FNIP2

Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:18663353, PubMed:31672913, PubMed:36103527). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (By similarity). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (PubMed:31672913, PubMed:36103527). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:31672913). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:18403135). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:18403135). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:18403135). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity).

Phosphorylated by AMPK.

Belongs to the FNIP family.

Widely expressed with highest levels in muscle, nasal mucosa, salivary gland, uvula, fat, liver, heart, placenta and pancreas (PubMed:18403135, PubMed:18663353, PubMed:27353360). Moderately expressed in the lung, small intestine, kidney and brain. Lower levels detected in renal cell carcinoma than in normal kidney tissue (PubMed:18403135). Higher levels detected in oncocytoma tumors than in normal kidney. Higher levels detected in renal cell carcinoma tumors than in normal kidney tissue (PubMed:27353360).

• Lysosome membrane
• Cytoplasm
• Colocalizes with FLCN in the cytoplasm.

FNIPL, KIAA1450, MAPO1, FNIP2, Folliculin-interacting protein 2, FNIP1-like protein, O6-methylguanine-induced apoptosis 1 protein

• entrezGene:57600
• omim:612768
• swissprot:Q9P278

Proteins

Oncology

122115Da