FNIP1_MOUSE
ID FNIP1_MOUSE Reviewed; 1165 AA.
AC Q68FD7; Q80T72; Q8BQM0;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Folliculin-interacting protein 1 {ECO:0000303|PubMed:25775561};
GN Name=Fnip1 {ECO:0000303|PubMed:25775561, ECO:0000312|MGI:MGI:2444668};
GN Synonyms=Kiaa1961 {ECO:0000303|PubMed:12693553};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpus striatum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 882-1165.
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-760; SER-763 AND SER-907, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593; SER-594; SER-760;
RP SER-763 AND SER-940, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Heart, Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22709692; DOI=10.1182/blood-2012-02-410407;
RA Baba M., Keller J.R., Sun H.W., Resch W., Kuchen S., Suh H.C., Hasumi H.,
RA Hasumi Y., Kieffer-Kwon K.R., Gonzalez C.G., Hughes R.M., Klein M.E.,
RA Oh H.F., Bible P., Southon E., Tessarollo L., Schmidt L.S., Linehan W.M.,
RA Casellas R.;
RT "The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dube syndrome is
RT required for murine B-cell development.";
RL Blood 120:1254-1261(2012).
RN [10]
RP FUNCTION.
RX PubMed=23582324; DOI=10.1016/j.cell.2013.03.012;
RA Betschinger J., Nichols J., Dietmann S., Corrin P.D., Paddison P.J.,
RA Smith A.;
RT "Exit from pluripotency is gated by intracellular redistribution of the
RT bHLH transcription factor Tfe3.";
RL Cell 153:335-347(2013).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=25775561; DOI=10.1073/pnas.1419502112;
RA Hasumi H., Baba M., Hasumi Y., Lang M., Huang Y., Oh H.F., Matsuo M.,
RA Merino M.J., Yao M., Ito Y., Furuya M., Iribe Y., Kodama T., Southon E.,
RA Tessarollo L., Nagashima K., Haines D.C., Linehan W.M., Schmidt L.S.;
RT "Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in
RT kidney tumor suppression in cooperation with Flcn.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1624-E1631(2015).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=27303042; DOI=10.1073/pnas.1607592113;
RA Siggs O.M., Stockenhuber A., Deobagkar-Lele M., Bull K.R., Crockford T.L.,
RA Kingston B.L., Crawford G., Anzilotti C., Steeples V., Ghaffari S.,
RA Czibik G., Bellahcene M., Watkins H., Ashrafian H., Davies B., Woods A.,
RA Carling D., Yavari A., Beutler B., Cornall R.J.;
RT "Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy,
RT and elevated AMPK activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E3706-E3715(2016).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=29897930; DOI=10.1371/journal.pone.0197973;
RA Centini R., Tsang M., Iwata T., Park H., Delrow J., Margineantu D.,
RA Iritani B.M., Gu H., Liggitt H.D., Kang J., Kang L., Hockenbery D.M.,
RA Raftery D., Iritani B.M.;
RT "Loss of Fnip1 alters kidney developmental transcriptional program and
RT synergizes with TSC1 loss to promote mTORC1 activation and renal cyst
RT formation.";
RL PLoS ONE 13:E0197973-E0197973(2018).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, OXIDATION, UBIQUITINATION, AND MUTAGENESIS
RP OF SER-600; GLU-601; GLU-602; THR-603; ARG-604; THR-605; PRO-606; ASN-607;
RP CYS-608; ASN-609; CYS-610; LYS-611; TYR-612; CYS-613; SER-614 AND HIS-615.
RX PubMed=32941802; DOI=10.1016/j.cell.2020.08.034;
RA Manford A.G., Rodriguez-Perez F., Shih K.Y., Shi Z., Berdan C.A., Choe M.,
RA Titov D.V., Nomura D.K., Rape M.;
RT "A cellular mechanism to detect and alleviate reductive stress.";
RL Cell 183:46-61(2020).
CC -!- FUNCTION: Binding partner of the GTPase-activating protein FLCN:
CC involved in the cellular response to amino acid availability by
CC regulating the mTORC1 signaling cascade controlling the MiT/TFE factors
CC TFEB and TFE3 (PubMed:23582324). In low-amino acid conditions,
CC component of the lysosomal folliculin complex (LFC) on the membrane of
CC lysosomes, which inhibits the GTPase-activating activity of FLCN,
CC thereby inactivating mTORC1 and promoting nuclear translocation of TFEB
CC and TFE3 (By similarity). Upon amino acid restimulation, disassembly of
CC the LFC complex liberates the GTPase-activating activity of FLCN,
CC leading to activation of mTORC1 and subsequent cytoplasmic retention of
CC TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to
CC lysosomes and interaction with Rag GTPases (By similarity). Together
CC with FLCN, regulates autophagy: following phosphorylation by ULK1,
CC interacts with GABARAP and promotes autophagy (By similarity). In
CC addition to its role in mTORC1 signaling, also acts as a co-chaperone
CC of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits
CC the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase
CC and non-kinase client proteins of HSP90AA1/Hsp90 (By similarity). Acts
CC as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (By
CC similarity). Competes with the activating co-chaperone AHSA1 for
CC binding to HSP90AA1, thereby providing a reciprocal regulatory
CC mechanism for chaperoning of client proteins (By similarity). Also acts
CC as a core component of the reductive stress response by inhibiting
CC activation of mitochondria in normal conditions: in response to
CC reductive stress, the conserved Cys degron is reduced, leading to
CC recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed
CC by proteasomal degradation and subsequent activation of mitochondria to
CC recalibrate reactive oxygen species (ROS) (PubMed:32941802). Required
CC for B-cell development (PubMed:22709692, PubMed:27303042).
CC {ECO:0000250|UniProtKB:Q8TF40, ECO:0000250|UniProtKB:Q9P278,
CC ECO:0000269|PubMed:22709692, ECO:0000269|PubMed:23582324,
CC ECO:0000269|PubMed:27303042, ECO:0000269|PubMed:32941802}.
CC -!- SUBUNIT: Homodimer and homomultimer. Heterodimer and heteromultimer
CC with FNIP2. Interacts with FLCN (via C-terminus) (By similarity).
CC Component of the lysosomal folliculin complex (LFC), composed of FLCN,
CC FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or
CC RRAGD/RagD GTP-bound, and Ragulator (By similarity). Interacts with
CC HSPCA and with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-
CC activated protein kinase (AMPK). Phosphorylated FLCN and AMPK are
CC preferentially bound. Interacts with HSP70, STIP1, PTGES3, CDC37, BRAF,
CC GCR and CDK4. Interacts with HSP90AA1; the interaction inhibits
CC HSP90AA1 ATPase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q8TF40, ECO:0000250|UniProtKB:Q9P278}.
CC -!- INTERACTION:
CC Q68FD7; Q8QZS3: Flcn; NbExp=3; IntAct=EBI-6911068, EBI-6911093;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8TF40}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q8TF40}. Note=Localizes to
CC lysosome membrane in amino acid-depleted conditions and relocalizes to
CC the cytosol upon refeeding. Colocalizes with FLCN in the cytoplasm.
CC {ECO:0000250|UniProtKB:Q8TF40}.
CC -!- PTM: Sequential phosphorylation by CK2 promotes its gradual interaction
CC with HSP90AA1/Hsp90. Priming phosphorylation at Ser-937 is followed by
CC relay phosphorylation at Ser-938, Ser-940, Ser-945 and Ser-947,
CC promoting its gradual interaction with HSP90AA1/Hsp90. This leads to
CC incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual
CC activation of both kinase and non-kinase clients. Dephosphorylated by
CC protein phosphatase 5 (PP5), promoting glycosylation by OGT.
CC Phosphorylated by AMPK. {ECO:0000250|UniProtKB:Q8TF40}.
CC -!- PTM: GlcNAcylation at Ser-937 by OGT following dephosphorylation by
CC protein phosphatase 5 (PP5) promotes ubiquitination and degradation by
CC the proteasome. {ECO:0000250|UniProtKB:Q8TF40}.
CC -!- PTM: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at
CC Lys-1118 following glycosylation by OGT, leading to its degradation by
CC the proteasome (By similarity). Ubiquitinated by the CRL2(FEM1B)
CC complex in response to reductive stress: reductive stress causes
CC reduction of the conserved Cys degron in FNIP1, leading to recognition
CC by the CRL2(FEM1B), subsequent FNIP1 degradation, and activation of
CC mitochondria to recalibrate reactive oxygen species (ROS)
CC (PubMed:32941802). {ECO:0000250|UniProtKB:Q8TF40,
CC ECO:0000269|PubMed:32941802}.
CC -!- PTM: Oxidation of the Cys degron in normal conditions promotes its
CC stabilization by preventing recognition and ubiquitination by the
CC CRL2(FEM1B) complex. {ECO:0000269|PubMed:32941802}.
CC -!- DISRUPTION PHENOTYPE: Mice develop normally but display defects in B-
CC cell development independent of mTOR activity (PubMed:22709692,
CC PubMed:27303042). B-cell development defects result from rapid caspase-
CC induced pre-B cell death (PubMed:22709692). Heterozygous mice show
CC caused a loss of marginal zone B-cells (PubMed:27303042). Mice also
CC develop cardiomyopathy characterized by left ventricular hypertrophy
CC and elevated AMPK activity (PubMed:25775561, PubMed:27303042). Mice do
CC not show strong susceptibility to kidney neoplasia (PubMed:22709692,
CC PubMed:25775561). They however display slightly enlarged kidney size
CC and slightly increased renal cyst formation, characterized by decreased
CC AMPK activation, increased mTOR activation and metabolic
CC hyperactivation (PubMed:29897930). Mice lacking both Fnip1 and Fnip2
CC show enlarged polycystic kidneys (PubMed:25775561).
CC {ECO:0000269|PubMed:22709692, ECO:0000269|PubMed:25775561,
CC ECO:0000269|PubMed:27303042, ECO:0000269|PubMed:29897930}.
CC -!- SIMILARITY: Belongs to the FNIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC33163.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC65856.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK122574; BAC65856.1; ALT_INIT; mRNA.
DR EMBL; AL596127; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC079892; AAH79892.1; -; mRNA.
DR EMBL; AK047814; BAC33163.1; ALT_INIT; mRNA.
DR CCDS; CCDS24698.1; -.
DR RefSeq; NP_776114.2; NM_173753.4.
DR PDB; 7ROY; X-ray; 2.90 A; G/H=590-619.
DR PDBsum; 7ROY; -.
DR AlphaFoldDB; Q68FD7; -.
DR SMR; Q68FD7; -.
DR BioGRID; 229777; 7.
DR IntAct; Q68FD7; 1.
DR STRING; 10090.ENSMUSP00000049026; -.
DR GlyGen; Q68FD7; 1 site.
DR iPTMnet; Q68FD7; -.
DR PhosphoSitePlus; Q68FD7; -.
DR EPD; Q68FD7; -.
DR jPOST; Q68FD7; -.
DR MaxQB; Q68FD7; -.
DR PaxDb; Q68FD7; -.
DR PeptideAtlas; Q68FD7; -.
DR PRIDE; Q68FD7; -.
DR ProteomicsDB; 271782; -.
DR Antibodypedia; 25902; 149 antibodies from 25 providers.
DR DNASU; 216742; -.
DR Ensembl; ENSMUST00000046835; ENSMUSP00000049026; ENSMUSG00000035992.
DR GeneID; 216742; -.
DR KEGG; mmu:216742; -.
DR UCSC; uc007ixx.2; mouse.
DR CTD; 96459; -.
DR MGI; MGI:2444668; Fnip1.
DR VEuPathDB; HostDB:ENSMUSG00000035992; -.
DR eggNOG; KOG3693; Eukaryota.
DR GeneTree; ENSGT00390000009391; -.
DR HOGENOM; CLU_003447_0_0_1; -.
DR InParanoid; Q68FD7; -.
DR OMA; FRECEWR; -.
DR OrthoDB; 303571at2759; -.
DR PhylomeDB; Q68FD7; -.
DR TreeFam; TF324090; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 216742; 6 hits in 72 CRISPR screens.
DR ChiTaRS; Fnip1; mouse.
DR PRO; PR:Q68FD7; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q68FD7; protein.
DR Bgee; ENSMUSG00000035992; Expressed in intercostal muscle and 224 other tissues.
DR ExpressionAtlas; Q68FD7; baseline and differential.
DR Genevisible; Q68FD7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0042030; F:ATPase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0001783; P:B cell apoptotic process; IMP:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IMP:MGI.
DR GO; GO:0002327; P:immature B cell differentiation; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0002904; P:positive regulation of B cell apoptotic process; IMP:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:2000973; P:regulation of pro-B cell differentiation; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:MGI.
DR InterPro; IPR037545; DENN_FNIP1/2.
DR InterPro; IPR028086; FNIP_C_dom.
DR InterPro; IPR026156; FNIP_fam.
DR InterPro; IPR028085; FNIP_mid_dom.
DR InterPro; IPR028084; FNIP_N_dom.
DR Pfam; PF14638; FNIP_C; 1.
DR Pfam; PF14637; FNIP_M; 1.
DR Pfam; PF14636; FNIP_N; 1.
DR PRINTS; PR02073; FOLLICULNIP1.
DR PROSITE; PS51836; DENN_FNIP12; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Glycoprotein; Isopeptide bond; Lysosome; Membrane;
KW Oxidation; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1165
FT /note="Folliculin-interacting protein 1"
FT /id="PRO_0000308485"
FT DOMAIN 37..478
FT /note="uDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 486..1091
FT /note="cDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 1101..1156
FT /note="dDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT REGION 92..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..811
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 912..970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 928..1165
FT /note="Interaction with HSP90AA1"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOTIF 608..615
FT /note="Cys degron"
FT /evidence="ECO:0000269|PubMed:32941802"
FT COMPBIAS 779..805
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 915..929
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 294
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 760
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 907
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 937
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 938
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 945
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT CARBOHYD 937
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT CROSSLNK 1118
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8TF40"
FT MUTAGEN 600
FT /note="S->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 601
FT /note="E->R: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 602
FT /note="E->R: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 603
FT /note="T->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 604
FT /note="R->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 605
FT /note="T->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 606
FT /note="P->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 607
FT /note="N->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 608
FT /note="C->S: Abolished recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 609
FT /note="N->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 610
FT /note="C->S: Abolished recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 611
FT /note="K->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 612
FT /note="Y->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 613
FT /note="C->S: Abolished recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 614
FT /note="S->A: Does not affect recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
FT MUTAGEN 615
FT /note="H->A: Abolished recognition by the CRL2(FEM1B)
FT complex and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:32941802"
SQ SEQUENCE 1165 AA; 130126 MW; A03A39AC2FB53D29 CRC64;
MAPTLFQKLF SKRSGLGAPG RDARDPDCAF SWPLPEFDPS QIRLIVYQDC ERRGRNVLFD
SSVKRKNEDT SVSKLCNDAQ VKVFGKCCQL KPGGDSSSSL DSSITLSSDG KDQCPKYQGS
RCSSDANMLG EMMFGSVAMS YKGSTLKIHQ IRSPPQLMLS KVFTARTGSS ICGSLNTLQD
SLEFINQDSN TLKADSSTVS NGLLGNIGLS QFCSPRRAFS EQGPLRLIRS ASFFAVHSNP
MDMPGRELNE DRDSGIARSA SLSSLFITPF PSPNSSLTRS CASSYQRRWR RSQTTSLENG
VFPRWSVEES FNLSDESCGP NPGIVRKKKI AIGVIFSLSK DEDENNKFNE FFFSHFPLFE
SHMNKLKSAI EQAMKMSRRS ADASQRSLAY NRILDALTEF RTTICNLYTM PRIGEPVWLT
MMSGTPEKNQ LCHRFMKEFT FLMENASKNQ FLPALITAVL TNHLAWVPTV MPNGQPPIKI
FLEKHSSQSV GMLAKTHPYN PLWAQLGDLY GAIGSPVRLA RTVVVGKRQD LVQRLLYFLT
YFIRCSELQE THLLENGEDE AIVMPGTVIT TTLEKGEIEE SEYVLITMHR NKSSLLFKES
EETRTPNCNC KYCSHPVLGQ NTENVSQPER EDTQDNSKEL LGISDECQKI SPPDCQEENA
VDVQQYRDKL RTCLDTKLET VVCTGSAPAD KCVLSETCLE PREESWQNKE LLDSDNHTGT
AMRPTGIVVE KKPPDKNVPS AFSCEVTQTK VTFLIGDSMS PDSDTELRSQ AVVDQINRHH
SEPLKEDRGV ADKHQESKIT KDQSEDSDTQ NIVSGESCEL PCWSHSDPES MSLFDEYFND
DSIETRTIDD VPVKTSTDSK EYCCMLEYPK RLYTKTNKQK SELCKCIETV HQDSCNACFP
QQDQRNSLSI LVPHGDKESS DKKNAVGTEW DIPRNESSDS ALGDSESEDT GPDIRRQAGG
YCGGDQEDWT EEDEIPFPGS KLIEVSAVQP NIANFGRSLL GGYCSSYVPD FVLQGIGNDE
RLRQCLVSDL SHAVQHPVLD EPIAEAVCII ADMDKWTVQV ASSQRRVTDN KLGKEVLVSS
LVSNLLHSTL QLYKHNLSPN FCVMHLEDRL QELYFKSKML SEYLRGQMRV HVKELGVVLG
IESSDLPLLA AVASTHSPYV AQILL
