membrane localization is plausible for a minor fraction but is not the principal site of the receptor; ER membrane is the better-supported location. Supporting Evidence: PMID:21709172 Cytokinin-binding assays, fluorescent fusion proteins, and biochemical fractionation all showed that the large majority of cytokinin receptors are localized to the ER, suggesting a central role of this compartment in cytokinin signaling.
GO:0005886 plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: AHK4 was originally modelled as a plasma-membrane receptor; a minor plasma-membrane pool is reported, but most receptor protein and cytokinin binding are in the ER. Reason: Plasma membrane localization is plausible for a minor fraction but is not the principal site of the receptor; ER membrane is the better-supported location. Supporting Evidence: PMID:21709172 Cytokinin-binding assays, fluorescent fusion proteins, and biochemical fractionation all showed that the large majority of cytokinin receptors are localized to the ER, suggesting a central role of this compartment in cytokinin signaling.
GO:0006468 protein phosphorylation	IGI PMID:16753566 Cytokinins regulate a bidirectional phosphorelay network in ...	KEEP AS NON CORE	Summary: Genetic evidence that CRE1/AHK4 is required for phosphorylation of AHPs in planta. Reason: Correct but generic; the specific activity is histidine phosphotransfer captured by GO:0000155/GO:0004673. Supporting Evidence: PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin
GO:0006970 response to osmotic stress	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: AHK4 contributes to 'response to osmotic stress' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. This electronic/phylogenetic annotation is consistent with the experimental data. Supporting Evidence: PMID:18077346 cytokinin clearly mediates stress responses because it was required for CRE1 to function as a negative regulator of osmotic stress
GO:0007165 signal transduction	IEA GO_REF:0000002	MODIFY	Summary: Electronic annotation to the generic signal transduction term. Reason: Correct but uninformative; the specific pathway is cytokinin-activated signaling. Proposed replacements: cytokinin-activated signaling pathway Supporting Evidence: PMID:14503005 Cytokinins are perceived by three histidine kinases--CRE1/WOL/AHK4, AHK2, and AHK3--which initiate intracellular phosphotransfer.
GO:0007231 osmosensory signaling pathway	IMP PMID:22422940 Osmosensitive changes of carbohydrate metabolism in response...	KEEP AS NON CORE	Summary: AHK4 contributes to 'osmosensory signaling pathway' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:22422940 The data suggest that MCA1, CRE1, and RBOHDF-derived reactive oxygen species are involved in the regulation of osmosensitive metabolic changes.
GO:0009414 response to water deprivation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: AHK4 contributes to 'response to water deprivation' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. This electronic/phylogenetic annotation is consistent with the experimental data. Supporting Evidence: PMID:18077346 cytokinin clearly mediates stress responses because it was required for CRE1 to function as a negative regulator of osmotic stress
GO:0009414 response to water deprivation	IEP PMID:18077346 Functional analysis of AHK1/ATHK1 and cytokinin receptor his...	KEEP AS NON CORE	Summary: AHK4 contributes to 'response to water deprivation' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:18077346 cytokinin clearly mediates stress responses because it was required for CRE1 to function as a negative regulator of osmotic stress
GO:0009736 cytokinin-activated signaling pathway	TAS PMID:12068096 Two-component signal transduction pathways in Arabidopsis.	ACCEPT	Summary: AHK4 is one of three partially redundant cytokinin receptors that initiate cytokinin-activated two-component signaling. Reason: Core biological process of the receptor; triple receptor mutants are completely cytokinin-insensitive. Supporting Evidence: PMID:14503005 Cytokinins are perceived by three histidine kinases--CRE1/WOL/AHK4, AHK2, and AHK3--which initiate intracellular phosphotransfer. PMID:15166290 Plants carrying mutations in all three genes did not show cytokinin responses, including inhibition of root elongation, inhibition of root formation, cell proliferation in and greening of calli, and induction of cytokinin primary-response genes.
GO:0009884 cytokinin receptor activity	IDA PMID:16246292 A live cell hormone-binding assay on transgenic bacteria exp...	ACCEPT	Summary: AHK4 binds cytokinins with its extracytosolic CHASE domain and transduces the signal by histidine autophosphorylation. Reason: Cytokinin receptor activity is the core molecular function of the CRE-family histidine kinases. Supporting Evidence: PMID:16246292 Here we describe some biochemical features of the Arabidopsis cytokinin receptor CRE1/AHK4 expressed in Escherichia coli PMID:21964459 Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor
GO:0009884 cytokinin receptor activity	IEA GO_REF:0000117	ACCEPT	Summary: AHK4 binds cytokinins with its extracytosolic CHASE domain and transduces the signal by histidine autophosphorylation. Reason: Cytokinin receptor activity is the core molecular function of the CRE-family histidine kinases. Supporting Evidence: PMID:11234017 CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor PMID:11230563 evidence is presented showing that the AHK4 His-kinase has an ability to serve as a cytokinin-responsive environmental sensor PMID:21964459 Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor
GO:0009884 cytokinin receptor activity	TAS PMID:14503005 Perception and signal transduction of cytokinins.	ACCEPT	Summary: AHK4 binds cytokinins with its extracytosolic CHASE domain and transduces the signal by histidine autophosphorylation. Reason: Cytokinin receptor activity is the core molecular function of the CRE-family histidine kinases. Supporting Evidence: PMID:11234017 CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor PMID:11230563 evidence is presented showing that the AHK4 His-kinase has an ability to serve as a cytokinin-responsive environmental sensor PMID:21964459 Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor
GO:0009884 cytokinin receptor activity	TAS PMID:16361392 Arabidopsis cytokinin receptor mutants reveal functions in s...	ACCEPT	Summary: AHK4 binds cytokinins with its extracytosolic CHASE domain and transduces the signal by histidine autophosphorylation. Reason: Cytokinin receptor activity is the core molecular function of the CRE-family histidine kinases. Supporting Evidence: PMID:11234017 CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor PMID:11230563 evidence is presented showing that the AHK4 His-kinase has an ability to serve as a cytokinin-responsive environmental sensor PMID:21964459 Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor
GO:0009885 transmembrane histidine kinase cytokinin receptor activity	IDA PMID:11230563 The Arabidopsis sensor His-kinase, AHk4, can respond to cyto...	ACCEPT	Summary: AHK4 binds cytokinins with its extracytosolic CHASE domain and transduces the signal by histidine autophosphorylation. Reason: Cytokinin receptor activity is the core molecular function of the CRE-family histidine kinases. Supporting Evidence: PMID:11234017 CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor PMID:11230563 evidence is presented showing that the AHK4 His-kinase has an ability to serve as a cytokinin-responsive environmental sensor PMID:21964459 Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor
GO:0010029 regulation of seed germination	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of seed germination' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. This electronic/phylogenetic annotation is consistent with the experimental data. Supporting Evidence: PMID:16361392 Mutant seeds had more rapid germination, reduced requirement for light, and decreased far-red light sensitivity, unraveling cytokinin functions in seed germination control.
GO:0010029 regulation of seed germination	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of seed germination' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. This electronic/phylogenetic annotation is consistent with the experimental data. Supporting Evidence: PMID:16361392 Mutant seeds had more rapid germination, reduced requirement for light, and decreased far-red light sensitivity, unraveling cytokinin functions in seed germination control.
GO:0010029 regulation of seed germination	IMP PMID:16361392 Arabidopsis cytokinin receptor mutants reveal functions in s...	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of seed germination' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:16361392 Mutant seeds had more rapid germination, reduced requirement for light, and decreased far-red light sensitivity, unraveling cytokinin functions in seed germination control.
GO:0010086 embryonic root morphogenesis	IMP PMID:11114883 A novel two-component hybrid molecule regulates vascular mor...	KEEP AS NON CORE	Summary: AHK4 contributes to 'embryonic root morphogenesis' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:11114883 These divisions require the WOODEN LEG (WOL) gene.
GO:0010150 leaf senescence	IMP NOT PMID:16407152 Cytokinin-mediated control of leaf longevity by AHK3 through...	ACCEPT	Summary: NOT annotation: loss of AHK4 did not affect cytokinin-dependent delay of leaf senescence, unlike loss of AHK3. Reason: The abstract explicitly states that a loss-of-function mutation in AHK3, but not the other receptors, reduced cytokinin control of leaf senescence. Supporting Evidence: PMID:16407152 A loss-of-function mutation in AHK3, but not of the other cytokinin receptors, conferred a reduced sensitivity to cytokinin in cytokinin-dependent delay of leaf senescence and abolished cytokinin-dependent phosphorylation of ARR2.
GO:0016036 cellular response to phosphate starvation	IMP PMID:15923327 Interaction between phosphate-starvation, sugar, and cytokin...	KEEP AS NON CORE	Summary: AHK4 contributes to 'cellular response to phosphate starvation' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:15923327 These effects of the ahk3 mutation were especially evident in combination with the cre1 mutation, indicating partial functional redundancy between these receptors. PMID:15923327 in the case of Pi starvation-responsive genes, the effect of ahk3 , although not so important as that of cre1 , was evident
GO:0016772 transferase activity, transferring phosphorus-containing groups	IEA GO_REF:0000002	MODIFY	Summary: Electronic annotation to a very general transferase term. Reason: Correct but uninformative; the specific activity is phosphorelay sensor kinase activity. Proposed replacements: phosphorelay sensor kinase activity Supporting Evidence: PMID:16753566 CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin
GO:0019899 enzyme binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	KEEP AS NON CORE	Summary: Yeast two-hybrid interaction of AHK4 with a non-two-component enzyme/kinase identified in a medium-scale interaction screen. Reason: Experimental but from a large-scale Y2H screen without functional follow-up; the interaction is not part of the established receptor mechanism. Retained as non-core pending validation. Supporting Evidence: PMID:18642946 we conducted medium-scale yeast two-hybrid screens focusing on those members of the TCS, which are thought to be involved in cytokinin signaling
GO:0019901 protein kinase binding	IPI PMID:18642946 Toward an interaction map of the two-component signaling pat...	KEEP AS NON CORE	Summary: Yeast two-hybrid interaction of AHK4 with a non-two-component enzyme/kinase identified in a medium-scale interaction screen. Reason: Experimental but from a large-scale Y2H screen without functional follow-up; the interaction is not part of the established receptor mechanism. Retained as non-core pending validation. Supporting Evidence: PMID:18642946 we conducted medium-scale yeast two-hybrid screens focusing on those members of the TCS, which are thought to be involved in cytokinin signaling
GO:0033500 carbohydrate homeostasis	IMP PMID:22422940 Osmosensitive changes of carbohydrate metabolism in response...	KEEP AS NON CORE	Summary: AHK4 contributes to 'carbohydrate homeostasis' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:22422940 The data suggest that MCA1, CRE1, and RBOHDF-derived reactive oxygen species are involved in the regulation of osmosensitive metabolic changes.
GO:0033554 cellular response to stress	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very general ARBA-derived electronic process annotation. Reason: Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. Supporting Evidence: PMID:15166290 Plants carrying mutations in all three genes did not show cytokinin responses, including inhibition of root elongation, inhibition of root formation, cell proliferation in and greening of calli, and induction of cytokinin primary-response genes.
GO:0042742 defense response to bacterium	IDA PMID:19129491 Identification of Rhodococcus fascians cytokinins and their ...	MARK AS OVER ANNOTATED	Summary: AHK3 and AHK4 are required for the leafy-gall symptoms caused by the cytokinin-producing pathogen Rhodococcus fascians. Reason: The receptors are hijacked by bacterial cytokinins to cause disease symptoms; this is host susceptibility, not a defense response by the plant. Supporting Evidence: PMID:19129491 We show that the CK receptors AHK3 and AHK4 of Arabidopsis thaliana are essential for symptom development, and that the CK perception machinery is induced upon infection
GO:0042742 defense response to bacterium	IMP PMID:19129491 Identification of Rhodococcus fascians cytokinins and their ...	MARK AS OVER ANNOTATED	Summary: AHK3 and AHK4 are required for the leafy-gall symptoms caused by the cytokinin-producing pathogen Rhodococcus fascians. Reason: The receptors are hijacked by bacterial cytokinins to cause disease symptoms; this is host susceptibility, not a defense response by the plant. Supporting Evidence: PMID:19129491 We show that the CK receptors AHK3 and AHK4 of Arabidopsis thaliana are essential for symptom development, and that the CK perception machinery is induced upon infection
GO:0043424 protein histidine kinase binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA-rule electronic annotation for binding to other histidine kinases. Reason: Consistent with experimentally reported heteromeric interactions among CRE-family receptors; retained as non-core. Supporting Evidence: PMID:16965536 An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion.
GO:0043424 protein histidine kinase binding	IPI PMID:16965536 Analysis of protein interactions within the cytokinin-signal...	KEEP AS NON CORE	Summary: AHK4 interacts with other CRE-family receptor histidine kinases. Reason: Receptor homo/heteromerization is experimentally supported (Y2H, coaffinity, in vivo FRET for AHK3-AHK4) but is a structural property rather than the signalling activity itself. Supporting Evidence: PMID:21841169 Furthermore, membrane-bound AHK3 interacts with AHK4 in vivo.
GO:0048509 regulation of meristem development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of meristem development' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. This electronic/phylogenetic annotation is consistent with the experimental data. Supporting Evidence: PMID:20110319 Loss of cytokinin perception leads to a complete failure of meristem establishment and growth arrest after germination.
GO:0048509 regulation of meristem development	IMP PMID:20110319 STIMPY mediates cytokinin signaling during shoot meristem es...	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of meristem development' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:20110319 Loss of cytokinin perception leads to a complete failure of meristem establishment and growth arrest after germination.
GO:0048831 regulation of shoot system development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of shoot system development' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: A pleiotropic output of cytokinin signaling rather than the receptor's core function. The cached abstract of PMID:16361392 (abstract-only) assays cre1/ahk4 alongside ahk2 and ahk3 but attributes the prominent shoot-growth role to the AHK2/AHK3 combination; any CRE1/AHK4-specific contribution is in the full text, not available in the cache, so we defer to the curator of the matching IMP row. This electronic annotation is consistent with that IMP. Supporting Evidence: PMID:16361392 We used loss-of-function mutants to study three Arabidopsis thaliana sensor histidine kinases, AHK2, AHK3, and CRE1/AHK4, known to be cytokinin receptors. PMID:16361392 Together, the analyses reveal partially redundant functions of the cytokinin receptors
GO:0048831 regulation of shoot system development	IMP PMID:16361392 Arabidopsis cytokinin receptor mutants reveal functions in s...	KEEP AS NON CORE	Summary: AHK4 contributes to 'regulation of shoot system development' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: A pleiotropic output of cytokinin signaling rather than the receptor's core function. The cached abstract (abstract-only) assays cre1/ahk4 alongside ahk2 and ahk3 but attributes the prominent shoot-growth role to the AHK2/AHK3 combination; the CRE1/AHK4-specific data behind this IMP are in the full text, not available in the cache, so we defer to the curator who read it. Supporting Evidence: PMID:16361392 We used loss-of-function mutants to study three Arabidopsis thaliana sensor histidine kinases, AHK2, AHK3, and CRE1/AHK4, known to be cytokinin receptors. PMID:16361392 Together, the analyses reveal partially redundant functions of the cytokinin receptors
GO:0070417 cellular response to cold	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic transfer of cellular response to cold from the CRE-family clade. Reason: Plausible as an inherited clade property, but experimental evidence implicates AHK2 and AHK3 more strongly than CRE1/AHK4 in cold-induced type-A ARR expression; peripheral, non-core role. Supporting Evidence: PMID:20463025 AHK2 and AHK3 were found to be primarily involved in mediating cold to express A-type ARRs despite cytokinin deficiency.
GO:0071329 cellular response to sucrose stimulus	IMP PMID:15923327 Interaction between phosphate-starvation, sugar, and cytokin...	KEEP AS NON CORE	Summary: AHK4 contributes to 'cellular response to sucrose stimulus' as one of the downstream physiological/developmental outputs of cytokinin perception. Reason: Supported by mutant or expression data, but this is a pleiotropic output of cytokinin signaling rather than the receptor's core function. Supporting Evidence: PMID:15923327 Our studies have shown that plants with impaired cytokinin receptors CRE1 and AHK3 display increased sugar sensitivity in seedling survival tests
GO:0160109 plant gross anatomical part developmental process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very general ARBA-derived electronic process annotation. Reason: Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. Supporting Evidence: PMID:15166290 Plants carrying mutations in all three genes did not show cytokinin responses, including inhibition of root elongation, inhibition of root formation, cell proliferation in and greening of calli, and induction of cytokinin primary-response genes.
GO:1901701 cellular response to oxygen-containing compound	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very general ARBA-derived electronic process annotation. Reason: Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. Supporting Evidence: PMID:15166290 Plants carrying mutations in all three genes did not show cytokinin responses, including inhibition of root elongation, inhibition of root formation, cell proliferation in and greening of calli, and induction of cytokinin primary-response genes.
GO:1902358 sulfate transmembrane transport	IMP PMID:15144379 A novel regulatory pathway of sulfate uptake in Arabidopsis ...	MARK AS OVER ANNOTATED	Summary: CRE1/AHK4 is required for cytokinin-mediated repression of high-affinity sulfate transporter genes in roots. Reason: AHK4 does not transport sulfate; it negatively regulates sulfate transporter expression, an indirect downstream effect of cytokinin signaling. No GO term for negative regulation of sulfate transmembrane transport exists. Supporting Evidence: PMID:15144379 The effect of cytokinin on sulfate uptake was moderated in the cre1-1 mutant, providing genetic evidence for involvement of CRE1/WOL/AHK4 in the negative regulation of high-affinity sulfate transporters.

Gene Description

Existing Annotations Review

Core Functions

References

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