Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
A novel myocyte-specific gene Midori promotes the differentiation of P19CL6 cells into cardiomyocytes.
Cardiomyopathy in α-kinase 3 (ALPK3)-deficient mice.
Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy.
ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy.
Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere.
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Human cellular catalytic-cleft and overexpression experiments support a noncatalytic interpretation within the tested models; this does not negate the positive domain assay in another study.
"Our phosphoproteomic studies of ALPK3dIC/dIC hiPSC-CMs, which altered the conformation of the kinase domain, ALPK3sIC/sIC, which targeted the predicted aspartate residue critical for catalysis, and massive overexpression of ALPK3 in HEK293T cells indicated that none of these perturbations significantly affected phosphorylation across the proteome."
ALPK3 Functions as a Pseudokinase.
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The mouse catalytic domain showed no detectable activity in the reported assay with an active TRPM7 comparator.
"However, our experimental results revealed the absence of detectable kinase activity in ALPK3 under the tested conditions (Figure 1B)."
Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle.
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The positive targeted assay compares active and heat-denatured recombinant ALPK3 domain on a SQSTM1 immunoprecipitate; it is not a wholly purified two-protein system.
"One tube received 5 μg active ALPK3 kinase and one received 5 μg of heat-denatured ALPK3 kinase."
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Addition of recombinant ALPK3 domain increased phosphorylation at 500 sites in inhibitor-pretreated cardiomyocyte lysate; this is positive assay evidence within a complex lysate, not a direct ATP-binding measurement.
"Before the assay, lysates were treated with an irreversible pan-kinase inhibitor to block endogenous kinase activity32,33. When recombinant ALPK3 kinase was applied to lysates, we identified 500 phosphosites that were significantly elevated compared to controls."
α Protein Kinase 3 Is Essential for Neonatal and Adult Cardiac Function.
A Novel miniALPK3 Gene Therapy for ALPK3-Associated Cardiomyopathy.
Alpha protein kinase 3 gene therapy restores heart function in mouse and human models of cardiomyopathy.
UniProtKB reviewed entry ALPK3_HUMAN