FNIP1 — Folliculin interacting protein 1
FNIP1 belongs to a gene co-expression module in 5 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
FNIP1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD19⁺ B cells | B-cell activation B cell maturation | ADAM19, ARHGAP30, CD164, CD19, CD47, CLN8, CPEB4, ELK3 +15 more | View in SCUBA |
| Fibroblasts | Fibroblast Quiescence Housekeeping | BTG1, EIF1, EIF4A2, ID2, KLF2, KLF4, RHOB, SRSF5 +5 more | View in SCUBA |
| Gamma-delta T cells | DNA Damage Ubiquitin DNA/chromatin regulation | ACBD3, CDADC1, CTPS1, CWC25, ING3, KLHL18, RALGAPA1, RCOR1 +7 more | |
| Macrophages | Golgi-Endosome Trafficking Vesicular traficking | ACSL4, ADPGK, ARRDC3, ATXN7L3B, CLN8, DDB1, DNAJC2, ETS2 +26 more | View in SCUBA |
| Mucosal-associated invariant T cell | Epigenetic Chromatin Regulation DNA/chromatin regulation | ASXL1, CREBBP, GATAD2A, PELI1, PNRC1, RAPGEF1, RYBP, ZCCHC2 +1 more |
About the gene
| Synonyms | KIAA1961 |
|---|---|
| Chromosome | 5: 131641714-131797017 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Disease related genes, Predicted intracellular proteins |
Function
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. Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling. 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 inactivation of TFEB and TFE3. Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy. In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90. Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90. Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.