Fnip1
entrez
216742
canonical
uniprot
Q68FD7
canonical
ensembl
ENSMUSG00000035992
resolver
ensp
ENSMUSP00000049026
resolver
ensp
ENSMUSP00000162914
resolver
ensp
ENSMUSP00000162915
resolver
enst
ENSMUST00000046835
resolver
genesymbol
Fnip1
resolver
genesymbol_syn
Kiaa1961
resolver
uniprot
Q80T72
resolver
uniprot
Q8BQM0
resolver
uniprot_entry
FNIP1_MOUSE
resolver
uniprot_sec
Q80T72
resolver
uniprot_sec
Q8BQM0
resolver
amino_acid_sequence
MAPTLFQKLFSKRSGLGAPGRDARDPDCAFSWPLPEFDPSQIRLIVYQDCERRGRNVLFDSSVKRKNEDTSVSKLCNDAQVKVFGKCCQLKPGGDSSSSLDSSITLSSDGKDQCPKYQGSRCSSDANMLGEMMFGSVAMSYKGSTLKIHQIRSPPQLMLSKVFTARTGSSICGSLNTLQDSLEFINQDSNTLKADSSTVSNGLLGNIGLSQFCSPRRAFSEQGPLRLIRSASFFAVHSNPMDMPGRELNEDRDSGIARSASLSSLFITPFPSPNSSLTRSCASSYQRRWRRSQTTSLENGVFPRWSVEESFNLSDESCGPNPGIVRKKKIAIGVIFSLSKDEDENNKFNEFFFSHFPLFESHMNKLKSAIEQAMKMSRRSADASQRSLAYNRILDALTEFRTTICNLYTMPRIGEPVWLTMMSGTPEKNQLCHRFMKEFTFLMENASKNQFLPALITAVLTNHLAWVPTVMPNGQPPIKIFLEKHSSQSVGMLAKTHPYNPLWAQLGDLYGAIGSPVRLARTVVVGKRQDLVQRLLYFLTYFIRCSELQETHLLENGEDEAIVMPGTVITTTLEKGEIEESEYVLITMHRNKSSLLFKESEETRTPNCNCKYCSHPVLGQNTENVSQPEREDTQDNSKELLGISDECQKISPPDCQEENAVDVQQYRDKLRTCLDTKLETVVCTGSAPADKCVLSETCLEPREESWQNKELLDSDNHTGTAMRPTGIVVEKKPPDKNVPSAFSCEVTQTKVTFLIGDSMSPDSDTELRSQAVVDQINRHHSEPLKEDRGVADKHQESKITKDQSEDSDTQNIVSGESCELPCWSHSDPESMSLFDEYFNDDSIETRTIDDVPVKTSTDSKEYCCMLEYPKRLYTKTNKQKSELCKCIETVHQDSCNACFPQQDQRNSLSILVPHGDKESSDKKNAVGTEWDIPRNESSDSALGDSESEDTGPDIRRQAGGYCGGDQEDWTEEDEIPFPGSKLIEVSAVQPNIANFGRSLLGGYCSSYVPDFVLQGIGNDERLRQCLVSDLSHAVQHPVLDEPIAEAVCIIADMDKWTVQVASSQRRVTDNKLGKEVLVSSLVSNLLHSTLQLYKHNLSPNFCVMHLEDRLQELYFKSKMLSEYLRGQMRVHVKELGVVLGIESSDLPLLAAVASTHSPYVAQILL
uniprot
proteins
function
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 (PubMed:23582324). 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 (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 (By similarity). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (By similarity). Interaction with GABARAP also inhibits the non-canonical mTORC1 signaling cascade: GABARAP sequesters FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). 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 (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). 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 (PubMed:32941802). Required for B-cell development (PubMed:22709692, PubMed:27303042). {ECO:0000250|UniProtKB:Q8TF40, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:22709692, ECO:0000269|PubMed:23582324, ECO:0000269|PubMed:27303042, ECO:0000269|PubMed:32941802}.
uniprot
proteins
mass_dalton
130126
uniprot
proteins
mutagenesis
MUTAGEN 600; /note="S->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 601; /note="E->R: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 602; /note="E->R: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 603; /note="T->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 604; /note="R->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 605; /note="T->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 606; /note="P->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 607; /note="N->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 608; /note="C->S: Abolished recognition by the CRL2(FEM1B) complex and subsequent ubiquitination. Reduced zinc-binding."; /evidence="ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363"; MUTAGEN 609; /note="N->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 610; /note="C->S: Abolished recognition by the CRL2(FEM1B) complex and subsequent ubiquitination. Reduced zinc-binding."; /evidence="ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363"; MUTAGEN 611; /note="K->A: Reduced but not abolished recognition by the CRL2(FEM1B) complex."; /evidence="ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363"; MUTAGEN 612; /note="Y->A: Reduced but not abolished recognition by the CRL2(FEM1B) complex."; /evidence="ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363"; MUTAGEN 613; /note="C->S: Abolished recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 614; /note="S->A: Does not affect recognition by the CRL2(FEM1B) complex and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:32941802"; MUTAGEN 615; /note="H->A: Abolished recognition by the CRL2(FEM1B) complex and subsequent ubiquitination. Reduced zinc-binding."; /evidence="ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by AMPK in response to energetic stress (PubMed:37079666). Phosphorylation by AMPK in response to mitochondrial damage promotes inactivation of the non-canonical mTORC1 signaling, nuclear translocation of TFEB and TFE3, inducing transcription of lysosomal or autophagy genes (PubMed:37079666). Sequential phosphorylation by CK2 promotes its gradual interaction with HSP90AA1/Hsp90 (By similarity). Priming phosphorylation at Ser-937 is followed by relay phosphorylation at Ser-938, Ser-940, Ser-945 and Ser-947, promoting its gradual interaction with HSP90AA1/Hsp90 (By similarity). This leads to incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients (By similarity). Dephosphorylated by protein phosphatase 5 (PP5), promoting glycosylation by OGT (By similarity). {ECO:0000250|UniProtKB:Q8TF40, ECO:0000269|PubMed:37079666}.; PTM: GlcNAcylation at Ser-937 by OGT following dephosphorylation by protein phosphatase 5 (PP5) promotes ubiquitination and degradation by the proteasome. {ECO:0000250|UniProtKB:Q8TF40}.; PTM: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at Lys-1118 following glycosylation by OGT, leading to its degradation by the proteasome (By similarity). Ubiquitinated by the CRL2(FEM1B) complex in response to reductive stress: reductive stress causes reduction of the conserved Cys degron in FNIP1, followed by zinc-binding, zinc acting as a molecular glue for recognition by the CRL2(FEM1B) complex (PubMed:32941802, PubMed:34562363). Ubiquitination leads to FNIP1 degradation, and activation of mitochondria to recalibrate reactive oxygen species (ROS) (PubMed:32941802, PubMed:34562363). {ECO:0000250|UniProtKB:Q8TF40, ECO:0000269|PubMed:32941802, ECO:0000269|PubMed:34562363}.; PTM: Oxidation of the Cys degron in normal conditions promotes its stabilization by preventing recognition and ubiquitination by the CRL2(FEM1B) complex. {ECO:0000269|PubMed:32941802}.
uniprot
proteins
protein_family
FNIP family
uniprot
proteins
pubmed
12693553
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22709692
uniprot
proteins
pubmed
23582324
uniprot
proteins
pubmed
25775561
uniprot
proteins
pubmed
27303042
uniprot
proteins
pubmed
29897930
uniprot
proteins
pubmed
32941802
uniprot
proteins
pubmed
34562363
uniprot
proteins
pubmed
35412553
uniprot
proteins
pubmed
37079666
uniprot
proteins
sequence_length
1165
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8TF40}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q8TF40}. Note=Localizes to lysosome membrane in amino acid-depleted conditions and relocalizes to the cytosol upon refeeding. Colocalizes with FLCN in the cytoplasm. {ECO:0000250|UniProtKB:Q8TF40}.
uniprot
proteins