Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.1 (Mg2+-ATPase)
 1,484 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Very recently, Haeuptle and colleagues described a new glycosylation defect due to RFT1 deficiency (CDG In). Accumulation of intracellular DolPP-GlcNAc(2)Man(5) with absence of cytosolic GlcNAc(2)Man(5) resembled the profile of a yeast mutant deficient in RFT1, a protein that is thought to have a role as a flippase. This is the first detailed description of the clinical phenotype of this patient. It was a severe disorder affecting intrauterine development and movement, and leading to intrauterine growth retardation. The child was born with several musculoskeletal abnormalities including arthrogryposis. Postnatally, severe reflux and irregular bowl movements contributed to failure to thrive. The patient showed very little development and no vision and suffered from drug-resistant epilepsy. Abnormal coagulation resulted in thrombosis and the patient died at the age of 4 years from a pulmonary embolus.
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PMID:Comprehensive description of the phenotype of the first case of congenital disorder of glycosylation due to RFT1 deficiency (CDG In). 1926 16

Progressive familial intrahepatic cholestasis type 1 (PFIC1) is caused by mutations in the gene encoding the phospholipid flippase ATP8B1. Apart from severe cholestatic liver disease, many PFIC1 patients develop extrahepatic symptoms characteristic of cystic fibrosis (CF), such as pulmonary infection, sweat gland dysfunction and failure to thrive. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel essential for epithelial fluid transport. Previously it was shown that CFTR transcript levels were strongly reduced in livers of PFIC1 patients. Here we have investigated the hypothesis that ATP8B1 is important for proper CFTR expression and function. We analyzed CFTR expression in ATP8B1-depleted intestinal and pulmonary epithelial cell lines and assessed CFTR function by measuring short-circuit currents across transwell-grown ATP8B1-depleted intestinal T84 cells and by a genetically-encoded fluorescent chloride sensor. In addition, we studied CFTR surface expression upon induction of CFTR transcription. We show that CFTR protein levels are strongly reduced in the apical membrane of human ATP8B1-depleted intestinal and pulmonary epithelial cell lines, a phenotype that coincided with reduced CFTR activity. Apical membrane insertion upon induction of ectopically-expressed CFTR was strongly impaired in ATP8B1-depleted cells. We conclude that ATP8B1 is essential for correct apical localization of CFTR in human intestinal and pulmonary epithelial cells, and that impaired CFTR localization underlies some of the extrahepatic phenotypes observed in ATP8B1 deficiency.
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PMID:The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator. 2730 31