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
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.
Identification and characterization of a novel folliculin-interacting protein FNIP2.
Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein.
Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization.
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FLCN inactivation was associated with nuclear localization and increased transcriptional activity of TFE3.
"FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization"
Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disordered RhoA signalling, epithelial polarization and cytokinesis.
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FLCN and p0071 partly colocalize at junctions and the cytokinetic midbody.
"Folliculin and p0071 partially co-localized at cell junctions and in mitotic cells, at the midbody during cytokinesis."
Birt-Hogg-Dube syndrome is a novel ciliopathy.
Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases.
The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1.
FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation.
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ULK1 overexpression was associated with FLCN phosphorylation, including the reported C-terminal sites.
"We reveal that the FLCN complex is regulated by ULK1 and elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN, which are induced by ULK1 overexpression."
Folliculin directs the formation of a Rab34-RILP complex to control the nutrient-dependent dynamic distribution of lysosomes.
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FLCN-DENN promotes active Rab34 loading onto RILP without detected Rab34 exchange activity in the tested assay.
"Using purified recombinant proteins, we show that the FLCN-DENN domain does not act as a GEF for Rab34, but rather, loads active Rab34 onto RILP"
Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα.
The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
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FLCN acts as an Hsp90 client, while its partners FNIP1 and FNIP2 act as cochaperones in the reported study.
"Here we show that the tumour suppressor FLCN is an Hsp90 client protein and its binding partners FNIP1/FNIP2 function as co-chaperones."
GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids.
Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex.
Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex.
A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome.
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Active RagC or RagD mutants restore TFEB phosphorylation in FLCN-deficient cells.
"Importantly, expression of active RagCS75L or RagDS77L mutants in FLCN KO cells rescued TFEB phosphorylation"
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TFEB depletion rescues mTORC1 hyperactivation in Flcn-knockout kidneys.
"TFEB is constitutively nuclear and active in Flcn-KO kidneys and its depletion rescues mTORC1 hyperactivation."
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The studied Flcn-knockout kidneys have increased RagC/RagD and other TFEB targets.
"Finally, the levels of RagC and RagD were increased, as well as the levels of other previously described TFEB targets"
The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect.
GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis.
Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation.
Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1.
A TBK1-independent primordial function of STING in lysosomal biogenesis.
Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2.
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A distinct mouse Bhd null allele was associated with early embryonic lethality and visceral-endoderm defects.
"BHD homozygous null (BHD(d/d)) mice displayed early embryonic lethality at E5.5-E6.5, showing defects in the visceral endoderm."
Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys.
Deficiency of FLCN in mouse kidney led to development of polycystic kidneys and renal neoplasia.
Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFβ-mediated transcription.
The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development.
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Conditional adult mouse Flcn deletion produces a pro-B block resembling the Fnip1-null phenotype.
"We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1(-/-) mice."
Regulation of mitochondrial oxidative metabolism by tumor suppressor FLCN.
The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue.
Tumor Suppressor Folliculin Regulates mTORC1 through Primary Cilia.
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The authors propose a ciliary FLCN–LKB1 recruitment model connected to AMPK activation.
"it is conceivable that FLCN recruits LKB1 through primary cilia before targeting it to basal bodies for AMPK activation."
FLCN source evidence, assay boundaries, phylogenetic replay and conservation policy