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	MARK AS OVER ANNOTATED	Summary: DYRK-family kinases are named for dual-specificity tyrosine phosphorylation, but the tyrosine-kinase activity is confined to cis-autophosphorylation of the activation loop during folding; the mature enzyme is a substrate-directed Ser/Thr kinase. Annotating substrate-directed protein tyrosine kinase activity therefore overstates the function. Reason: The tyrosine-phosphorylation capacity of DYRK/MNB kinases is an intramolecular autophosphorylation event, not a trans-acting tyrosine kinase activity toward other proteins. The dual-specificity is better captured by the parent term protein serine/threonine/tyrosine kinase activity; a bare protein tyrosine kinase annotation implies substrate tyrosine phosphorylation that has not been demonstrated for YakA. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000624409 · PANTHER node for DYRK/YAK dual-specificity kinases SUPPORTS SOURCE BUT NOT TARGET DYRK kinases show tyrosine activity only as cis-autophosphorylation during folding; the mature enzyme is a substrate-directed Ser/Thr kinase, so a bare protein-tyrosine-kinase term overstates the function SGD:S000003677 · budding-yeast Yak1 kinase SUPPORTS SOURCE BUT NOT TARGET Yak1/DYRK autophosphorylates on tyrosine intramolecularly but does not act as a trans tyrosine kinase; the tyrosine-kinase term over-propagates 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	KEEP AS NON CORE	Summary: General protein kinase activity from InterPro domain mapping. Correct but less informative than the specific Ser/Thr/Tyr dual-specificity activity. Reason: YakA is a bona fide protein kinase, so this parent term is correct, but more specific terms (protein serine/threonine kinase activity, protein serine/threonine/tyrosine kinase activity) better capture its function. 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	MARK AS OVER ANNOTATED	Summary: Rhea/EC-derived electronic annotation of tyrosine kinase activity. As with the IBA tyrosine-kinase annotation, this reflects the dual-specificity autophosphorylation reaction rather than a demonstrated trans tyrosine kinase activity on protein substrates. Reason: The tyrosine-kinase capacity of DYRK kinases is limited to cis activation-loop autophosphorylation; a standalone protein tyrosine kinase annotation over-interprets the reaction mapping. The dual-specificity is better represented by GO:0004712. 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

📄 View Raw YAML

id: Q54QV3
gene_symbol: yakA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: YakA is a large cytoplasmic dual-specificity protein kinase of the
  CMGC/MNB-DYRK subfamily (a homolog of yeast Yak1p and mammalian DYRK2/DYRK3)
  that acts as the master regulator of the growth-to-development transition in
  Dictyostelium discoideum. During vegetative growth it controls the cell cycle,
  setting the interval between cell divisions; its overexpression arrests growth
  while yakA-null cells have an accelerated cell cycle and are smaller than
  wild-type. Upon starvation YakA reprograms gene expression, repressing
  growth-phase genes (including the translational repressor pufA) and inducing
  the earliest developmental genes. By lowering PufA, which otherwise blocks
  translation of pkaC mRNA, YakA raises the level of the PKA catalytic subunit
  (PKA-C), which in turn drives expression of the aggregation-stage adenylyl
  cyclase (acaA/ACA) and the cAMP receptor (carA/cAR1), enabling cAMP relay,
  chemotactic aggregation and fruiting-body (sorocarp) formation. YakA also
  functions as a general sensor of environmental stress and is required for
  cell-cycle arrest and survival under oxidative, nitrosative and heat stress,
  acting through a cAMP/PKA-dependent pathway, and its transcript is induced by
  starvation and by osmotic, oxidative and other stresses. The protein has a
  central protein kinase domain flanked by extensive low-complexity and
  disordered regions and phosphorylates generic substrates such as myelin basic
  protein in vitro.
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
        myelin basic protein
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Cytoplasmic localization is supported by direct evidence; YakA-GFP was
      localized to the cytosol.
    action: ACCEPT
    reason: Direct localization of YakA-GFP to the cytosol confirms the phylogenetic
      inference of cytoplasmic activity.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: We localized YakA-GFP to the cytosol suggesting that YakA may
        be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: DYRK-family kinases are named for dual-specificity tyrosine
      phosphorylation, but the tyrosine-kinase activity is confined to
      cis-autophosphorylation of the activation loop during folding; the mature
      enzyme is a substrate-directed Ser/Thr kinase. Annotating substrate-directed
      protein tyrosine kinase activity therefore overstates the function.
    action: MARK_AS_OVER_ANNOTATED
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: PANTHER:PTN000624409
        source_label: "PANTHER node for DYRK/YAK dual-specificity kinases"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "DYRK kinases show tyrosine activity only as cis-autophosphorylation during folding; the mature enzyme is a substrate-directed Ser/Thr kinase, so a bare protein-tyrosine-kinase term overstates the function"
      - source_id: SGD:S000003677
        source_label: "budding-yeast Yak1 kinase"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Yak1/DYRK autophosphorylates on tyrosine intramolecularly but does not act as a trans tyrosine kinase; the tyrosine-kinase term over-propagates"
    reason: The tyrosine-phosphorylation capacity of DYRK/MNB kinases is an
      intramolecular autophosphorylation event, not a trans-acting tyrosine kinase
      activity toward other proteins. The dual-specificity is better captured by
      the parent term protein serine/threonine/tyrosine kinase activity; a bare
      protein tyrosine kinase annotation implies substrate tyrosine phosphorylation
      that has not been demonstrated for YakA.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: a subclass of dual-specificity Yak-related kinases (Dyrk)
        with unknown function
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: General protein kinase activity from InterPro domain mapping. Correct
      but less informative than the specific Ser/Thr/Tyr dual-specificity activity.
    action: KEEP_AS_NON_CORE
    reason: YakA is a bona fide protein kinase, so this parent term is correct, but
      more specific terms (protein serine/threonine kinase activity, protein
      serine/threonine/tyrosine kinase activity) better capture its function.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
        myelin basic protein
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: 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
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Rhea/EC-derived electronic annotation of tyrosine kinase activity. As
      with the IBA tyrosine-kinase annotation, this reflects the dual-specificity
      autophosphorylation reaction rather than a demonstrated trans tyrosine kinase
      activity on protein substrates.
    action: MARK_AS_OVER_ANNOTATED
    reason: The tyrosine-kinase capacity of DYRK kinases is limited to cis
      activation-loop autophosphorylation; a standalone protein tyrosine kinase
      annotation over-interprets the reaction mapping. The dual-specificity is
      better represented by GO:0004712.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: a subclass of dual-specificity Yak-related kinases (Dyrk)
        with unknown function
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
        myelin basic protein
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location mapping to cytoplasm, consistent with the
      direct YakA-GFP cytosolic localization.
    action: ACCEPT
    reason: Cytoplasmic/cytosolic localization is directly established for YakA, so
      this electronic annotation is correct.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: We localized YakA-GFP to the cytosol
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Rhea-derived serine kinase activity, a subtype of the Ser/Thr kinase
      activity that is consistent with DYRK-family substrate specificity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
        myelin basic protein
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11410593
  qualifier: is_active_in
  review:
    summary: Direct experimental localization of YakA-GFP to the cytosol establishes
      the cytoplasm as the site of YakA activity.
    action: ACCEPT
    reason: This IDA annotation is the primary evidence for YakA's cytoplasmic
      localization and represents its core cellular location.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: We localized YakA-GFP to the cytosol
- term:
    id: GO:0008277
    label: regulation of G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:11410593
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: 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
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:10375515
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10375515
      supporting_text: The YakA protein kinase governs this transition by regulating
        the cell cycle, repressing growth-phase genes and inducing developmental
        genes
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:24373846
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:24373846
      supporting_text: 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
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:9584128
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: 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
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:24373846
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:12134067
      supporting_text: 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
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IMP
  original_reference_id: PMID:20670432
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20670432
      supporting_text: 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
- term:
    id: GO:0010225
    label: response to UV-C
  evidence_type: IDA
  original_reference_id: PMID:25858552
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:25858552
      supporting_text: failed to affect expression of car1, aca, yakA, crucial for
        regulating cell cycle exit and growth to differentiation transition
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:12134067
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:12134067
      supporting_text: yakA null cells are hypersensitive to nitrosoative/oxidative
        stress and that a second-site mutation in pkaC suppresses this sensitivity
- term:
    id: GO:0051409
    label: response to nitrosative stress
  evidence_type: IMP
  original_reference_id: PMID:12134067
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    reason: Mutant phenotype evidence directly supports a required role for YakA in
      survival under nitrosative stress through the cAMP/PKA pathway.
    supported_by:
    - reference_id: PMID:12134067
      supporting_text: yakA null cells are hypersensitive to nitrosoative/oxidative
        stress and that a second-site mutation in pkaC suppresses this sensitivity
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9584128
  qualifier: enables
  review:
    summary: Direct in vitro assay shows purified YakA phosphorylates myelin basic
      protein, providing experimental evidence of protein kinase activity.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9584128
      supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
        myelin basic protein
- term:
    id: GO:1904643
    label: response to curcumin
  evidence_type: IDA
  original_reference_id: PMID:26449461
  qualifier: involved_in
  review:
    summary: Curcumin suppresses members of the yakA-mediated developmental
      signaling pathway together with the prestarvation marker discoidin I and cell
      adhesion proteins, delaying development.
    action: KEEP_AS_NON_CORE
    reason: The association is that curcumin acts on yakA-mediated signaling; this
      is a pharmacological/response annotation peripheral to the kinase's core
      function.
    supported_by:
    - reference_id: PMID:26449461
      supporting_text: 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)
- term:
    id: GO:0006972
    label: hyperosmotic response
  evidence_type: IEP
  original_reference_id: PMID:21288957
  qualifier: acts_upstream_of_or_within
  review:
    summary: yakA transcript is significantly induced under hyperosmotic (sorbitol)
      shock, identifying it as a hyperosmotic-stress-responsive gene.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21288957
      supporting_text: Our data confirm gapA, rtoA and yakA are commonly induced
        under hyperosmotic shock
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:20670432
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    reason: Independent genetic evidence confirms YakA's role in the oxidative-stress
      response, consistent with the primary Taminato et al. study.
    supported_by:
    - reference_id: PMID:20670432
      supporting_text: During growth YakA regulates the cell cycle, and the survival
        to oxidative, nitrosoative and thermal stresses
- term:
    id: GO:0051409
    label: response to nitrosative stress
  evidence_type: IMP
  original_reference_id: PMID:20670432
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    reason: Genetic suppressor analysis in this study reinforces that YakA is
      required for survival under nitrosative stress.
    supported_by:
    - reference_id: PMID:20670432
      supporting_text: During growth YakA regulates the cell cycle, and the survival
        to oxidative, nitrosoative and thermal stresses
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: HMP
  original_reference_id: PMID:17659086
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17659086
      supporting_text: This cluster includes a group of 'developmentally null'
        mutants in which genes such as mkpA, piaA, yakA and dagA are disrupted
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: acts_upstream_of_or_within
  review:
    summary: YakA participates in the chemoattractant/developmental signaling
      network, but signal transduction is a very general term.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: they play a role in G-protein-mediated signaling responses
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: located_in
  review:
    summary: Cytosolic localization is consistent with the direct YakA-GFP
      localization data.
    action: ACCEPT
    reason: The cytosol localization is well supported by direct experimental
      evidence (YakA-GFP), so this traceable-author-statement annotation is correct.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: We localized YakA-GFP to the cytosol
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: YakA influences chemotactic signaling responses, but this is a
      downstream developmental consequence rather than the kinase's core catalytic
      or regulatory function.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: The yakA-null cells have strong defects in folic acid-induced
        responses, such as actin polymerization and cGMP accumulation
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11410593
      supporting_text: yakA-null cells fail to enter development and display slow
        growth on bacterial lawns
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: PMID:10375515
  title: Starvation promotes Dictyostelium development by relieving PufA inhibition
    of PKA translation through the YakA kinase pathway.
  findings:
  - statement: YakA governs the growth-to-development transition by regulating the
      cell cycle, repressing growth-phase genes and inducing developmental genes.
    supporting_text: The YakA protein kinase governs this transition by regulating
      the cell cycle, repressing growth-phase genes and inducing developmental genes
  - statement: YakA initiates development by inhibiting PufA, which represses
      translation of pkaC (PKA-C) mRNA.
    supporting_text: YakA regulates the initiation of development by inhibiting the
      expression of PufA
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary Kuspa-lab study establishing the YakA-PufA-PKA-C axis;
      abstract verified against PubMed.
- id: PMID:11410593
  title: The protein kinase YakA regulates g-protein-linked signaling responses during
    growth and development of Dictyostelium.
  findings:
  - statement: yakA-null cells resemble G-protein beta-subunit nulls, fail to enter
      development, and have defects in folic acid-induced (G-protein-mediated)
      responses.
    supporting_text: 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
  - statement: YakA-GFP localizes to the cytosol and YakA is proposed to be a
      functional homolog of mammalian Dyrk2/Dyrk3 dual-specificity kinases.
    supporting_text: We localized YakA-GFP to the cytosol suggesting that YakA may
      be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Provides the direct cytosolic localization and dual-specificity
      DYRK homology; abstract verified against PubMed.
- id: PMID:12134067
  title: Role for YakA, cAMP, and protein kinase A in regulation of stress responses
    of Dictyostelium discoideum cells.
  findings:
  - statement: yakA-null cells are hypersensitive to nitrosative/oxidative stress,
      and a second-site pkaC mutation suppresses this sensitivity.
    supporting_text: yakA null cells are hypersensitive to nitrosoative/oxidative
      stress and that a second-site mutation in pkaC suppresses this sensitivity
  - statement: YakA is necessary for the starvation-induced decrease in vegetative
      gene expression, including the decrease in pufA mRNA.
    supporting_text: 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
  - statement: YakA is a general sensor of environmental conditions that effects
      changes through PKA.
    supporting_text: Our findings indicate that YakA is a general sensor of
      environmental conditions effecting changes through PKA
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full-text open-access primary study; establishes YakA/cAMP/PKA in
      oxidative, nitrosative and heat stress responses.
- id: PMID:15473840
  title: Chemoattractant signaling in dictyostelium discoideum.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review of Dictyostelium chemoattractant signaling used as a
      traceable source for signal-transduction, chemotaxis, aggregation and cytosol
      annotations; abstract-only in cache, so specific YakA claims are supported by
      primary papers.
- id: PMID:17659086
  title: High-throughput analysis of spatio-temporal dynamics in Dictyostelium.
  findings:
  - statement: yakA-disrupted cells cluster with 'developmentally null' mutants,
      failing to complete multicellular development.
    supporting_text: This cluster includes a group of 'developmentally null' mutants
      in which genes such as mkpA, piaA, yakA and dagA are disrupted
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput mutant phenotyping placing yakA among
      developmentally null genes; supports sorocarp development annotation.
- id: PMID:20670432
  title: KeaA, a Dictyostelium Kelch-domain protein that regulates the response to
    stress and development.
  findings:
  - statement: YakA is an effector of starvation gene-expression changes, up-
      regulating pkaC, the adenylyl cyclase acaA and the cAMP receptor carA.
    supporting_text: 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
  - statement: YakA regulates the cell cycle during growth and survival to oxidative,
      nitrosative and thermal stresses.
    supporting_text: During growth YakA regulates the cell cycle, and the survival to
      oxidative, nitrosoative and thermal stresses
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Study of the YakA-pathway suppressor keaA; corroborates YakA's
      roles in stress survival and cAMP-signaling gene induction.
- id: PMID:21288957
  title: 'Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic
    Dictyostelium discoideum: assessing stress and developmental competency post treatment.'
  findings:
  - statement: yakA transcript is significantly induced under hyperosmotic (sorbitol)
      shock.
    supporting_text: Our data confirm gapA, rtoA and yakA are commonly induced under
      hyperosmotic shock
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Uses yakA as a stress-response marker gene; supports the
      expression-based hyperosmotic-response annotation but not a core function.
- id: PMID:24373846
  title: Glutathione initiates the development of Dictyostelium discoideum through
    the regulation of YakA.
  findings:
  - statement: yakA initiates development and induces the expression of PKA-C, ACA
      and cAR1, and its expression is regulated by intracellular glutathione.
    supporting_text: 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
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Places YakA downstream of glutathione and upstream of PKA-C/ACA/cAR1
      induction; supports positive regulation of developmental gene expression.
- id: PMID:25858552
  title: Response of Dictyostelium discoideum to UV-C and involvement of poly (ADP-ribose)
    polymerase.
  findings:
  - statement: UV-C affects expression of developmentally important genes including
      yakA that regulate cell-cycle exit and the growth-to-differentiation
      transition.
    supporting_text: failed to affect expression of car1, aca, yakA, crucial for
      regulating cell cycle exit and growth to differentiation transition
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: yakA analysed as a UV-C-responsive developmental gene; supports the
      non-core response-to-UV-C annotation.
- id: PMID:26449461
  title: 'Curcumin inhibits development and cell adhesion in Dictyostelium discoideum:
    Implications for YakA signaling and GST enzyme function.'
  findings:
  - statement: Curcumin suppresses members of the yakA-mediated developmental
      signaling pathway and delays development.
    supporting_text: 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)
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Pharmacological study; supports the non-core response-to-curcumin
      annotation via effects on yakA signaling.
- id: PMID:9584128
  title: YakA, a protein kinase required for the transition from growth to development
    in Dictyostelium.
  findings:
  - statement: Purified recombinant YakA phosphorylates myelin basic protein in
      vitro, demonstrating protein kinase activity.
    supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
      myelin basic protein
  - statement: yakA-null cells are smaller with an accelerated cell cycle, and
      conditional YakA expression arrests the cell cycle and promotes developmental
      gene expression.
    supporting_text: 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
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Founding paper defining YakA as the growth-to-development kinase;
      provides the direct in vitro kinase-activity evidence.
core_functions:
- description: 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.
  molecular_function:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:9584128
    supporting_text: Purified YakA expressed in E. coli is able to phosphorylate
      myelin basic protein
  - reference_id: PMID:11410593
    supporting_text: We localized YakA-GFP to the cytosol suggesting that YakA may be
      a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3
- description: Through its kinase activity YakA acts as the master regulator of the
    growth-to-development transition, reprogramming gene expression upon starvation
    by repressing growth-phase genes (including pufA) and inducing developmental
    genes, thereby raising PKA-C and switching on the cAMP-signaling machinery.
  molecular_function:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  directly_involved_in:
  - id: GO:0010468
    label: regulation of gene expression
  - id: GO:0030587
    label: sorocarp development
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:10375515
    supporting_text: The YakA protein kinase governs this transition by regulating
      the cell cycle, repressing growth-phase genes and inducing developmental genes
  - reference_id: PMID:20670432
    supporting_text: 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
- description: 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.
  molecular_function:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  directly_involved_in:
  - id: GO:0006979
    label: response to oxidative stress
  - id: GO:0051409
    label: response to nitrosative stress
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:12134067
    supporting_text: yakA null cells are hypersensitive to nitrosoative/oxidative
      stress and that a second-site mutation in pkaC suppresses this sensitivity
  - reference_id: PMID:12134067
    supporting_text: Our findings indicate that YakA is a general sensor of
      environmental conditions effecting changes through PKA

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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