ReviewThe Journal of biological chemistry
The ABCs of the atypical Fam20 secretory pathway kinases.
Review in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Phosphorylation beyond the plasma membrane: How secretory pathway kinases sculpt the cellular dialogue in cancer (Review).International journal of molecular medicine · 2026Review
- Enamel renal syndrome due to FAM20A mutations: challenging kidney management in view of nephrocalcinosis, hypophosphatemia and hypocalciuria.Orphanet journal of rare diseases · 2026Article
- Integrative analysis identifies PIGK as an oncogenic glycosylphosphatidylinositol transamidase subunit with prognostic, immunological, and therapeutic relevance in head and neck cancer.International journal of medical sciences · 2026Article
- Endogenous Phosphopeptidomics Analysis by Using Mesoporous IMAC Materials.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Heterologous Caseins: The Role of Phosphorylation in Their Functionality and How to Achieve It.Biomolecules · 2025Review
- Recent Advances in Enzymes and Chemoenzymatic Synthesis of Tetrasaccharide Linkage Region of Proteoglycans.Chembiochem : a European journal of chemical biology · 2025Review
- FAM20C: A key protein kinase in multiple diseases.Genes & diseases · 2025Review
- Orthodontic findings and treatment need in patients with amelogenesis imperfecta: a descriptive analysis.Head & face medicine · 2024Article
- In-Depth Endogenous Phosphopeptidomics of Serum with Zirconium(IV)-Grafted Mesoporous Silica Enrichment.Analytical chemistry · 2024Article
- Gingival proteomics reveals the role of TGF beta and YAP/TAZ signaling in Raine syndrome fibrosis.Scientific reports · 2024Article
- Article
- Alkali-treated titanium dioxide promotes formation of proteoglycan layer and altered calcification and immunotolerance capacity in bone marrow stem cell.Biochemistry and biophysics reports · 2023Article
- Ganoin and acrodin formation on scales and teeth in spotted gar: A vital role of enamelin in the unique process of enamel mineralization.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Article
- Deficiency ofInternational journal of molecular sciences · 2023Article
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- Passing the post: roles of posttranslational modifications in the form and function of extracellular matrix.American journal of physiology. Cell physiology · 2023Review
- Regulation of secretory pathway kinase or kinase-like proteins in human cancers.Frontiers in immunology · 2023Review
- Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.American journal of physiology. Cell physiology · 2023Article
- Synthesis ofAnnals of medicine · 2022Article
- Hypoplastic amelogenesis imperfecta, bilateral nephrolithiasis and FGF-23-mediated hypophosphataemia: a triad of FAM20A-related enamel renal syndrome.BMJ case reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The study of extracellular phosphorylation was initiated in late 19th century when the secreted milk protein, casein, and egg-yolk protein, phosvitin, were shown to be phosphorylated. However, it took more than a century to identify Fam20C, which phosphorylates both casein and phosvitin under physiological conditions. This kinase, along with its family members Fam20A and Fam20B, defined a new family with altered amino acid sequences highly atypical from the canonical 540 kinases comprising the kinome. Fam20B is a glycan kinase that phosphorylates xylose residues and triggers peptidoglycan biosynthesis, a role conserved from sponges to human. The protein kinase, Fam20C, conserved from nematodes to humans, phosphorylates well over 100 substrates in the secretory pathway with overall functions postulated to encompass endoplasmic reticulum homeostasis, nutrition, cardiac function, coagulation, and biomineralization. The preferred phosphorylation motif of Fam20C is SxE/pS, and structural studies revealed that related member Fam20A allosterically activates Fam20C by forming a heterodimeric/tetrameric complex. Fam20A, a pseudokinase, is observed only in vertebrates. Loss-of-function genetic alterations in the Fam20 family lead to human diseases such as amelogenesis imperfecta, nephrocalcinosis, lethal and nonlethal forms of Raine syndrome with major skeletal defects, and altered phosphate homeostasis. Together, these three members of the Fam20 family modulate a diverse network of secretory pathway components playing crucial roles in health and disease. The overarching theme of this review is to highlight the progress that has been made in the emerging field of extracellular phosphorylation and the key roles secretory pathway kinases play in an ever-expanding number of cellular processes.
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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.