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FLCN a protein that is expressed in most tissues and that has no significant homology to other proteins. Involved in nutrient sensing through the AMPK and mTOR signaling pathways. Regulates lysosome function by promoting the mTORC1-dependent sequestration of transcription factor EB (TFEB). Required for the recruitment of mTORC1 to lysosomes by Rag GTPases. Amino acid depletion leads to its recruitment to the surface of lysosomes where it directly binds RagA, an interaction that is promoted by FNIP1. May be a tumor suppressor. Loss of function mutations cause Birt-Hogg-Dube syndrome (BHD), a disease characterized by fibrofolliculomas (hair follicle tumors), and predispositions for renal carcinoma, pneumothorax, and pulmonary cysts. These symptoms are similar to those that occur in TSC or tuberous sclerosis complex, suggesting the involvement in the same pathways as TSC1. Belongs to the folliculin family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Tumor suppressor
Chromosomal Location of Human Ortholog: 17p11.2
Cellular Component: cilium; cytoplasm; cytosol; lysosome; midbody; nucleus; plasma membrane
Molecular Function: protein binding; protein complex binding
Biological Process: hemopoiesis; in utero embryonic development; intercellular junction assembly; negative regulation of cell growth; negative regulation of cell migration; negative regulation of protein kinase B signaling cascade; negative regulation of Rho protein signal transduction; negative regulation of TOR signaling pathway; negative regulation of transcription from RNA polymerase II promoter; positive regulation of apoptosis; positive regulation of autophagy; positive regulation of cell adhesion; positive regulation of protein amino acid phosphorylation; positive regulation of TOR signaling pathway; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transforming growth factor beta receptor signaling pathway; regulation of cytokinesis; regulation of histone acetylation; regulation of protein amino acid phosphorylation; regulation of TOR signaling pathway; TOR signaling pathway
Disease: Birt-hogg-dube Syndrome; Colorectal Cancer; Pneumothorax, Primary Spontaneous; Renal Cell Carcinoma, Nonpapillary
Reference #:  Q8NFG4 (UniProtKB)
Alt. Names/Synonyms: BHD; BHD skin lesion fibrofolliculoma protein; Birt-Hogg-Dube syndrome protein; DKFZp547A118; FLCL; FLCN; FLJ45004; FLJ99377; Folliculin; MGC17998; MGC23445
Gene Symbols: FLCN
Molecular weight: 64,473 Da
Basal Isoelectric point: 5.83  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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