drkA (rk1/vsk1) encodes a Dictyostelium receptor-like kinase of the DRK subfamily within the tyrosine kinase-like (TKL) group. The 642-residue protein has a signal peptide, a Dictyostelium-specific extracellular domain shared with rk2, a single transmembrane helix and a C-terminal cytoplasmic protein kinase domain, an architecture typical of single-pass receptor kinases; its ligand is unknown. drkA is expressed almost exclusively in prestalk A (pstA) cells during multicellular development. Recombinant DrkA autophosphorylates on tyrosine and threonine and phosphorylates the STAT family transcription factor STATa on its activating Tyr702 residue in an SH2-dependent manner; over-expression increases STATa tyrosine phosphorylation in cells. DrkA is therefore a candidate direct STATa kinase acting in cAMP-induced STATa activation in prestalk cells, which is important for morphogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of protein kinase activity for a TKL-group receptor-like kinase with a canonical ePK domain (ATP-binding loop, catalytic proton acceptor D497). Consistent with direct experimental evidence that recombinant DrkA autophosphorylates and phosphorylates STATa. Reason: General but correct; experimentally corroborated by in vitro kinase assays. The more specific tyrosine kinase term captures the demonstrated substrate specificity. Supporting Evidence: PMID:31002205 recombinant DrkA protein is auto-phosphorylated on tyrosine and threonine residues PMID:31002205 an in vitro kinase assay shows that DrkA can phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding) domain-dependent manner |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based assignment from the protein kinase domain (IPR000719/IPR008271/IPR001245). Correct and supported by experimental kinase assays. Reason: Domain-based mapping is sound; activity verified experimentally. Supporting Evidence: PMID:31002205 recombinant DrkA protein is auto-phosphorylated on tyrosine and threonine residues |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: EC 2.7.11.1 mapping from the UniProt name "Probable serine/threonine-protein kinase". DrkA belongs to the TKL group; recombinant DrkA autophosphorylates on threonine as well as tyrosine, so some Ser/Thr activity is plausible, but no exogenous Ser/Thr substrate has been reported and the only characterized substrate (STATa) is phosphorylated on tyrosine. Reason: Threonine autophosphorylation supports a degree of Ser/Thr kinase activity (dual-specificity-like TKL), but the demonstrated physiological activity is tyrosine phosphorylation of STATa; retain as non-core. Supporting Evidence: PMID:31002205 recombinant DrkA protein is auto-phosphorylated on tyrosine and threonine residues |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:31002205 Analysis of DrkA kinase's role in STATa activation. | ACCEPT | Summary: Recombinant DrkA autophosphorylates on tyrosine and phosphorylates STATa on Tyr702 in vitro, in an SH2-dependent manner. This is the defining, experimentally demonstrated activity of DrkA. Reason: Direct in vitro kinase assay evidence (curator annotation from full text; abstract supports it). Supporting Evidence: PMID:31002205 an in vitro kinase assay shows that DrkA can phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding) domain-dependent manner PMID:31002205 recombinant DrkA protein is auto-phosphorylated on tyrosine and threonine residues |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning assignment of protein tyrosine kinase activity; concordant with the experimental IDA from the same group of evidence. Reason: Agrees with direct experimental evidence (PMID:31002205). Supporting Evidence: PMID:31002205 an in vitro kinase assay shows that DrkA can phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding) domain-dependent manner |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding inferred from the kinase domain glycine-rich loop (380-388) and conserved Lys401. Correct as a cofactor-binding feature of an active kinase but not informative beyond the kinase activity itself. Reason: Correct but subsumed by the catalytic activity. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: Root cellular_component ND annotation, placed when no localization data existed. DrkA has a predicted signal peptide and single transmembrane helix and already carries a membrane annotation. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the cellular component is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: REMOVE. Re-checked 2026-10-31: the DrkA study cited in core_functions (PMID:31002205) assays kinase activity, not localization. The gene's own literature-search record finds no study of this gene product in this species that identifies a cellular location. Supporting Evidence: file:DICDI/drkA/drkA-notes.md localization (plasma membrane vs vesicle) not experimentally established |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Inherited from a PANTHER node that includes many soluble cytoplasmic TKL kinases (e.g. RAF/LIMK-like members). DrkA is predicted to be a single-pass type I transmembrane receptor-like kinase whose kinase domain faces the cytoplasm, so "is_active_in cytoplasm" mis-describes a membrane-anchored protein. No experimental localization exists. Reason: Topology (signal peptide 1-23, extracellular 24-322, TM 323-343, cytoplasmic kinase 344-642) indicates membrane-anchored activity; cytoplasm reflects soluble family members rather than this receptor-like subfamily. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001148170 · PTN001148170 UNRESOLVED Node spans many soluble cytoplasmic TKL kinases; DrkA is a predicted single-pass type I receptor-like kinase, so membrane rather than cytoplasm is the expected compartment. Supporting Evidence: PMID:16596165 The Dictyostelium TKL group contains nine kinases with classic receptor kinase domain architectures, consisting of a signal peptide and a single transmembrane domain (TMD) flanking an extracellular region, and a C-terminal intracellular portion containing an ePK domain |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Generic signal transduction inferred phylogenetically. DrkA has receptor-kinase architecture and phosphorylates the transcription factor STATa, so participation in signal transduction is correct; the specific pathway is captured by GO:0097696. Reason: Correct but very general; the more specific STAT pathway term is the informative process annotation. Supporting Evidence: PMID:31002205 Transient over-expression of DrkA increased STATa phosphorylation |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane location from UniProt subcellular location (single-pass type I membrane protein, by similarity/prediction). Sequence features support a signal peptide and one transmembrane helix. Reason: Consistent with predicted topology and receptor-kinase architecture; the specific membrane (plasma membrane vs vesicle) is not established. Supporting Evidence: PMID:16596165 The Dictyostelium TKL group contains nine kinases with classic receptor kinase domain architectures, consisting of a signal peptide and a single transmembrane domain (TMD) flanking an extracellular region, and a C-terminal intracellular portion containing an ePK domain |
| GO:0097677 STAT family protein binding | IPI PMID:31002205 Analysis of DrkA kinase's role in STATa activation. | KEEP AS NON CORE | Summary: DrkA phosphorylates STATa on Tyr702 in an SH2-domain-dependent manner, implying a physical kinase-substrate interaction with STATa (dictyBase O00910 = STATa/dstA). Reason: Experimentally supported interaction; it reflects recognition of the substrate rather than a separate binding function, so the kinase activity is the core MF. Supporting Evidence: PMID:31002205 an in vitro kinase assay shows that DrkA can phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding) domain-dependent manner |
| GO:0097696 cell surface receptor signaling pathway via STAT | IMP PMID:31002205 Analysis of DrkA kinase's role in STATa activation. | ACCEPT | Summary: DrkA is expressed in prestalk A cells where STATa is activated by extracellular cAMP; altered DrkA levels change STATa tyrosine phosphorylation and DrkA directly phosphorylates STATa Tyr702. DrkA thus performs the activating phosphorylation step in cAMP-induced STATa signaling. Reason: DrkA does the work of the step (Tyr702 phosphorylation of STATa), satisfying the participation criterion. Curator annotation from full text; the abstract is consistent. Supporting Evidence: PMID:31002205 Transient over-expression of DrkA increased STATa phosphorylation PMID:31002205 an in vitro kinase assay shows that DrkA can phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding) domain-dependent manner |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MARK AS OVER ANNOTATED | Summary: Rhea-based mapping (RHEA:17989, seryl phosphorylation) derived from the generic EC 2.7.11.1 assignment. Experimental data show tyrosine and threonine autophosphorylation and tyrosine phosphorylation of STATa; no serine phosphorylation has been reported. Reason: Serine kinase activity is an unverified consequence of a family-level EC label; not supported by DrkA-specific evidence. Supporting Evidence: PMID:31002205 recombinant DrkA protein is auto-phosphorylated on tyrosine and threonine residues |
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Download this section (compressed HTML)Q: What extracellular ligand, if any, is sensed by the Dictyostelium-specific extracellular domain of DrkA, and does it link DrkA activity to cAMP or another prestalk signal?
Q: Is DrkA localized to the plasma membrane or to intracellular vesicles (as the vsk1 name suggests), and where does it encounter STATa?
Q: Does DrkA phosphorylate any exogenous Ser/Thr substrates, or is it functionally a tyrosine-selective TKL kinase?
Experiment: Assess STATa Tyr702 phosphorylation and STATa target gene expression in drkA null and kinase-dead knock-in strains after cAMP stimulation, with and without rk2 deletion to test redundancy.
Experiment: Determine DrkA subcellular localization in pstA cells using an endogenously tagged allele and live imaging.
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