ArticleProceedings of the National Academy of Sciences of the United States of America2017
Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Application of acute myocardial infarction-related key genes in noninvasive diagnosis: a comprehensive analysis based on transcriptome and single-cell transcriptome.Frontiers in genetics · 2026Article
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Comprehensive Analysis of the Putative Substratome of FAM20C, the Master Serine Kinase of the Secretory Pathway.Biomolecules · 2025Article
- FAM20C: A key protein kinase in multiple diseases.Genes & diseases · 2025Review
- Gingival proteomics reveals the role of TGF beta and YAP/TAZ signaling in Raine syndrome fibrosis.Scientific reports · 2024Article
- The Structural-Functional Crosstalk of the Calsequestrin System: Insights and Pathological Implications.Biomolecules · 2023Review
- Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis.Journal of translational medicine · 2023Article
- Passing the post: roles of posttranslational modifications in the form and function of extracellular matrix.American journal of physiology. Cell physiology · 2023Review
- Remodeling of the ryanodine receptor isoform 1 channel regulates the sweet and umami taste perception ofFundamental research · 2023Article
- Gene Polymorphism and Recurrent Atrial Fibrillation after Catheter Ablation: A Comprehensive Review.Reviews in cardiovascular medicine · 2023Review
- Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired CaInternational journal of molecular sciences · 2022Article
- Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.International journal of molecular sciences · 2021Review
- Mechanisms underlying pathological CaPflugers Archiv : European journal of physiology · 2021Review
- Fam20C in Human Diseases: Emerging Biological Functions and Therapeutic Implications.Frontiers in molecular biosciences · 2021Review
- Ras-transformation reduce FAM20C expression and osteopontin phosphorylation.Bioscience reports · 2020Article
- Two NovelGenes · 2020Article
- Ancestral roles of the Fam20C family of secreted protein kinases revealed inThe Journal of cell biology · 2019Article
- Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals.IUBMB life · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Precise Ca cycling through the sarcoplasmic reticulum (SR), a Ca storage organelle, is critical for proper cardiac muscle function. This cycling initially involves SR release of Ca via the ryanodine receptor, which is regulated by its interacting proteins junctin and triadin. The sarco/endoplasmic reticulum Ca ATPase (SERCA) pump then refills SR Ca stores. Histidine-rich Ca-binding protein (HRC) resides in the lumen of the SR, where it contributes to the regulation of Ca cycling by protecting stressed or failing hearts. The common Ser96Ala human genetic variant of HRC strongly correlates with life-threatening ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. However, the underlying molecular pathways of this disease remain undefined. Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts. Furthermore, a Ser96Asp HRC variant, which mimics constitutive phosphorylation of Ser96, diminished delayed aftercontractions in HRC null cardiac myocytes. This HRC phosphomimetic variant was also able to rescue the aftercontractions elicited by the Ser96Ala variant, demonstrating that phosphorylation of Ser96 is critical for the cardioprotective function of HRC. Phosphorylation of HRC on Ser96 regulated the interactions of HRC with both triadin and SERCA2a, suggesting a unique mechanism for regulation of SR Ca homeostasis. This demonstration of the role of Fam20C-dependent phosphorylation in heart disease will open new avenues for potential therapeutic approaches against arrhythmias.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.