Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
A novel lipid-anchored A-kinase Anchoring Protein facilitates cAMP-responsive membrane events.
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AKAP18 targets PKA to the plasma membrane and couples it to the L-type calcium channel.
"targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel."
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Membrane anchoring is by N-terminal myristoylation and dual palmitoylation.
"Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively."
Alternative splicing regulates the subcellular localization of A-kinase anchoring protein 18 isoforms.
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All isoforms share one R-subunit binding site but differ in targeting.
"The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains."
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Alpha goes to lateral, beta to apical membranes in epithelial cells.
"When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane."
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Alpha and beta are membrane-targeted; gamma is cytosolic.
"The original AKAP18 (renamed AKAP18alpha) and AKAP18beta target the plasma membrane when expressed in HEK-293 cells, while AKAP18gamma is cytosolic."
AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex.
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Several unrelated AKAPs restore cAMP regulation of IKs interchangeably.
"coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes"
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The authors attribute the effect to PKA anchoring generally.
"We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs"
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The effect is modest relative to myocytes.
"However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes."
A novel leucine zipper targets AKAP15 and cyclic AMP-dependent protein kinase to the C terminus of the skeletal muscle Ca2+ channel and modulates its function.
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AKAP15 binds the CaV1.1 C-terminus through a leucine zipper.
"Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif."
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Disrupting it blocks voltage-dependent potentiation in skeletal muscle.
"Disruption of the LZ interaction effectively inhibits voltage-dependent potentiation of L-type Ca(2+) channels in skeletal muscle cells."
Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15.
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AKAP15 co-purifies with CaV1.2.
"A kinase-anchoring protein 15 (AKAP15) coimmunoprecipitates with CaV1.2 channels"
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It binds the CaV1.2 C-terminus via a leucine-zipper-like motif.
"Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif."
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Competing peptides inhibit beta-adrenergic regulation of CaV1.2 in myocytes.
"Disruption of PKA anchoring to CaV1.2 channels via AKAP15 using competing peptides markedly inhibits the beta-adrenergic regulation of CaV1.2 channels via the PKA pathway in ventricular myocytes."
Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.
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All AKAP7 isoforms were deleted.
"We generated an AKAP7 KO mouse in which all isoforms were deleted"
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Knockout cardiomyocytes respond normally to adrenergic stimulation.
"KO cardiomyocytes responded normally to adrenergic stimulation, as measured by whole-cell patch clamp or a fluorescent intracellular Ca(2+) indicator."
Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination.
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Deleting AKAP7 in dentate granule cells disrupts cAMP-initiated mossy fiber LTP.
"Genetic ablation of AKAP7 specifically from dentate granule cells results in disruption of MF-CA3 LTP directly initiated by cAMP"
AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.
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Crystal structure of the AKAP18beta PKA-binding domain bound to the RIIalpha D/D domain.
"Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA."
AKAP15 anchors cAMP-dependent protein kinase to brain sodium channels.
The A-kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+ channel.
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Co-expressed AKAP15 strongly reduces ENaC conductance in oocytes.
"oocytes coexpressing AKAP15 exhibited an 80% and 91% reduction in the amiloride-sensitive, whole-cell conductance in high and low Na+ conditions, respectively."
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The effect is PKA-independent.
"The reduced channel activity was unaffected by PKA activation or inhibition, indicating a PKA-independent mechanism."
UniProtKB O43687 (AKAP7_HUMAN) flat file
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The function line describes PKA targeting to the plasma membrane.
"FUNCTION: Targets the cAMP-dependent protein kinase (PKA) to the plasma"
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The gamma isoform is held in a separate entry, so this entry covers alpha and beta only.
"IsoId=Q9P0M2-1; Sequence=External;"
Affinage mechanistic annotation for AKAP7 (human)
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The affinage narrative attributes the 2H phosphoesterase activity to the long isoforms, which are not in this entry.
"Beyond scaffolding, the central 2H phosphoesterase domain of long isoforms binds AMP and functions as a 2',5'-phosphodiesterase"