kin-1

id: A8XW88
gene_symbol: kin-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6238
  label: Caenorhabditis briggsae
description: >-
  kin-1 encodes the catalytic subunit of cAMP-dependent protein kinase (protein
  kinase A, PKA), an AGC-family serine/threonine protein kinase (EC 2.7.11.11)
  that is the principal effector of cAMP signaling. In the inactive holoenzyme
  the catalytic subunit is held in an autoinhibited heterotetramer with two
  regulatory subunits (encoded by kin-2). Binding of cAMP to the regulatory
  subunits releases the active catalytic subunits, which then phosphorylate
  serine and threonine residues of substrate proteins, transducing extracellular
  signals received through G protein-coupled receptors and adenylate cyclase into
  changes in target-protein activity. The protein has the canonical bilobal
  protein-kinase fold with an ATP-binding pocket and a conserved catalytic Asp
  acting as the proton acceptor. Cbr-KIN-1 is the sole PKA catalytic subunit gene
  in Caenorhabditis and, like its C. elegans ortholog, is essential for larval
  development and contributes to diverse cAMP-regulated processes including
  neuromuscular signaling (e.g. rhythmic enteric muscle contraction), the control
  of oocyte meiotic maturation, and metabolic regulation. The gene produces
  multiple isoforms through alternative splicing.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      PKA catalytic subunits translocate to and act in the nucleus, where they
      phosphorylate transcriptional regulators (e.g. CREB family). This IBA
      annotation is consistent with the conserved function across the PKA-C
      orthology group. It is a genuine but non-core, condition-dependent
      localization for this gene; the principal active pool is cytosolic.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      The released active catalytic subunit acts in the cytosol, where it
      phosphorylates many cytoplasmic substrates. This localization is well
      supported across the orthology group and is the primary cellular
      compartment of action for PKA catalytic activity.
    action: ACCEPT
- term:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      The catalytic subunit forms a heterotetramer with two regulatory (kin-2)
      subunits, the inactive PKA holoenzyme. Membership in the cAMP-dependent
      protein kinase complex is a defining, well-supported feature of this
      protein and is appropriately captured.
    action: ACCEPT
- term:
    id: GO:0007189
    label: adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      As the terminal effector kinase of the cAMP cascade, PKA acts downstream
      of GPCR-stimulated adenylate cyclase and elevated cAMP. Involvement in this
      signaling pathway is consistent with the conserved role of the orthology
      group. Retained as a relevant but non-core process annotation; the core
      identity of the gene is its kinase activity.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      This is the core molecular function of the gene: the cAMP-dependent
      serine/threonine protein kinase activity of the PKA catalytic subunit.
      Strongly supported by orthology across the entire PKA-C family and by the
      UniProt functional annotation (EC 2.7.11.11). Accepted as a core function.
    action: ACCEPT
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Correct but more general than the specific cAMP-dependent protein kinase
      activity (GO:0004691) that this protein performs. A more precise term is
      available and already annotated, so this generic parent is over-general.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Accurate description of the enzyme's Ser/Thr kinase specificity, but a more
      informative and equally well-supported term (cAMP-dependent protein kinase
      activity, GO:0004691) better captures the actual function. Proposed to
      modify to the specific core term.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0004691
      label: cAMP-dependent protein kinase activity
- term:
    id: GO:0004690
    label: cyclic nucleotide-dependent protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Correct but one level too general: this protein is specifically a
      cAMP-dependent (not the broader cyclic nucleotide-dependent, which also
      encompasses cGMP-dependent) protein kinase. The more specific child term
      GO:0004691 is the appropriate function and is already annotated.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0004691
      label: cAMP-dependent protein kinase activity
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      EC 2.7.11.11 to GO mapping yielding the correct core molecular function.
      Consistent with the IBA-supported core annotation of the same term.
    action: ACCEPT
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      ATP binding is required for the phosphotransfer reaction; the protein has a
      canonical kinase ATP-binding pocket (glycine-rich loop and conserved Lys).
      A correct and core supporting molecular function for a protein kinase.
    action: ACCEPT
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      RHEA-based annotation reflecting the Ser-phosphorylation half-reaction. It
      is correct but more general than the cAMP-dependent protein kinase activity
      that defines this enzyme. Flagged as over-general relative to GO:0004691.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      Sequence-similarity transfer (from human PKA-C, UniProtKB:P21137) of the
      serine kinase reaction activity. Correct but more general than the specific
      cAMP-dependent protein kinase activity term; flagged as over-general
      relative to GO:0004691.
    action: MARK_AS_OVER_ANNOTATED
core_functions:
- description: >-
    Active catalytic subunit of cAMP-dependent protein kinase (PKA); upon
    cAMP-triggered release from the regulatory (kin-2) subunits it phosphorylates
    serine/threonine residues of substrate proteins, transducing cAMP signals.
  molecular_function:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
- description: >-
    Binds ATP in the conserved kinase active site as the phosphate donor for the
    protein phosphotransfer reaction.
  molecular_function:
    id: GO:0005524
    label: ATP binding
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:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []