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
TreeGrafter-generated GO annotations
Combined Automated Annotation using Multiple IEA Methods
UniProt record for donkey FLCN (A0A8C4MM62)
UniProt Swiss-Prot record for human FLCN (Q8NFG4)
UniProt Swiss-Prot record for mouse Flcn (Q8QZS3)
FLCN: donkey-human sequence comparison
The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect.
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Human FLCN binds LDHA and acts as an uncompetitive inhibitor through an N-terminal flexible loop.
"we identify the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA"
The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1.
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FLCN-FNIP1/2 is a GAP for RagC/D but not RagA/B, and localizes to the lysosome on amino acid starvation.
"We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B."
Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex.
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Structure of FLCN-FNIP2 bound to the Rags and Ragulator identifies a conserved catalytic arginine finger on FLCN.
"Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger"
Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex.
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FLCN relocalizes from cytosol to lysosomes on starvation, where its RagC GAP activity is inhibited within the lysosomal folliculin complex.
"The RagC-GAP activity of FLCN was inhibited within the LFC, owing to displacement of a catalytically required arginine in FLCN from the RagC nucleotide."
A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome.
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FLCN-dependent RagC/D activation is required specifically for mTORC1 phosphorylation of TFEB, and constitutive TFEB drives the kidney phenotype of the mouse BHD model.
"We found that constitutive activation of TFEB is the main driver of the kidney abnormalities and mTORC1 hyperactivity in a mouse model of Birt-Hogg-Dubé syndrome."