FEATURES

FAMILY

DESCRIPTION

Also known as FNIP2_HUMAN, FNIP2, FNIPL, KIAA1450, MAPO1. Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:18663353, PubMed:31672913). 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). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention 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). Homodimer and homomultimer (PubMed:18403135, PubMed:27353360). Heterodimer and heteromultimer with FNIP1 (PubMed:18403135, PubMed:27353360). Interacts (via C-terminus) with FLCN (via C-terminus) (PubMed:18403135, PubMed:18663353, PubMed:27353360). Phosphorylated FLCN is preferentially bound (PubMed:18663353). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (PubMed:31704029, PubMed:31672913). Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (PubMed:18403135, PubMed:27353360). Interacts with HSP70, HSP90AA1, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4 (PubMed:27353360).

EXTERNAL LINKS

FNIP2

Folliculin-interacting protein 2

FNIP2

Molecular Synopsis