dhkA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that DhkA acts at the plasma membrane is consistent with direct experimental evidence that DhkA is a membrane-spanning receptor histidine kinase. Reason: DhkA is a multi-pass membrane protein with an extracellular ligand-binding loop and a cytoplasmic catalytic domain, directly demonstrated by epitope-tagging topology experiments. Plasma membrane localization is well supported. Supporting Evidence: PMID:10373524 The results presented here show that DhkA is a membrane-spanning histidine kinase and is likely to be a receptor which mediates the cellular response to SDF-2 in the genetic pathway that eventually leads to PKA-dependent differentiation.
GO:0000155 phosphorelay sensor kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of phosphorelay sensor kinase activity is strongly corroborated by direct biochemical and genetic evidence for DhkA histidine autophosphorylation and phosphorelay. Reason: DhkA autophosphorylates on His1395 and relays phosphate to Asp2075 and onward to RdeA/RegA, the defining activity of a phosphorelay sensor kinase. Supporting Evidence: PMID:10373524 DhkA is a protein kinase able to autophosphorylate on a histidine residue
GO:0000160 phosphorelay signal transduction system	IBA GO_REF:0000033	ACCEPT	Summary: DhkA operates within a two-component phosphorelay signal transduction system, transferring phosphate from its histidine through RdeA to the RegA response regulator. Reason: Directly supported by both biochemical and genetic evidence for a His-to-Asp phosphorelay linking DhkA to RdeA and RegA. Supporting Evidence: PMID:15897458 The SDF-2 receptor in Dictyostelium is a membrane-associated histidine kinase, DhkA, that relays phosphate via a histidine in RdeA to response regulator regions on several proteins
GO:0000155 phosphorelay sensor kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic inference of phosphorelay sensor kinase activity from InterPro histidine-kinase domains agrees with experimentally demonstrated activity. Reason: Redundant with the experimentally supported IMP/IBA annotations to the same term; the domain-based inference is correct. Supporting Evidence: PMID:10373524 DhkA is a protein kinase able to autophosphorylate on a histidine residue
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO inference from the response-regulator receiver domain that DhkA participates in a phosphorelay signal transduction system. Reason: Correct and redundant with the experimentally supported IBA annotation to the same term. Supporting Evidence: PMID:15897458 The SDF-2 receptor in Dictyostelium is a membrane-associated histidine kinase, DhkA, that relays phosphate via a histidine in RdeA to response regulator regions on several proteins
GO:0004673 protein histidine kinase activity	IEA GO_REF:0000003	KEEP AS NON CORE	Summary: EC-based inference (EC 2.7.13.3) of protein histidine kinase activity. DhkA autophosphorylates on a histidine, consistent with this activity, though the more specific phosphorelay sensor kinase term better captures its two-component function. Reason: The activity is correct (His autophosphorylation) but this general protein histidine kinase term is largely subsumed by the more informative phosphorelay sensor kinase activity (GO:0000155) and transmembrane receptor histidine kinase activity (GO:0009784) annotations that represent the core function. Supporting Evidence: PMID:10373524 Site-directed mutagenesis of histidine 1395 to glutamine in the catalytic domain blocked autophosphorylation.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic inference of plasma membrane localization from the UniProt subcellular location, consistent with the direct experimental evidence. Reason: Redundant with the experimentally supported IDA annotation to plasma membrane; DhkA is a multi-pass plasma membrane protein. Supporting Evidence: PMID:10373524 The results presented here show that DhkA is a membrane-spanning histidine kinase and is likely to be a receptor which mediates the cellular response to SDF-2 in the genetic pathway that eventually leads to PKA-dependent differentiation.
GO:0007165 signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: General signal transduction inference from InterPro. Correct but far less informative than the specific phosphorelay signal transduction system annotation. Reason: This is a high-level parent of the more specific and experimentally supported phosphorelay signal transduction system (GO:0000160) annotation and adds little information on its own. Supporting Evidence: PMID:15897458 The SDF-2 receptor in Dictyostelium is a membrane-associated histidine kinase, DhkA, that relays phosphate via a histidine in RdeA to response regulator regions on several proteins
GO:0016772 transferase activity, transferring phosphorus-containing groups	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Very general molecular function parent inferred from InterPro. Correct (kinase transfers phosphate) but uninformative relative to the specific histidine kinase annotations. Reason: This broad grouping term is a distant parent of the specific and experimentally supported kinase activities already annotated; it does not represent the core function on its own. Supporting Evidence: PMID:10373524 DhkA is a protein kinase able to autophosphorylate on a histidine residue
GO:0009784 transmembrane receptor histidine kinase activity	IMP PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	ACCEPT	Summary: Core molecular function. DhkA is a membrane-spanning receptor histidine kinase whose extracellular loop binds the SDF-2 signal and whose cytoplasmic catalytic domain autophosphorylates on His1395; mutation of His1395 abolishes activity and function. Reason: Directly supported by topology mapping (extracellular ligand loop, cytoplasmic catalytic domain), in vitro autophosphorylation, and mutagenesis of the essential catalytic histidine. Supporting Evidence: PMID:10373524 The results presented here show that DhkA is a membrane-spanning histidine kinase and is likely to be a receptor which mediates the cellular response to SDF-2 in the genetic pathway that eventually leads to PKA-dependent differentiation. PMID:10373524 Thus, the 310-amino-acid loop between the transmembrane domains of DhkA is exposed to the intercellular medium and appears to be critical for ligand binding and activation of DhkA.
GO:0005886 plasma membrane	IDA PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	ACCEPT	Summary: Direct experimental evidence places DhkA in the plasma membrane, with an extracellular ligand-binding loop and a cytoplasmic catalytic domain established by epitope-tag protease-protection topology mapping. Reason: Core cellular location, directly demonstrated. DhkA is a bona fide membrane-spanning receptor. Supporting Evidence: PMID:10373524 By inserting MYC 6 epitopes into DhkA, we were able to show that the loop is extracellular while the catalytic domain is cytoplasmic.
GO:0009897 external side of plasma membrane	IDA PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	ACCEPT	Summary: The 310-amino-acid ligand-binding loop of DhkA between its two transmembrane domains is exposed on the external side of the plasma membrane, demonstrated by protease-protection experiments. Reason: Directly supported topology; the SDF-2-binding loop faces the extracellular (intercellular) medium. Supporting Evidence: PMID:10373524 Thus, the 310-amino-acid loop between the transmembrane domains of DhkA is exposed to the intercellular medium and appears to be critical for ligand binding and activation of DhkA.
GO:0009898 cytoplasmic side of plasma membrane	IDA PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	ACCEPT	Summary: The catalytic histidine kinase and receiver domains of DhkA face the cytoplasmic side of the plasma membrane, where the relay aspartate can act on its downstream response regulator. Reason: Directly supported topology; the C-terminal catalytic portion is internal/cytoplasmic. Supporting Evidence: PMID:10373524 The carboxy-terminal portion of DhkA that carries the conserved aspartate to which the phosphate is relayed appears to be internal, where it can affect its response regulator.
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:12796307 Genetic interactions of the E3 ubiquitin ligase component Fb...	MARK AS OVER ANNOTATED	Summary: This annotation captures the finding that disruption of dhkA strongly lowers intracellular cAMP levels, connecting DhkA to cAMP metabolism. However, the specific term describes the cell-surface cAMP GPCR (cAR)-driven pathway that activates adenylate cyclase during aggregation, which is a poor fit for DhkA. DhkA is a histidine kinase that acts on intracellular cAMP through the RdeA/RegA phosphodiesterase and PKA during culmination, not a G protein-coupled cAMP receptor pathway. Reason: The underlying genetic evidence (dhkA mutants have severalfold reduced cAMP) is real, but the chosen term denotes the GPCR/adenylate-cyclase aggregation pathway rather than the intracellular RegA/PKA phosphorelay pathway in which DhkA actually acts. The term over-specifies an inappropriate pathway; the DhkA cAMP connection is better represented by its phosphorelay and sporulation annotations. Supporting Evidence: PMID:12796307 The levels of cAMP are relatively constant during multicellular development in all strains except the dhkA mutant, in which it is reduced at least sixfold.
GO:0009784 transmembrane receptor histidine kinase activity	IDA PMID:15897458 Peptide signaling during terminal differentiation of Dictyos...	ACCEPT	Summary: Core molecular function, independently supported. Using a yeast reconstitution system, DhkA functions as a constitutive histidine kinase whose phosphorelay activity is inhibited upon binding its SDF-2 ligand. Reason: Direct functional demonstration that DhkA is a ligand-regulated receptor histidine kinase; SDF-2 binding inhibits its phosphorelay activity. Supporting Evidence: PMID:15897458 Using a yeast system we show that ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation. PMID:15897458 It appears that DhkA functions as a constitutive kinase in yeast that is inhibited upon ligand binding.
GO:0000155 phosphorelay sensor kinase activity	IMP PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	ACCEPT	Summary: Core molecular function. Genetic and biochemical evidence show DhkA autophosphorylates on His1395 and relays phosphate to the receiver aspartate Asp2075; both residues are required for function. Reason: Mutation of His1395 blocks autophosphorylation and mutation of Asp2075 compromises function, directly establishing DhkA as a phosphorelay sensor kinase. Supporting Evidence: PMID:10373524 Site-directed mutagenesis of histidine 1395 to glutamine in the catalytic domain blocked autophosphorylation. PMID:10373524 DhkA is a protein kinase able to autophosphorylate on a histidine residue
GO:0031288 sorocarp morphogenesis	IGI PMID:10373524 SDF-2 induction of terminal differentiation in Dictyostelium...	KEEP AS NON CORE	Summary: DhkA acts within the signaling pathway that shapes the fruiting body (sorocarp) during culmination; genetic interaction with a downstream kinase (DhkB) supports its role in morphogenesis, though this is a developmental consequence rather than the core molecular activity. Reason: The role in sorocarp morphogenesis is a valid developmental output of DhkA phosphorelay signaling but is downstream of and secondary to its core receptor histidine kinase function. Supporting Evidence: PMID:10373524 The results presented here show that DhkA is a membrane-spanning histidine kinase and is likely to be a receptor which mediates the cellular response to SDF-2 in the genetic pathway that eventually leads to PKA-dependent differentiation.
GO:0030587 sorocarp development	HMP PMID:17659086 High-throughput analysis of spatio-temporal dynamics in Dict...	KEEP AS NON CORE	Summary: High-throughput mutant phenotyping shows dhkA insertion mutants have defects specific to the slug-to-culmination stage, including the characteristic long-stalk phenotype, consistent with a role in sorocarp development. Reason: Well-supported developmental role, but this whole-organism developmental process is a downstream consequence of DhkA's core signaling function rather than the molecular activity itself. Supporting Evidence: PMID:17659086 In contrast, dhkA and acrA show mutant phenotypes only at later stages consistent with their specific roles during slug to culmination stage. PMID:17659086 long stalks in dhkA [28] also agree well with known mutant phenotypes
GO:0030435 sporulation resulting in formation of a cellular spore	IMP PMID:12796307 Genetic interactions of the E3 ubiquitin ligase component Fb...	ACCEPT	Summary: DhkA controls spore encapsulation. Disruption of dhkA suppresses the excessive sporulation of fbxA mutants and dhkA mutants are impaired in sporulation, linking DhkA to the control of spore formation via the RegA/cAMP/PKA pathway. Reason: DhkA is a central controller of the timing of prespore-cell encapsulation into spores; multiple independent studies place it upstream of sporulation. Supporting Evidence: PMID:12796307 Studies of dhk A indicate that it is important at late stages of development, when the prespore cells encapsulate.
GO:0030587 sorocarp development	IMP PMID:12796307 Genetic interactions of the E3 ubiquitin ligase component Fb...	KEEP AS NON CORE	Summary: dhkA mutation modifies fruiting-body development and rescues the culmination deficiency of fbxA mutants, consistent with a role in sorocarp development. Reason: Valid developmental role downstream of the core phosphorelay signaling function; secondary to the molecular activity. Supporting Evidence: PMID:12796307 Studies of dhk A indicate that it is important at late stages of development, when the prespore cells encapsulate.
GO:0030435 sporulation resulting in formation of a cellular spore	IMP PMID:8670894 A two-component histidine kinase gene that functions in Dict...	ACCEPT	Summary: The original dhkA mutant characterization showed DhkA functions in the control of terminal differentiation of prespore cells, i.e. sporulation. Reason: Foundational genetic evidence that DhkA controls the terminal differentiation (encapsulation) of prespore cells into spores. Supporting Evidence: PMID:8670894 In Dictyostelium, we found that DhkA functions both in the regulation of prestalk gene expression and in the control of the terminal differentiation of prespore cells.
GO:0031150 sorocarp stalk development	IMP PMID:8670894 A two-component histidine kinase gene that functions in Dict...	KEEP AS NON CORE	Summary: DhkA functions in the regulation of prestalk gene expression, and dhkA mutants show stalk defects (including long stalks), supporting a role in stalk (sorocarp stalk) development. Reason: Regulation of prestalk gene expression and stalk morphology is a developmental output of DhkA signaling, secondary to its core molecular function. Supporting Evidence: PMID:8670894 In Dictyostelium, we found that DhkA functions both in the regulation of prestalk gene expression and in the control of the terminal differentiation of prespore cells.
GO:0005524 ATP binding	TAS PMID:9191038 Histidine kinases in signal transduction pathways of eukaryo...	ACCEPT	Summary: DhkA binds ATP as the phosphoryl donor for histidine autophosphorylation, the defining activity of autophosphorylating histidine kinases. Reason: ATP binding is required for and directly evidenced by the ATP-dependent histidine autophosphorylation of the DhkA catalytic domain. Supporting Evidence: PMID:10373524 incorporation of labelled phosphate from ATP consistent with histidine autophosphorylation PMID:9191038 A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development.

Gene Description

Existing Annotations Review

Core Functions

DhkA operates as a phosphorelay sensor kinase, relaying phosphate from its autophosphorylated His1395 to the receiver aspartate Asp2075 and onward via RdeA to the RegA response regulator, thereby controlling intracellular cAMP and PKA activity that trigger spore encapsulation.

References

Suggested Experiments

📄 View Raw YAML