Protein: Folliculin-interacting protein 2 (O6-methylguanine-induced apoptosis 1 protein) (Q80TD3)
Organism: Mus musculus (Mouse)
Function: 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. 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 (By similarity). 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 (By similarity). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (By similarity). 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 (By similarity). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (By similarity). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (By similarity). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions.
Subcellular location: Lysosome membrane {ECO:0000250|UniProtKB:Q9P278}. Cytoplasm {ECO:0000269|PubMed:19137017}. Note=Colocalizes with FLCN in the cytoplasm. {ECO:0000250|UniProtKB:Q9P278}.
Interaction partners:
- Folliculin
- Ras-related GTP-binding protein C
- Folliculin-interacting protein 1
- Ras-related GTP-binding protein D
- Ras-related GTP-binding protein B
- Ras-related GTP-binding protein A
- Neutral amino acid transporter 9
- Ragulator complex protein LAMTOR5
- Ragulator complex protein LAMTOR4
- Ragulator complex protein LAMTOR3
Sequence:
MAPTLLQKLFNKRGGGAASAQARPPKEEPAFSWSCSEFGLSDIRLLVYQDCERRGRQVMFDSRAVQKMEEAAAQKAEDVPIKMSARCCQESSSSSGSSSSGSSSSHGFGGSLQHAKQQLPKYQYTRPASDVSMLGEMMFGSVAMSYKGSTLKIHYIRSPPQLMISKVFSATMGSFCGSTNNLQDSFEYINQDPQAGKLNTNQYNLGPFRTGSNLAHSTPVDMPSRGQNEDRDSGIARSASLSSLLITPFPSPSSSTSSSSSYQRRWLRSQTTSLENGIFPRRSTDETFSLAEETCSSNPAMVRRKKIAISIIFSLCEREAAQRDFQDFFFSHFPLFESHMNRLKGAIEKAMISCRKISESSLRVQFYVSRLMEALGEFRGTIWNLYSVPRIAEPVWLTMMSNTLEKNQLCQRFLKEFILLIEQVNKNQFFAALLTAVLTYHLAWVPTVMPVDHPPIKAFSEKRTSQSVNMLAKTHPYNPLWAQLGDLYGAIGSPVRLTRTVVIGKQKDLVQRILYVLTYFLRCSELQENQLSWSGNPSEDDQVINGSKIITALEKGEVEESEYVVVTVSSEPALVPPILPQGTAERRSPEPTVVAEISEGVNTSELGHKPEKNRCKRPEQNSEASSMGFQEAEPDSSWIPQGIFCEDKQNDQEATQDCSSSPPSCEVPRVRRRMDQQTLHSKLHGETLKKRAEQSAAWPCPDRHSQEDPPVEKVTFHIGSSISPESDFESRTKRMEERLKACGHFHGASASASSSMDTGLTQEQQGSGCSFKADFEKDITPQDHSSGGEGVSEDRGLRANMTHAVGQLSQVDGPLAHSLCAAESGRRLLEQTRDVQLKGYKGPSSEPVPNRCRQQGGLLIAADVPYGDASGKGNYRSEGDIPRNESLDSALGDSDDEACVLALLELGHSCDRTEESLEVELPLPRSQSTSKANVRNFGRSLLAGYCATYMPDLVLHGTSSDEKLKQCLAADLVHTVHHPVLDEPIAEAVCIIADTDKWTVQVATSQRKVTDTMKLGQDVLVSSQVSSLLQSILQLYKLHLPADFCIMHLEDRLQEMYLKSKMLSEYLRGHTRVHVKELSVVLGIESNDLPLLTAIASTHSPYVAQILL