yakA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of Ser/Thr kinase activity is consistent with YakA being an active member of the CMGC/DYRK kinase family. DYRK-family kinases phosphorylate their substrates on serine/threonine residues, and purified YakA phosphorylates myelin basic protein in vitro. Reason: YakA has a canonical protein kinase domain with intact catalytic residues and demonstrated in vitro kinase activity; Ser/Thr-directed catalysis is the substrate-directed activity of DYRK-family kinases and represents a core molecular function. Supporting Evidence: PMID:9584128 Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasmic localization is supported by direct evidence; YakA-GFP was localized to the cytosol. Reason: Direct localization of YakA-GFP to the cytosol confirms the phylogenetic inference of cytoplasmic activity. Supporting Evidence: PMID:11410593 We localized YakA-GFP to the cytosol suggesting that YakA may be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3
GO:0004713 protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT tyrosine kinase inference is compatible with YakA membership in the dual-specificity DYRK family. Tyrosine autophosphorylation satisfies the annotated catalytic activity. Reason: PTHR24058-paint.tsv places GO:0004713 at the eukaryotic ancestral node PTN000624409, with plant and yeast experimental descendants. QuickGO defines the reaction as phosphorylation of a protein tyrosine, without requiring a distinct substrate protein or excluding cis autophosphorylation. No YakA-specific catalytic loss was established. The former rejection imposed an unsupported trans-only restriction and conflicted with the accepted dual-specificity kinase annotation. Retain the inherited activity while distinguishing family inference from direct YakA residue-specific assays. Supporting Evidence: PMID:11410593 a subclass of dual-specificity Yak-related kinases (Dyrk) with unknown function
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: The general kinase annotation correctly describes the experimentally demonstrated catalytic activity of YakA. Reason: Purified YakA phosphorylates myelin basic protein. Its more specific dual-specificity and serine/threonine kinase annotations add detail, but do not make the parent kinase activity non-core; retain consistently with the direct IDA annotation. Supporting Evidence: PMID:9584128 Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein
GO:0004712 protein serine/threonine/tyrosine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: This dual-specificity kinase term is the most appropriate molecular function for a DYRK/MNB-subfamily kinase, capturing both activation-loop tyrosine autophosphorylation and Ser/Thr-directed substrate phosphorylation. Reason: YakA belongs to the MNB/DYRK subfamily of dual-specificity kinases; this EC-derived term (EC 2.7.12.1) accurately represents its catalytic activity and is the best single molecular-function descriptor. Supporting Evidence: PMID:11410593 YakA may be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3, a subclass of dual-specificity Yak-related kinases (Dyrk) with unknown function
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Tyrosine kinase activity is compatible with the dual-specificity YakA catalytic assignment, including activation-loop autophosphorylation. Reason: The GO:0004713 reaction does not exclude autophosphorylation or require an external protein substrate. Consequently the Rhea-derived activity is not invalidated by the DYRK activation mechanism. Retain the electronic inference without asserting that tyrosine phosphorylation of other proteins has been demonstrated for YakA. Supporting Evidence: PMID:11410593 a subclass of dual-specificity Yak-related kinases (Dyrk) with unknown function
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding is expected for an active protein kinase; the UniProt record annotates an ATP-binding site and a glycine-rich P-loop in the kinase domain. Reason: ATP binding is a necessary supporting activity for catalysis but is not itself the distinguishing core function; it is retained as a non-core molecular-function annotation. Supporting Evidence: PMID:9584128 Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to cytoplasm, consistent with the direct YakA-GFP cytosolic localization. Reason: Cytoplasmic/cytosolic localization is directly established for YakA, so this electronic annotation is correct. Supporting Evidence: PMID:11410593 We localized YakA-GFP to the cytosol
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Rhea-derived serine kinase activity, a subtype of the Ser/Thr kinase activity that is consistent with DYRK-family substrate specificity. Reason: Serine kinase activity is a correct subtype of YakA's catalytic function but is subsumed by the more complete serine/threonine/tyrosine dual-specificity description. Supporting Evidence: PMID:9584128 Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein
GO:0005737 cytoplasm	IDA PMID:11410593 The protein kinase YakA regulates g-protein-linked signaling...	ACCEPT	Summary: Direct experimental localization of YakA-GFP to the cytosol establishes the cytoplasm as the site of YakA activity. Reason: This IDA annotation is the primary evidence for YakA's cytoplasmic localization and represents its core cellular location. Supporting Evidence: PMID:11410593 We localized YakA-GFP to the cytosol
GO:0008277 regulation of G protein-coupled receptor signaling pathway	IMP PMID:11410593 The protein kinase YakA regulates g-protein-linked signaling...	KEEP AS NON CORE	Summary: yakA-null cells were isolated in a screen for mutants resembling G-protein beta-subunit nulls and show strong defects in folic acid-induced (G-protein-coupled) responses, placing YakA in G-protein-mediated signaling. Reason: YakA modulates G-protein-linked chemotactic signaling responses, but this is a downstream/regulatory role rather than the kinase's core catalytic function; the experimental (IMP) evidence supports involvement. Supporting Evidence: PMID:11410593 The yakA-null cells have strong defects in folic acid-induced responses, such as actin polymerization and cGMP accumulation, indicating that they play a role in G-protein-mediated signaling responses
GO:0010468 regulation of gene expression	IMP PMID:10375515 Starvation promotes Dictyostelium development by relieving P...	ACCEPT	Summary: YakA governs the growth-to-development transition by reprogramming transcription, repressing growth-phase genes and inducing developmental genes. This regulation of gene expression is a core biological role. Reason: Multiple mutant studies show YakA is required for the starvation-induced changes in gene expression (down-regulation of vegetative genes such as pufA and cprD, induction of developmental/cAMP-signaling genes). This is a central function of the kinase. Supporting Evidence: PMID:10375515 The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes
GO:0010628 positive regulation of gene expression	IMP PMID:24373846 Glutathione initiates the development of Dictyostelium disco...	ACCEPT	Summary: YakA induces the expression of early developmental genes, including PKA-C, the adenylyl cyclase ACA and the cAMP receptor cAR1, that are required to initiate development. Reason: YakA is required for the up-regulation of key developmental genes upon starvation; constitutive YakA expression restores their induction, supporting a positive regulatory role in gene expression. Supporting Evidence: PMID:24373846 the expression of yakA, which initiates development and induces the expression of PKA-C, ACA, and cAR1, was regulated by the intracellular concentration of GSH
GO:0010628 positive regulation of gene expression	IMP PMID:9584128 YakA, a protein kinase required for the transition from grow...	ACCEPT	Summary: yakA-null cells fail to induce genes required for the earliest stages of development, and conditional YakA expression promotes expression of cAMP signaling genes, demonstrating positive regulation of developmental gene expression. Reason: Loss-of-function and gain-of-function evidence both show YakA is needed to switch on developmental gene expression, a core aspect of its function. Supporting Evidence: PMID:9584128 Expression of yakA from a conditional promoter causes cell-cycle arrest in nutrient-rich medium and promotes developmental events, such as the expression of genes required for cAMP signaling
GO:0010629 negative regulation of gene expression	IMP PMID:24373846 Glutathione initiates the development of Dictyostelium disco...	ACCEPT	Summary: YakA is required for the starvation-induced decrease of vegetative gene expression, in particular the down-regulation of the pufA transcript, so it also negatively regulates gene expression. Reason: YakA represses growth-phase/vegetative genes as part of the growth-to- development switch; the requirement of YakA for decreasing pufA and other vegetative mRNAs supports a negative regulatory role. Supporting Evidence: PMID:12134067 YakA is necessary for the decrease in vegetative gene expression that occurs when cells are starved and in particular, for the decrease in the mRNA levels for the pufA gene
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:20670432 KeaA, a Dictyostelium Kelch-domain protein that regulates th...	ACCEPT	Summary: By up-regulating pkaC, the adenylyl cyclase acaA and the cAMP receptor carA, YakA acts upstream of the aggregation-stage cAMP relay that couples the cAMP receptor to adenylyl cyclase activation. Reason: YakA is an effector of the gene expression changes that enable cAMP production and detection during aggregation, placing it upstream of the adenylate cyclase-activating cAMP receptor signaling pathway. Supporting Evidence: PMID:20670432 YakA is an effector of the gene expression changes that follow starvation including the down-regulation of vegetative genes, the up-regulation of the cAMP-dependent protein kinase, pkaC, the adenylyl cyclase acaA, and the cAMP receptor carA
GO:0010225 response to UV-C	IDA PMID:25858552 Response of Dictyostelium discoideum to UV-C and involvement...	KEEP AS NON CORE	Summary: UV-C irradiation alters yakA expression as part of the developmental response, and yakA is grouped with genes crucial for cell-cycle exit and the growth-to-differentiation transition affected by UV-C. Reason: This annotation reflects that yakA expression is modulated during the UV-C response rather than a dedicated UV-C function; it is a peripheral, non-core biological-process association. Supporting Evidence: PMID:25858552 failed to affect expression of car1, aca, yakA, crucial for regulating cell cycle exit and growth to differentiation transition
GO:0006979 response to oxidative stress	IMP PMID:12134067 Role for YakA, cAMP, and protein kinase A in regulation of s...	ACCEPT	Summary: yakA-null cells are hypersensitive to oxidative stress (hydrogen peroxide), and a second-site pkaC mutation suppresses this sensitivity, identifying YakA as a component of the oxidative-stress growth-arrest pathway. Reason: Strong mutant evidence shows YakA is required for survival of and growth arrest in response to oxidative stress via cAMP/PKA; this is a well-supported biological role. Supporting Evidence: PMID:12134067 yakA null cells are hypersensitive to nitrosoative/oxidative stress and that a second-site mutation in pkaC suppresses this sensitivity
GO:0051409 response to nitrosative stress	IMP PMID:12134067 Role for YakA, cAMP, and protein kinase A in regulation of s...	ACCEPT	Summary: yakA-null cells are hypersensitive to nitrosative stress (sodium nitroprusside), and this hypersensitivity is suppressed by loss of pkaC, implicating YakA in the nitrosative-stress response. Reason: Mutant phenotype evidence directly supports a required role for YakA in survival under nitrosative stress through the cAMP/PKA pathway. Supporting Evidence: PMID:12134067 yakA null cells are hypersensitive to nitrosoative/oxidative stress and that a second-site mutation in pkaC suppresses this sensitivity
GO:0004672 protein kinase activity	IDA PMID:9584128 YakA, a protein kinase required for the transition from grow...	ACCEPT	Summary: Direct in vitro assay shows purified YakA phosphorylates myelin basic protein, providing experimental evidence of protein kinase activity. Reason: This IDA is the direct experimental basis for YakA's protein kinase activity; it is core, although the specific Ser/Thr/Tyr dual-specificity term is a more precise descriptor. Supporting Evidence: PMID:9584128 Purified YakA expressed in E. coli is able to phosphorylate myelin basic protein
GO:1904643 response to curcumin	IDA PMID:26449461 Curcumin inhibits development and cell adhesion in Dictyoste...	KEEP AS NON CORE	Summary: Curcumin suppresses members of the yakA-mediated developmental signaling pathway together with the prestarvation marker discoidin I and cell adhesion proteins, delaying development. Reason: The association is that curcumin acts on yakA-mediated signaling; this is a pharmacological/response annotation peripheral to the kinase's core function. Supporting Evidence: PMID:26449461 suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA)
GO:0006972 hyperosmotic response	IEP PMID:21288957 Bio-electrospraying and aerodynamically assisted bio-jetting...	KEEP AS NON CORE	Summary: yakA transcript is significantly induced under hyperosmotic (sorbitol) shock, identifying it as a hyperosmotic-stress-responsive gene. Reason: This IEP annotation reflects transcriptional induction of yakA by hyperosmotic stress rather than a demonstrated causal function; it is a non-core, expression-based association. Supporting Evidence: PMID:21288957 Our data confirm gapA, rtoA and yakA are commonly induced under hyperosmotic shock
GO:0006979 response to oxidative stress	IMP PMID:20670432 KeaA, a Dictyostelium Kelch-domain protein that regulates th...	ACCEPT	Summary: The KeaA study reiterates that YakA regulates survival to oxidative stress; keaA was isolated as a suppressor of the oxidative/nitrosative-stress death of yakA-null cells. Reason: Independent genetic evidence confirms YakA's role in the oxidative-stress response, consistent with the primary Taminato et al. study. Supporting Evidence: PMID:20670432 During growth YakA regulates the cell cycle, and the survival to oxidative, nitrosoative and thermal stresses
GO:0051409 response to nitrosative stress	IMP PMID:20670432 KeaA, a Dictyostelium Kelch-domain protein that regulates th...	ACCEPT	Summary: yakA-null cells are hypersensitive to nitrosative stress; suppressors of their nitrosative-stress-induced death (keaA) were used to dissect the YakA pathway, confirming YakA's role in the nitrosative-stress response. Reason: Genetic suppressor analysis in this study reinforces that YakA is required for survival under nitrosative stress. Supporting Evidence: PMID:20670432 During growth YakA regulates the cell cycle, and the survival to oxidative, nitrosoative and thermal stresses
GO:0030587 sorocarp development	HMP PMID:17659086 High-throughput analysis of spatio-temporal dynamics in Dict...	ACCEPT	Summary: In a high-throughput developmental phenotyping screen, yakA-disrupted cells fall into the 'developmentally null' cluster, failing to complete multicellular development into fruiting bodies. Reason: YakA is essential for the developmental program leading to sorocarp (fruiting body) formation; the high-throughput mutant phenotype places it among developmentally null genes. Supporting Evidence: PMID:17659086 This cluster includes a group of 'developmentally null' mutants in which genes such as mkpA, piaA, yakA and dagA are disrupted
GO:0007165 signal transduction	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	KEEP AS NON CORE	Summary: YakA participates in the chemoattractant/developmental signaling network, but signal transduction is a very general term. Reason: While YakA is a signaling kinase, this high-level term adds little specificity beyond the more informative developmental and stress-signaling annotations. Retained as non-core. Supporting Evidence: PMID:11410593 they play a role in G-protein-mediated signaling responses
GO:0005829 cytosol	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: Cytosolic localization is consistent with the direct YakA-GFP localization data. Reason: The cytosol localization is well supported by direct experimental evidence (YakA-GFP), so this traceable-author-statement annotation is correct. Supporting Evidence: PMID:11410593 We localized YakA-GFP to the cytosol
GO:0006935 chemotaxis	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	KEEP AS NON CORE	Summary: yakA-null cells have defects in G-protein-mediated chemotactic responses (folic acid-induced actin polymerization and cGMP accumulation), supporting a role in chemotaxis. Reason: YakA influences chemotactic signaling responses, but this is a downstream developmental consequence rather than the kinase's core catalytic or regulatory function. Supporting Evidence: PMID:11410593 The yakA-null cells have strong defects in folic acid-induced responses, such as actin polymerization and cGMP accumulation
GO:0031152 aggregation involved in sorocarp development	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: YakA is required for cells to enter development and aggregate; yakA-null cells fail to enter development, and YakA induces the cAMP-signaling machinery needed for aggregation. Reason: Aggregation is a core developmental process controlled by YakA through its induction of the cAMP relay (PKA-C, ACA, cAR1); yakA-null cells are aggregation-deficient. Supporting Evidence: PMID:11410593 yakA-null cells fail to enter development and display slow growth on bacterial lawns

Gene Description

Existing Annotations Review

Core Functions

YakA is a cytoplasmic dual-specificity (DYRK/MNB-subfamily) protein kinase that phosphorylates protein substrates on serine/threonine residues, as shown by direct in vitro phosphorylation of myelin basic protein.

YakA functions as a general sensor of environmental stress, required for cell-cycle arrest and survival under oxidative, nitrosative and heat stress through a cAMP/PKA-dependent pathway.

References

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