FNIP1_HUMAN
ID FNIP1_HUMAN Reviewed; 1166 AA.
AC Q8TF40; D6RJH5; Q86T47; Q9BUT0;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Folliculin-interacting protein 1 {ECO:0000303|PubMed:17028174};
GN Name=FNIP1 {ECO:0000303|PubMed:17028174, ECO:0000312|HGNC:HGNC:29418};
GN Synonyms=KIAA1961 {ECO:0000303|PubMed:11853319};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH FLCN; HSPCA; PRKAA1;
RP PRKAB1 AND PRKAG1, PHOSPHORYLATION, TISSUE SPECIFICITY, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND VARIANTS CYS-76 AND ARG-648.
RX PubMed=17028174; DOI=10.1073/pnas.0603781103;
RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A.,
RA Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M.,
RA Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B.;
RT "Folliculin encoded by the BHD gene interacts with a binding protein,
RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT CYS-76.
RC TISSUE=Lung;
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 MRNA] OF 196-1166 (ISOFORM 3), AND VARIANT
RP ARG-648.
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 617-1166, AND VARIANT ARG-648.
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=18403135; DOI=10.1016/j.gene.2008.02.022;
RA Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A.,
RA Linehan W.M., Schmidt L.S.;
RT "Identification and characterization of a novel folliculin-interacting
RT protein FNIP2.";
RL Gene 415:60-67(2008).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18663353; DOI=10.1038/onc.2008.261;
RA Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., Zhang D.,
RA Abe M., Hagiwara Y., Takahashi K., Hino O.;
RT "Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel
RT Fnip1-like (FnipL/Fnip2) protein.";
RL Oncogene 27:5339-5347(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593; SER-594; SER-760 AND
RP SER-763, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-760 AND SER-763, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-760 AND SER-763, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24081491; DOI=10.1083/jcb.201307084;
RA Petit C.S., Roczniak-Ferguson A., Ferguson S.M.;
RT "Recruitment of folliculin to lysosomes supports the amino acid-dependent
RT activation of Rag GTPases.";
RL J. Cell Biol. 202:1107-1122(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220; THR-294 AND SER-296, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION.
RX PubMed=25126726; DOI=10.4161/auto.29640;
RA Dunlop E.A., Seifan S., Claessens T., Behrends C., Kamps M.A., Rozycka E.,
RA Kemp A.J., Nookala R.K., Blenis J., Coull B.J., Murray J.T.,
RA van Steensel M.A., Wilkinson S., Tee A.R.;
RT "FLCN, a novel autophagy component, interacts with GABARAP and is regulated
RT by ULK1 phosphorylation.";
RL Autophagy 10:1749-1760(2014).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP FUNCTION, SUBUNIT, INTERACTION WITH HSP70; HSP90AA1; FLCN; STIP1; PTGES3;
RP CDC37; BRAF; GCR AND CDK4, AND TISSUE SPECIFICITY.
RX PubMed=27353360; DOI=10.1038/ncomms12037;
RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D.,
RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W.,
RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W.,
RA Bratslavsky G., Mollapour M.;
RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance
RT drug binding.";
RL Nat. Commun. 7:12037-12037(2016).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=29848618; DOI=10.1083/jcb.201712177;
RA Meng J., Ferguson S.M.;
RT "GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag
RT GTPase heterodimer nucleotide status in response to amino acids.";
RL J. Cell Biol. 217:2765-2776(2018).
RN [17]
RP FUNCTION, INTERACTION WITH HSP90AA1, PHOSPHORYLATION AT SER-938; SER-939;
RP SER-941; SER-946 AND SER-948, GLYCOSYLATION AT SER-938, UBIQUITINATION AT
RP LYS-1119, AND MUTAGENESIS OF 938-SER--SER-948; SER-938; LYS-982; LYS-1117;
RP LYS-1119 AND LYS-1134.
RX PubMed=30699359; DOI=10.1016/j.celrep.2019.01.018;
RA Sager R.A., Woodford M.R., Backe S.J., Makedon A.M., Baker-Williams A.J.,
RA DiGregorio B.T., Loiselle D.R., Haystead T.A., Zachara N.E., Prodromou C.,
RA Bourboulia D., Schmidt L.S., Linehan W.M., Bratslavsky G., Mollapour M.;
RT "Post-translational regulation of FNIP1 creates a rheostat for the
RT molecular chaperone Hsp90.";
RL Cell Rep. 26:1344-1356(2019).
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:17028174, PubMed:18663353, PubMed:24081491). In
CC low-amino acid conditions, component of the lysosomal folliculin
CC complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-
CC activating activity of FLCN, thereby inactivating mTORC1 and promoting
CC nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid
CC restimulation, disassembly of the LFC complex liberates the GTPase-
CC activating activity of FLCN, leading to activation of mTORC1 and
CC subsequent cytoplasmic retention of TFEB and TFE3 (By similarity).
CC Required to promote FLCN recruitment to lysosomes and interaction with
CC Rag GTPases (PubMed:24081491). Together with FLCN, regulates autophagy:
CC following phosphorylation by ULK1, interacts with GABARAP and promotes
CC autophagy (PubMed:25126726). In addition to its role in mTORC1
CC signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following
CC gradual phosphorylation by CK2, inhibits the ATPase activity of
CC HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client
CC proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as
CC a scaffold to load client protein FLCN onto HSP90AA1/Hsp90
CC (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for
CC binding to HSP90AA1, thereby providing a reciprocal regulatory
CC mechanism for chaperoning of client proteins (PubMed:27353360). Also
CC acts 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 (By similarity). Required for B-cell development (By
CC similarity). {ECO:0000250|UniProtKB:Q68FD7,
CC ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174,
CC ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491,
CC ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360,
CC ECO:0000269|PubMed:30699359}.
CC -!- SUBUNIT: Homodimer and homomultimer (PubMed:18403135, PubMed:27353360).
CC Heterodimer and heteromultimer with FNIP2 (PubMed:18403135,
CC PubMed:27353360). Interacts with FLCN (via C-terminus)
CC (PubMed:17028174, PubMed:27353360). Component of the lysosomal
CC folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2),
CC RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound,
CC and Ragulator (By similarity). Interacts with HSPCA and with the
CC PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase
CC (AMPK) (PubMed:17028174). Phosphorylated FLCN and AMPK are
CC preferentially bound (PubMed:17028174). Interacts with HSP70, STIP1,
CC PTGES3, CDC37, BRAF, GCR and CDK4 (PubMed:27353360). Interacts with
CC HSP90AA1; the interaction inhibits HSP90AA1 ATPase activity
CC (PubMed:27353360, PubMed:30699359). {ECO:0000250|UniProtKB:Q9P278,
CC ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18403135,
CC ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359}.
CC -!- INTERACTION:
CC Q8TF40; Q8NFG4: FLCN; NbExp=5; IntAct=EBI-2946919, EBI-2970160;
CC Q8TF40; Q9P278: FNIP2; NbExp=7; IntAct=EBI-2946919, EBI-7597109;
CC Q8TF40; O95166: GABARAP; NbExp=5; IntAct=EBI-2946919, EBI-712001;
CC Q8TF40; Q9H0R8: GABARAPL1; NbExp=2; IntAct=EBI-2946919, EBI-746969;
CC Q8TF40; Q9Q2G4: ORF; Xeno; NbExp=3; IntAct=EBI-2946919, EBI-6248094;
CC Q8TF40-1; Q8NFG4-1: FLCN; NbExp=7; IntAct=EBI-15604805, EBI-15604776;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:29848618}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:18663353,
CC ECO:0000269|PubMed:29848618}. Note=Localizes to lysosome membrane in
CC amino acid-depleted conditions and relocalizes to the cytosol upon
CC refeeding (PubMed:29848618). Colocalizes with FLCN in the cytoplasm
CC (PubMed:18663353). {ECO:0000269|PubMed:18663353,
CC ECO:0000269|PubMed:29848618}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TF40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TF40-2; Sequence=VSP_028982, VSP_028983;
CC Name=3;
CC IsoId=Q8TF40-3; Sequence=VSP_028984;
CC -!- TISSUE SPECIFICITY: Strong expression is found in the heart, liver
CC placenta, muscle, nasal mucosa, salivary gland and uvula and moderate
CC expression in kidney and lung. Higher levels detected in clear cell
CC renal cell carcinoma (RCC) and chromophobe RCC than in normal kidney
CC tissue. {ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18403135,
CC ECO:0000269|PubMed:27353360}.
CC -!- PTM: Sequential phosphorylation by CK2 promotes its gradual interaction
CC with HSP90AA1/Hsp90 (PubMed:30699359). Priming phosphorylation at Ser-
CC 938 is followed by relay phosphorylation at Ser-939, Ser-941, Ser-946
CC and Ser-948, promoting its gradual interaction with HSP90AA1/Hsp90
CC (PubMed:30699359). This leads to incremental inhibition of
CC HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase
CC and non-kinase clients (PubMed:30699359). Dephosphorylated by protein
CC phosphatase 5 (PP5), promoting glycosylation by OGT (PubMed:30699359).
CC Phosphorylated by AMPK (PubMed:17028174). {ECO:0000269|PubMed:17028174,
CC ECO:0000269|PubMed:30699359}.
CC -!- PTM: GlcNAcylation at Ser-938 by OGT following dephosphorylation by
CC protein phosphatase 5 (PP5) promotes ubiquitination and degradation by
CC the proteasome. {ECO:0000269|PubMed:30699359}.
CC -!- PTM: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at
CC Lys-1119 following glycosylation by OGT, leading to its degradation by
CC the proteasome (PubMed:30699359). 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) (By
CC similarity). {ECO:0000250|UniProtKB:Q68FD7,
CC ECO:0000269|PubMed:30699359}.
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:0000250|UniProtKB:Q68FD7}.
CC -!- SIMILARITY: Belongs to the FNIP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FNIP1ID44003ch5q23.html";
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DR EMBL; DQ145719; AAZ65854.1; -; mRNA.
DR EMBL; AC004227; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001956; AAH01956.1; -; mRNA.
DR EMBL; AB075841; BAB85547.1; -; mRNA.
DR EMBL; AL832008; CAD91145.1; -; mRNA.
DR CCDS; CCDS34226.1; -. [Q8TF40-3]
DR CCDS; CCDS34227.1; -. [Q8TF40-1]
DR CCDS; CCDS87321.1; -. [Q8TF40-2]
DR RefSeq; NP_001008738.2; NM_001008738.2. [Q8TF40-3]
DR RefSeq; NP_001333042.1; NM_001346113.1. [Q8TF40-2]
DR RefSeq; NP_588613.2; NM_133372.2. [Q8TF40-1]
DR AlphaFoldDB; Q8TF40; -.
DR BioGRID; 125175; 34.
DR DIP; DIP-57169N; -.
DR IntAct; Q8TF40; 12.
DR MINT; Q8TF40; -.
DR STRING; 9606.ENSP00000421985; -.
DR GlyGen; Q8TF40; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TF40; -.
DR PhosphoSitePlus; Q8TF40; -.
DR BioMuta; FNIP1; -.
DR DMDM; 313104236; -.
DR EPD; Q8TF40; -.
DR jPOST; Q8TF40; -.
DR MassIVE; Q8TF40; -.
DR MaxQB; Q8TF40; -.
DR PaxDb; Q8TF40; -.
DR PeptideAtlas; Q8TF40; -.
DR PRIDE; Q8TF40; -.
DR ProteomicsDB; 74549; -. [Q8TF40-1]
DR ProteomicsDB; 74550; -. [Q8TF40-2]
DR ProteomicsDB; 74551; -. [Q8TF40-3]
DR Antibodypedia; 25902; 149 antibodies from 25 providers.
DR DNASU; 96459; -.
DR Ensembl; ENST00000307968.11; ENSP00000309266.7; ENSG00000217128.13. [Q8TF40-3]
DR Ensembl; ENST00000510461.6; ENSP00000421985.1; ENSG00000217128.13. [Q8TF40-1]
DR Ensembl; ENST00000511848.1; ENSP00000425619.1; ENSG00000217128.13. [Q8TF40-2]
DR GeneID; 96459; -.
DR KEGG; hsa:96459; -.
DR MANE-Select; ENST00000510461.6; ENSP00000421985.1; NM_133372.3; NP_588613.3.
DR UCSC; uc003kvs.2; human. [Q8TF40-1]
DR CTD; 96459; -.
DR DisGeNET; 96459; -.
DR GeneCards; FNIP1; -.
DR HGNC; HGNC:29418; FNIP1.
DR HPA; ENSG00000217128; Low tissue specificity.
DR MIM; 610594; gene.
DR neXtProt; NX_Q8TF40; -.
DR OpenTargets; ENSG00000217128; -.
DR PharmGKB; PA142671758; -.
DR VEuPathDB; HostDB:ENSG00000217128; -.
DR eggNOG; KOG3693; Eukaryota.
DR GeneTree; ENSGT00390000009391; -.
DR HOGENOM; CLU_026421_0_0_1; -.
DR InParanoid; Q8TF40; -.
DR OMA; FRECEWR; -.
DR OrthoDB; 303571at2759; -.
DR PhylomeDB; Q8TF40; -.
DR TreeFam; TF324090; -.
DR PathwayCommons; Q8TF40; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q8TF40; -.
DR SIGNOR; Q8TF40; -.
DR BioGRID-ORCS; 96459; 27 hits in 1084 CRISPR screens.
DR ChiTaRS; FNIP1; human.
DR GenomeRNAi; 96459; -.
DR Pharos; Q8TF40; Tbio.
DR PRO; PR:Q8TF40; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8TF40; protein.
DR Bgee; ENSG00000217128; Expressed in cardiac muscle of right atrium and 197 other tissues.
DR ExpressionAtlas; Q8TF40; baseline and differential.
DR Genevisible; Q8TF40; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0042030; F:ATPase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0002327; P:immature B cell differentiation; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0002904; P:positive regulation of B cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:2000973; P:regulation of pro-B cell differentiation; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:UniProtKB.
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 Alternative splicing; Cytoplasm; Glycoprotein; Isopeptide bond; Lysosome;
KW Membrane; Oxidation; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1166
FT /note="Folliculin-interacting protein 1"
FT /id="PRO_0000308484"
FT DOMAIN 37..478
FT /note="uDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 486..1092
FT /note="cDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 1102..1157
FT /note="dDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT REGION 781..817
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 912..956
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..1166
FT /note="Interaction with HSP90AA1"
FT /evidence="ECO:0000269|PubMed:27353360"
FT MOTIF 608..615
FT /note="Cys degron"
FT /evidence="ECO:0000250|UniProtKB:Q68FD7"
FT COMPBIAS 781..803
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 912..930
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 294
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 760
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 938
FT /note="Phosphoserine; alternate; by CK2"
FT /evidence="ECO:0000269|PubMed:30699359"
FT MOD_RES 939
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:30699359"
FT MOD_RES 941
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:30699359"
FT MOD_RES 946
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:30699359"
FT MOD_RES 948
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:30699359"
FT CARBOHYD 938
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:30699359"
FT CROSSLNK 1119
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:30699359"
FT VAR_SEQ 208..235
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_028984"
FT VAR_SEQ 508
FT /note="D -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028982"
FT VAR_SEQ 509..1166
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028983"
FT VARIANT 76
FT /note="G -> C (in dbSNP:rs7730228)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17028174"
FT /id="VAR_036824"
FT VARIANT 354
FT /note="S -> L (in dbSNP:rs13177318)"
FT /id="VAR_036825"
FT VARIANT 648
FT /note="Q -> R (in dbSNP:rs26008)"
FT /evidence="ECO:0000269|PubMed:11853319,
FT ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:17974005"
FT /id="VAR_036826"
FT VARIANT 738
FT /note="V -> L (in dbSNP:rs12109782)"
FT /id="VAR_036827"
FT VARIANT 844
FT /note="I -> V (in dbSNP:rs7717874)"
FT /id="VAR_036828"
FT MUTAGEN 938..948
FT /note="SSDSALGDSES->EDEALGDEEE: Mimics phosphorylation
FT status; leading to inhibit ATPase activity of
FT HSP90AA1/Hsp90."
FT /evidence="ECO:0000269|PubMed:30699359"
FT MUTAGEN 938
FT /note="S->A: Impaired phosphorylation by CK2 and
FT interaction with HSP90AA1/Hsp90."
FT /evidence="ECO:0000269|PubMed:30699359"
FT MUTAGEN 982
FT /note="K->R: No effect on ubiquitination and protein
FT stability."
FT /evidence="ECO:0000269|PubMed:30699359"
FT MUTAGEN 1117
FT /note="K->R: No effect on ubiquitination and protein
FT stability."
FT /evidence="ECO:0000269|PubMed:30699359"
FT MUTAGEN 1119
FT /note="K->R: Impaired ubiquitination, leading to increased
FT stability."
FT /evidence="ECO:0000269|PubMed:30699359"
FT MUTAGEN 1134
FT /note="K->R: No effect on ubiquitination and protein
FT stability."
FT /evidence="ECO:0000269|PubMed:30699359"
SQ SEQUENCE 1166 AA; 130555 MW; 3B99DBA98E7169C5 CRC64;
MAPTLFQKLF SKRTGLGAPG RDARDPDCGF SWPLPEFDPS QIRLIVYQDC ERRGRNVLFD
SSVKRRNEDI SVSKLGSDAQ VKVFGKCCQL KPGGDSSSSL DSSVTSSSDI KDQCLKYQGS
RCSSDANMLG EMMFGSVAMS YKGSTLKIHQ IRSPPQLMLS KVFTARTGSS ICGSLNTLQD
SLEFINQDNN TLKADNNTVI NGLLGNIGLS QFCSPRRAFS EQGPLRLIRS ASFFAVHSNP
MDMPGRELNE DRDSGIARSA SLSSLLITPF PSPNSSLTRS CASSYQRRWR RSQTTSLENG
VFPRWSIEES FNLSDESCGP NPGIVRKKKI AIGVIFSLSK DEDENNKFNE FFFSHFPLFE
SHMNKLKSAI EQAMKMSRRS ADASQRSLAY NRIVDALNEF RTTICNLYTM PRIGEPVWLT
MMSGTPEKNH LCYRFMKEFT FLMENASKNQ FLPALITAVL TNHLAWVPTV MPNGQPPIKI
FLEKHSSQSV DMLAKTHPYN PLWAQLGDLY GAIGSPVRLA RTVVVGKRQD MVQRLLYFLT
YFIRCSELQE THLLENGEDE AIVMPGTVIT TTLEKGEIEE SEYVLVTMHR NKSSLLFKES
EEIRTPNCNC KYCSHPLLGQ NVENISQQER EDIQNSSKEL LGISDECQMI SPSDCQEENA
VDVKQYRDKL RTCFDAKLET VVCTGSVPVD KCALSESGLE STEETWQSEK LLDSDSHTGK
AMRSTGMVVE KKPPDKIVPA SFSCEAAQTK VTFLIGDSMS PDSDTELRSQ AVVDQITRHH
TKPLKEERGA IDQHQETKQT TKDQSGESDT QNMVSEEPCE LPCWNHSDPE SMSLFDEYFN
DDSIETRTID DVPFKTSTDS KDHCCMLEFS KILCTKNNKQ NNEFCKCIET VPQDSCKTCF
PQQDQRDTLS ILVPHGDKES SDKKIAVGTE WDIPRNESSD SALGDSESED TGHDMTRQVS
SYYGGEQEDW AEEDEIPFPG SKLIEVSAVQ PNIANFGRSL LGGYCSSYVP DFVLQGIGSD
ERFRQCLMSD LSHAVQHPVL DEPIAEAVCI IADMDKWTVQ VASSQRRVTD NKLGKEVLVS
SLVSNLLHST LQLYKHNLSP NFCVMHLEDR LQELYFKSKM LSEYLRGQMR VHVKELGVVL
GIESSDLPLL AAVASTHSPY VAQILL
