FNIP1
entrez
96459
canonical
uniprot
Q8TF40
canonical
ensembl
ENSG00000217128
resolver
ensp
ENSP00000309266
resolver
ensp
ENSP00000310453
resolver
ensp
ENSP00000421985
resolver
ensp
ENSP00000425619
resolver
enst
ENST00000307954
resolver
genesymbol
FNIP1
resolver
genesymbol_syn
KIAA1961
resolver
hgnc
HGNC:29418
resolver
uniprot
D6RJH5
resolver
uniprot
J3KNG8
resolver
uniprot
Q86T47
resolver
uniprot
Q9BUT0
resolver
uniprot_entry
FNIP1_HUMAN
resolver
uniprot_entry
J3KNG8_HUMAN
resolver
uniprot_sec
D6RJH5
resolver
uniprot_sec
Q86T47
resolver
uniprot_sec
Q9BUT0
resolver
amino_acid_sequence
MAPTLFQKLFSKRTGLGAPGRDARDPDCGFSWPLPEFDPSQIRLIVYQDCERRGRNVLFDSSVKRRNEDISVSKLGSDAQVKVFGKCCQLKPGGDSSSSLDSSVTSSSDIKDQCLKYQGSRCSSDANMLGEMMFGSVAMSYKGSTLKIHQIRSPPQLMLSKVFTARTGSSICGSLNTLQDSLEFINQDNNTLKADNNTVINGLLGNIGLSQFCSPRRAFSEQGPLRLIRSASFFAVHSNPMDMPGRELNEDRDSGIARSASLSSLLITPFPSPNSSLTRSCASSYQRRWRRSQTTSLENGVFPRWSIEESFNLSDESCGPNPGIVRKKKIAIGVIFSLSKDEDENNKFNEFFFSHFPLFESHMNKLKSAIEQAMKMSRRSADASQRSLAYNRIVDALNEFRTTICNLYTMPRIGEPVWLTMMSGTPEKNHLCYRFMKEFTFLMENASKNQFLPALITAVLTNHLAWVPTVMPNGQPPIKIFLEKHSSQSVDMLAKTHPYNPLWAQLGDLYGAIGSPVRLARTVVVGKRQDMVQRLLYFLTYFIRCSELQETHLLENGEDEAIVMPGTVITTTLEKGEIEESEYVLVTMHRNKSSLLFKESEEIRTPNCNCKYCSHPLLGQNVENISQQEREDIQNSSKELLGISDECQMISPSDCQEENAVDVKQYRDKLRTCFDAKLETVVCTGSVPVDKCALSESGLESTEETWQSEKLLDSDSHTGKAMRSTGMVVEKKPPDKIVPASFSCEAAQTKVTFLIGDSMSPDSDTELRSQAVVDQITRHHTKPLKEERGAIDQHQETKQTTKDQSGESDTQNMVSEEPCELPCWNHSDPESMSLFDEYFNDDSIETRTIDDVPFKTSTDSKDHCCMLEFSKILCTKNNKQNNEFCKCIETVPQDSCKTCFPQQDQRDTLSILVPHGDKESSDKKIAVGTEWDIPRNESSDSALGDSESEDTGHDMTRQVSSYYGGEQEDWAEEDEIPFPGSKLIEVSAVQPNIANFGRSLLGGYCSSYVPDFVLQGIGSDERFRQCLMSDLSHAVQHPVLDEPIAEAVCIIADMDKWTVQVASSQRRVTDNKLGKEVLVSSLVSNLLHSTLQLYKHNLSPNFCVMHLEDRLQELYFKSKMLSEYLRGQMRVHVKELGVVLGIESSDLPLLAAVASTHSPYVAQILL
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 93 and hypertrophic cardiomyopathy (IMD93) [MIM:619705]: An autosomal recessive disorder characterized by onset of recurrent viral and bacterial infections, particularly with encapsulated bacteria, and hypertrophic cardiomyopathy in the first months or years of life. {ECO:0000269|PubMed:32181500, ECO:0000269|PubMed:32905580}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). 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 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). 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 (PubMed:34597140). 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 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). 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 (PubMed:32905580). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:32905580, ECO:0000269|PubMed:34597140, ECO:0000269|PubMed:37079666}.
uniprot
proteins
mass_dalton
130555
uniprot
proteins
mutagenesis
MUTAGEN 220; /note="S->A: In SA5 mutant; Abolishes phosphorylation by AMPK, leading to activation of the non-canonical mTORC1 signaling; when associated with 230-A--A-232, A-261 and A-593."; /evidence="ECO:0000269|PubMed:37079666"; MUTAGEN 230..232; /note="SAS->AAA: In SA5 mutant; Abolishes phosphorylation by AMPK, leading to activation of the non-canonical mTORC1 signaling; when associated with A-220, A-261 and A-593."; /evidence="ECO:0000269|PubMed:37079666"; MUTAGEN 261; /note="S->A: In SA5 mutant; Abolishes phosphorylation by AMPK, leading to activation of the non-canonical mTORC1 signaling; when associated with A-220, 230-A--A-232 and A-593."; /evidence="ECO:0000269|PubMed:37079666"; MUTAGEN 593; /note="S->A: In SA5 mutant; Abolishes phosphorylation by AMPK, leading to activation of the non-canonical mTORC1 signaling; when associated with A-220, 230-A--A-232 and A-261."; /evidence="ECO:0000269|PubMed:37079666"; MUTAGEN 938..948; /note="SSDSALGDSES->EDEALGDEEE: Mimics phosphorylation status; leading to inhibit ATPase activity of HSP90AA1/Hsp90."; /evidence="ECO:0000269|PubMed:30699359"; MUTAGEN 938; /note="S->A: Impaired phosphorylation by CK2 and interaction with HSP90AA1/Hsp90."; /evidence="ECO:0000269|PubMed:30699359"; MUTAGEN 982; /note="K->R: No effect on ubiquitination and protein stability."; /evidence="ECO:0000269|PubMed:30699359"; MUTAGEN 1117; /note="K->R: No effect on ubiquitination and protein stability."; /evidence="ECO:0000269|PubMed:30699359"; MUTAGEN 1119; /note="K->R: Impaired ubiquitination, leading to increased stability."; /evidence="ECO:0000269|PubMed:30699359"; MUTAGEN 1134; /note="K->R: No effect on ubiquitination and protein stability."; /evidence="ECO:0000269|PubMed:30699359
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by AMPK in response to energetic stress (PubMed:17028174, 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 (PubMed:30699359). Priming phosphorylation at Ser-938 is followed by relay phosphorylation at Ser-939, Ser-941, Ser-946 and Ser-948, promoting its gradual interaction with HSP90AA1/Hsp90 (PubMed:30699359). This leads to incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients (PubMed:30699359). Dephosphorylated by protein phosphatase 5 (PP5), promoting glycosylation by OGT (PubMed:30699359). {ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:37079666}.; PTM: GlcNAcylation at Ser-938 by OGT following dephosphorylation by protein phosphatase 5 (PP5) promotes ubiquitination and degradation by the proteasome. {ECO:0000269|PubMed:30699359}.; PTM: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at Lys-1119 following glycosylation by OGT, leading to its degradation by the proteasome (PubMed:30699359). 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 (By similarity). Ubiquitination leads to FNIP1 degradation, and activation of mitochondria to recalibrate reactive oxygen species (ROS) (By similarity). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000269|PubMed:30699359}.; PTM: Oxidation of the Cys degron in normal conditions promotes its stabilization by preventing recognition and ubiquitination by the CRL2(FEM1B) complex. {ECO:0000250|UniProtKB:Q68FD7}.
uniprot
proteins
protein_family
FNIP family
uniprot
proteins
pubmed
11853319
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17028174
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18403135
uniprot
proteins
pubmed
18663353
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24081491
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25126726
uniprot
proteins
pubmed
27353360
uniprot
proteins
pubmed
29848618
uniprot
proteins
pubmed
30699359
uniprot
proteins
pubmed
32181500
uniprot
proteins
pubmed
32905580
uniprot
proteins
pubmed
34597140
uniprot
proteins
pubmed
37079666
uniprot
proteins
sequence_length
1166
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:29848618}. Cytoplasm, cytosol {ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:29848618}. Note=Localizes to lysosome membrane in amino acid-depleted conditions and relocalizes to the cytosol upon refeeding (PubMed:29848618). Colocalizes with FLCN in the cytoplasm (PubMed:18663353). {ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:29848618}.
uniprot
proteins