id: O00418
gene_symbol: EEF2K
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: EEF2K (eukaryotic elongation factor 2 kinase, also called calcium/calmodulin-dependent
  eEF2 kinase) is an atypical protein kinase of the alpha-kinase family, structurally
  unrelated to the classical eukaryotic protein-kinase superfamily and instead related
  to the myosin heavy chain kinases. Its single physiological substrate is the translation
  elongation factor eEF2, which it phosphorylates on Thr56; this phosphorylation prevents
  eEF2 from binding the ribosome, inactivating it and slowing the rate of peptide-chain
  elongation, thereby down-regulating global protein synthesis. EEF2K activity is strictly
  calcium/calmodulin-dependent and is further tuned by phosphorylation from multiple
  upstream signaling kinases (AMPK and TRPM7 activate it; mTOR/S6K, RSK and others inhibit
  it), coupling translation elongation to nutrient, energy and stress status. It acts
  in the cytosol and, in neurons, contributes to activity-dependent regulation of dendritic/synaptic
  translation.
existing_annotations:
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic transfer placing EEF2K at the postsynaptic density, consistent
      with its documented role in regulating local translation in neurons.
    action: KEEP_AS_NON_CORE
    reason: A plausible neuronal site of action, but peripheral to EEF2K's core cytosolic
      eEF2-kinase function; retained as non-core.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0140245
    label: regulation of translation at postsynapse
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: EEF2K regulates activity-dependent local translation at the postsynapse
      via eEF2 phosphorylation; a recognized neuronal role.
    action: KEEP_AS_NON_CORE
    reason: A genuine specialized neuronal application of EEF2K's elongation-control
      function; non-core relative to its general molecular activity.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: The defining molecular function of EEF2K is phosphorylation of eEF2 to
      inhibit elongation. Supported by phylogenetic inference and abundant direct evidence.
    action: ACCEPT
    reason: This is the core, specific molecular function of EEF2K (EC 2.7.11.20).
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: phosphorylates the elongation factor EEF2 at a single site,
        renders it unable to bind ribosomes and thus inactive
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of generic Ser/Thr kinase activity. EEF2K does
      phosphorylate a threonine residue, but it is an alpha-kinase structurally unrelated
      to the conventional Ser/Thr protein-kinase superfamily; the specific eEF2-kinase
      term is more accurate.
    action: KEEP_AS_NON_CORE
    reason: Directionally correct (it is a Thr-directed kinase) but the generic term
      both under-specifies and slightly mischaracterizes the alpha-kinase; the core
      MF is elongation factor-2 kinase activity.
    supported_by:
    - reference_id: PMID:9144159
      supporting_text: do not contain any sequence motifs characteristic of the eukaryotic
        protein kinase superfamily
- term:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Automated assignment of the specific eEF2-kinase activity, redundant with
      and consistent with the experimental and IBA evidence.
    action: ACCEPT
    reason: Agrees with direct experimental evidence; core molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: phosphorylates the elongation factor EEF2 at a single site,
        renders it unable to bind ribosomes and thus inactive
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Automated assignment of calcium ion binding. EEF2K activity is calcium/calmodulin-dependent;
      calcium sensing is largely mediated through calmodulin binding rather than direct
      calcium binding by EEF2K.
    action: KEEP_AS_NON_CORE
    reason: Plausible in the context of calcium/calmodulin regulation, but the salient,
      experimentally supported interaction is with calmodulin; retained as non-core.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Automated assignment of calmodulin binding, consistent with the strict
      requirement of calmodulin for EEF2K activity.
    action: ACCEPT
    reason: Calmodulin binding is experimentally established and required for kinase
      activity; a core regulatory molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Interacts with Calmodulin/CALM1; this interaction is strictly
        required for phosphorylation activity
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding, the phosphate donor cofactor for the kinase reaction.
    action: ACCEPT
    reason: ATP is the cosubstrate of the eEF2 kinase reaction (eEF2 + ATP gives eEF2-phosphate
      + ADP); ATP binding is a supported and necessary molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Reaction=[translation elongation factor 2] + ATP = [translation
        elongation factor 2]-phosphate + ADP + H(+)
- term:
    id: GO:0002931
    label: response to ischemia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated phenotype/context association. EEF2K is activated under energy
      stress (via AMPK), so a role in ischemia is biologically plausible but indirect.
    action: KEEP_AS_NON_CORE
    reason: Context association consistent with EEF2K's energy-stress activation; non-core
      relative to its molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Upon activation by a variety of upstream kinases including AMPK
        or TRPM7
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Automated assignment of postsynaptic density localization, redundant with
      the IBA postsynaptic-density annotation.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal site of action; non-core relative to the cytosolic eEF2-kinase
      function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association. Insulin/mTOR signaling inhibits EEF2K (via
      S6K/RSK), linking it to insulin responses.
    action: KEEP_AS_NON_CORE
    reason: Consistent with EEF2K being a downstream target of insulin/mTOR signaling;
      non-core context annotation.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Phosphorylation by other kinases such as CDK1 and MAPK13 at
        Ser-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease EEF2K activity and
        promote protein synthesis
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association linking EEF2K activity to cell-survival/apoptosis
      outcomes, a downstream physiological consequence rather than a direct molecular
      action.
    action: KEEP_AS_NON_CORE
    reason: Downstream phenotypic association (EEF2K modulates survival under stress);
      non-core relative to its kinase function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: In turn, the rate of protein synthesis is reduced.
- term:
    id: GO:0043197
    label: dendritic spine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Automated assignment of dendritic spine localization, consistent with
      a neuronal role in local translation control.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal localization; non-core relative to the core cytosolic
      function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0045807
    label: positive regulation of endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association of EEF2K with endocytosis regulation; a
      downstream/indirect link not reflecting its direct molecular activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Indirect phenotypic association from automated transfer; not supported
      as a direct EEF2K function and uninformative for its core role.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0051965
    label: positive regulation of synapse assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated neuronal context association; a downstream developmental consequence
      of EEF2K-regulated translation rather than a direct function.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal/developmental association; non-core relative to the
      kinase function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0061003
    label: positive regulation of dendritic spine morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated neuronal context association linking EEF2K-controlled translation
      to dendritic spine morphogenesis.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal developmental association; non-core relative to the
      molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0071277
    label: cellular response to calcium ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association consistent with EEF2K being a calcium/calmodulin-activated
      kinase that transduces calcium signals into translational control.
    action: KEEP_AS_NON_CORE
    reason: Consistent with EEF2K's calcium/calmodulin dependence; non-core context
      annotation.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation
- term:
    id: GO:0071320
    label: cellular response to cAMP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association; cAMP/PKA signaling can modulate EEF2K activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible signaling-context association; non-core relative to the kinase
      function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Upon activation by a variety of upstream kinases including AMPK
        or TRPM7
- term:
    id: GO:0071454
    label: cellular response to anoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association. EEF2K is activated under energy/oxygen
      stress (AMPK), slowing elongation to conserve energy.
    action: KEEP_AS_NON_CORE
    reason: Consistent with EEF2K's energy-stress activation; non-core context annotation.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Upon activation by a variety of upstream kinases including AMPK
        or TRPM7
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Automated assignment placing EEF2K at the glutamatergic synapse, consistent
      with its neuronal role in NMDA/mGluR-driven local translation control.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal site of action; non-core relative to the cytosolic kinase
      function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0140245
    label: regulation of translation at postsynapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated assignment redundant with the IBA postsynaptic translation-regulation
      annotation.
    action: KEEP_AS_NON_CORE
    reason: Genuine neuronal application of EEF2K's elongation-control function; non-core.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:1990416
    label: cellular response to brain-derived neurotrophic factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated neuronal context association; BDNF signaling modulates eEF2
      phosphorylation via EEF2K.
    action: KEEP_AS_NON_CORE
    reason: Plausible neuronal signaling-context association; non-core relative to
      the kinase function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:1990637
    label: response to prolactin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Automated context association linking EEF2K to prolactin signaling; an
      indirect/peripheral link.
    action: MARK_AS_OVER_ANNOTATED
    reason: Indirect phenotypic association from automated transfer; not supported
      as a direct EEF2K function and uninformative for its core role.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Threonine kinase that regulates protein synthesis by controlling
        the rate of peptide chain elongation.
- term:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  evidence_type: EXP
  original_reference_id: PMID:11015200
  qualifier: enables
  review:
    summary: Experimental demonstration (domain mapping, kinetics) of EEF2K phosphorylating
      eEF2, with measured KM and Vmax.
    action: ACCEPT
    reason: Direct experimental support for the core eEF2-kinase activity.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: KM=1.2 uM for EEF2
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: IDA
  original_reference_id: PMID:23184662
  qualifier: involved_in
  review:
    summary: EEF2K undergoes calcium/calmodulin-dependent intramolecular autophosphorylation.
      Note that PMID:23184662 chiefly concerns CDK2 phosphorylation of the substrate
      eEF2 (Ser595), and discusses EEF2K's own regulatory phosphorylations only in
      passing; the strongest autophosphorylation evidence comes from dedicated studies
      such as PMID:9144159.
    action: KEEP_AS_NON_CORE
    reason: Autophosphorylation is a genuine EEF2K property (regulating its calcium/calmodulin
      dependence), but it is a regulatory feature rather than the core function, and
      the cited reference is not the primary autophosphorylation study.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-165758
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization, the principal compartment where
      EEF2K phosphorylates eEF2.
    action: ACCEPT
    reason: Cytosol is the core site of action for EEF2K's regulation of elongation.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: phosphorylates the elongation factor EEF2 at a single site,
        renders it unable to bind ribosomes and thus inactive
- term:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9144159
  qualifier: enables
  review:
    summary: Foundational direct evidence identifying and characterizing eEF-2 kinase
      activity as a new (alpha-kinase) class.
    action: ACCEPT
    reason: Direct experimental support for the core eEF2-kinase activity.
    supported_by:
    - reference_id: PMID:9144159
      supporting_text: eukaryotic elongation factor-2 kinase
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: IDA
  original_reference_id: PMID:9144159
  qualifier: enables
  review:
    summary: Direct evidence that EEF2K is a calmodulin-binding kinase (the original
      calcium/calmodulin-dependent eEF2 kinase characterization).
    action: ACCEPT
    reason: Calmodulin binding is directly demonstrated and required for activity;
      a core regulatory molecular function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Interacts with Calmodulin/CALM1; this interaction is strictly
        required for phosphorylation activity
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: IDA
  original_reference_id: PMID:9144159
  qualifier: involved_in
  review:
    summary: Direct evidence that EEF2K autophosphorylates, a regulatory property that
      modulates its calcium/calmodulin dependence.
    action: KEEP_AS_NON_CORE
    reason: Autophosphorylation is a genuine regulatory feature of EEF2K but secondary
      to its core eEF2-kinase function.
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: Autophosphorylated at multiple residues, Thr-348 being the major
        site.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: TAS
  original_reference_id: PMID:9144159
  qualifier: enables
  review:
    summary: General protein kinase activity, a parent of the specific eEF2-kinase
      activity.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the informative core MF is elongation factor-2 kinase
      activity.
    supported_by:
    - reference_id: PMID:9144159
      supporting_text: eukaryotic elongation factor-2 kinase
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:9144159
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, consistent with the cytosolic site where EEF2K
      acts on eEF2.
    action: ACCEPT
    reason: Correct compartment for EEF2K's core function (consistent with the Reactome
      cytosol annotation).
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: phosphorylates the elongation factor EEF2 at a single site,
        renders it unable to bind ribosomes and thus inactive
- term:
    id: GO:0006414
    label: translational elongation
  evidence_type: TAS
  original_reference_id: PMID:9144159
  qualifier: involved_in
  review:
    summary: EEF2K is involved in the regulation of translational elongation. By phosphorylating
      and inactivating eEF2 it negatively regulates elongation; the more precise process
      is negative regulation of translational elongation.
    action: MODIFY
    reason: EEF2K does not itself carry out elongation; it negatively regulates it.
      A regulation term better captures the function than the bare process term.
    proposed_replacement_terms:
    - id: GO:0045900
      label: negative regulation of translational elongation
    supported_by:
    - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
      supporting_text: renders it unable to bind ribosomes and thus inactive. In turn,
        the rate of protein synthesis is reduced.
- term:
    id: GO:0008135
    label: translation factor activity, RNA binding
  evidence_type: TAS
  original_reference_id: PMID:9144159
  qualifier: enables
  review:
    summary: This annotation mischaracterizes EEF2K as a translation factor. EEF2K
      is a kinase; its substrate eEF2 is the translation elongation factor. EEF2K does
      not have translation-factor or RNA-binding activity.
    action: REMOVE
    reason: Incorrect molecular function. EEF2K is an alpha-kinase that phosphorylates
      eEF2, not a translation factor or RNA-binding protein; the term likely arose
      from conflation with its substrate.
    supported_by:
    - reference_id: PMID:9144159
      supporting_text: eukaryotic elongation factor-2 kinase
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11015200
  title: Mapping the functional domains of elongation factor-2 kinase.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication (publications/PMID_11015200.md) PubMed title
      matches the YAML title exactly; cached abstract reports EEF2K is an alpha-kinase
      that phosphorylates eEF2 and that calmodulin binding is strictly required for
      activity, supporting the core Ca2+/calmodulin-dependent eEF2-kinase molecular
      function. Full text not cached but abstract anchors the claim."
  findings:
  - statement: EEF2K is an alpha-kinase that phosphorylates eEF2 (KM ~1.2 uM); calmodulin
      binding is strictly required for activity.
    reference_section_type: ABSTRACT
- id: PMID:23184662
  title: Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent
    kinase 2 regulates its inhibition by eEF2 kinase.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication (publications/PMID_23184662.md) PubMed title
      matches the YAML title exactly; abstract states eEF2K phosphorylates eEF2 on
      Thr56 to inactivate it, directly supporting the core eEF2-kinase molecular
      function (cited in core_functions)."
  findings:
  - statement: eEF2K phosphorylates eEF2 on Thr56, inactivating it; CDK2 phosphorylates
      eEF2 on Ser595, which regulates Thr56 phosphorylation by eEF2K during the cell
      cycle.
    reference_section_type: ABSTRACT
- id: PMID:9144159
  title: Identification of a new class of protein kinases represented by eukaryotic
    elongation factor-2 kinase.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication (publications/PMID_9144159.md) PubMed title
      matches the YAML title exactly; abstract establishes eEF2 kinase as the
      founding member of the alpha-kinase class, structurally distinct from
      conventional protein kinases, supporting the core protein-kinase molecular
      function and its mechanistic classification."
  findings:
  - statement: eEF-2 kinase defines a new class of protein kinases (alpha-kinases)
      structurally unrelated to the conventional eukaryotic protein-kinase superfamily,
      homologous to myosin heavy chain kinase A.
    reference_section_type: ABSTRACT
- id: Reactome:R-HSA-165758
  title: Reactome pathway involving EEF2K (cytosolic localization)
  findings: []
core_functions:
- description: Calcium/calmodulin-dependent alpha-kinase that phosphorylates the translation
    elongation factor eEF2 on Thr56, rendering eEF2 unable to bind the ribosome and
    thereby slowing peptide-chain elongation.
  molecular_function:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
    supporting_text: phosphorylates the elongation factor EEF2 at a single site, renders
      it unable to bind ribosomes and thus inactive
  - reference_id: PMID:23184662
    supporting_text: phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine
      56 (T56) by eEF2 kinase (eEF2K)
- description: By inactivating eEF2, EEF2K negatively regulates the rate of translational
    elongation, coupling protein synthesis to calcium, energy and stress signals (AMPK/TRPM7
    activation; mTOR/S6K/RSK inhibition).
  molecular_function:
    id: GO:0004686
    label: elongation factor-2 kinase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/EEF2K/EEF2K-uniprot.txt
    supporting_text: In turn, the rate of protein synthesis is reduced.
proposed_new_terms: []
suggested_questions:
- question: How is the balance of activating (AMPK, TRPM7) versus inhibitory (mTOR/S6K,
    RSK) phosphorylations on EEF2K integrated to set the elongation rate in different
    cellular states?
- question: Beyond eEF2, does EEF2K have any other physiological substrates, or is
    eEF2 truly its sole target?
suggested_experiments:
- description: Phosphoproteomics and in vitro kinase assays with purified EEF2K to
    test substrate specificity and confirm whether eEF2 is the only physiological substrate.
- description: Structure-function analysis of the alpha-kinase domain with calmodulin
    to define how calcium/calmodulin binding and autophosphorylation switch EEF2K between
    active and inactive states.