kin-1

Gene 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 Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	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.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	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.
GO:0005952 cAMP-dependent protein kinase complex	IBA GO_REF:0000033	ACCEPT	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.
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	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.
GO:0004691 cAMP-dependent protein kinase activity	IBA GO_REF:0000033	ACCEPT	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.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	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.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000002	MODIFY	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. Proposed replacements: cAMP-dependent protein kinase activity
GO:0004690 cyclic nucleotide-dependent protein kinase activity	IEA GO_REF:0000117	MODIFY	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. Proposed replacements: cAMP-dependent protein kinase activity
GO:0004691 cAMP-dependent protein kinase activity	IEA GO_REF:0000003	ACCEPT	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.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	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.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MARK AS OVER ANNOTATED	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.
GO:0106310 protein serine kinase activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	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.

Gene Description

Existing Annotations Review

Core Functions

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.

Binds ATP in the conserved kinase active site as the phosphate donor for the protein phosphotransfer reaction.

References

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