ID   FNIP2_HUMAN             Reviewed;        1114 AA.
AC   Q9P278; Q05DC3; Q96I31; Q9H994;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 2.
DT   24-JAN-2024, entry version 141.
DE   RecName: Full=Folliculin-interacting protein 2 {ECO:0000303|PubMed:18663353};
DE   AltName: Full=FNIP1-like protein {ECO:0000303|PubMed:18663353};
DE   AltName: Full=O6-methylguanine-induced apoptosis 1 protein {ECO:0000303|PubMed:19137017};
GN   Name=FNIP2 {ECO:0000303|PubMed:18663353, ECO:0000312|HGNC:HGNC:29280};
GN   Synonyms=FNIPL {ECO:0000303|PubMed:18663353}, KIAA1450
GN   {ECO:0000303|PubMed:10819331}, MAPO1 {ECO:0000303|PubMed:19137017};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVII. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:143-150(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-650 (ISOFORM 2), AND NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 787-983 (ISOFORM 1).
RC   TISSUE=Lymph, and Uterus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 663-1114 (ISOFORM 1).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   FUNCTION, SUBUNIT, INTERACTION WITH FLCN; PRKAA1; PRKAB1 AND PRKAG1,
RP   SUBCELLULAR LOCATION, 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   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FLCN AND PRKAA1, TISSUE
RP   SPECIFICITY, AND PHOSPHORYLATION.
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   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=19137017; DOI=10.1038/onc.2008.462;
RA   Komori K., Takagi Y., Sanada M., Lim T.H., Nakatsu Y., Tsuzuki T.,
RA   Sekiguchi M., Hidaka M.;
RT   "A novel protein, MAPO1, that functions in apoptosis triggered by O6-
RT   methylguanine mispair in DNA.";
RL   Oncogene 28:1142-1150(2009).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723 AND SER-726, 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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216 AND SER-221, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [9]
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   [10]
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   [11] {ECO:0007744|PDB:6ULG}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.31 ANGSTROMS) IN COMPLEX WITH FLCN
RP   RRAGA; RRAGC; LAMTOR1; LAMTOR2; LAMTOR3; LAMTOR4 AND LAMTOR5, AND
RP   IDENTIFICATION IN THE LFC COMPLEX.
RX   PubMed=31704029; DOI=10.1016/j.cell.2019.10.036;
RA   Shen K., Rogala K.B., Chou H.T., Huang R.K., Yu Z., Sabatini D.M.;
RT   "Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.";
RL   Cell 179:1319-1329(2019).
RN   [12] {ECO:0007744|PDB:6NZD}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH FLCN;
RP   RRAGA; RRAGC; LAMTOR1; LAMTOR2; LAMTOR3; LAMTOR4 AND LAMTOR5,
RP   IDENTIFICATION IN THE LFC COMPLEX, AND FUNCTION.
RX   PubMed=31672913; DOI=10.1126/science.aax0364;
RA   Lawrence R.E., Fromm S.A., Fu Y., Yokom A.L., Kim D.J., Thelen A.M.,
RA   Young L.N., Lim C.Y., Samelson A.J., Hurley J.H., Zoncu R.;
RT   "Structural mechanism of a Rag GTPase activation checkpoint by the
RT   lysosomal folliculin complex.";
RL   Science 366:971-977(2019).
RN   [13] {ECO:0007744|PDB:8DHB}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.53 ANGSTROMS) IN COMPLEX WITH RRAGA;
RP   RRAGC; LAMTOR1; LAMTOR2; LAMTOR3; LAMTOR4; LAMTOR5; FLCN AND SLC38A9,
RP   FUNCTION, AND MUTAGENESIS OF VAL-146.
RX   PubMed=36103527; DOI=10.1126/sciadv.add2926;
RA   Jansen R.M., Peruzzo R., Fromm S.A., Yokom A.L., Zoncu R., Hurley J.H.;
RT   "Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-
RT   selective mTORC1 regulation.";
RL   Sci. Adv. 8:eadd2926-eadd2926(2022).
CC   -!- FUNCTION: Binding partner of the GTPase-activating protein FLCN:
CC       involved in the cellular response to amino acid availability by
CC       regulating the non-canonical mTORC1 signaling cascade controlling the
CC       MiT/TFE factors TFEB and TFE3 (PubMed:18663353, PubMed:31672913,
CC       PubMed:36103527). Required to promote FLCN recruitment to lysosomes and
CC       interaction with Rag GTPases, leading to activation of the non-
CC       canonical mTORC1 signaling (By similarity). In low-amino acid
CC       conditions, component of the lysosomal folliculin complex (LFC) on the
CC       membrane of lysosomes, which inhibits the GTPase-activating activity of
CC       FLCN, thereby inactivating mTORC1 and promoting nuclear translocation
CC       of TFEB and TFE3 (PubMed:31672913, PubMed:36103527). 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 inactivation of TFEB and TFE3 (PubMed:31672913). Together
CC       with FLCN, regulates autophagy: following phosphorylation by ULK1,
CC       interacts with GABARAP and promotes autophagy (PubMed:25126726). In
CC       addition to its role in mTORC1 signaling, also acts as a co-chaperone
CC       of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90,
CC       leading to activate both kinase and non-kinase client proteins of
CC       HSP90AA1/Hsp90 (PubMed:18403135). Acts as a scaffold to load client
CC       protein FLCN onto HSP90AA1/Hsp90 (PubMed:18403135). Competes with the
CC       activating co-chaperone AHSA1 for binding to HSP90AA1, thereby
CC       providing a reciprocal regulatory mechanism for chaperoning of client
CC       proteins (PubMed:18403135). May play a role in the signal transduction
CC       pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By
CC       similarity). {ECO:0000250|UniProtKB:Q80TD3,
CC       ECO:0000250|UniProtKB:Q8TF40, ECO:0000269|PubMed:18403135,
CC       ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:25126726,
CC       ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:36103527}.
CC   -!- SUBUNIT: Homodimer and homomultimer (PubMed:18403135, PubMed:27353360).
CC       Heterodimer and heteromultimer with FNIP1 (PubMed:18403135,
CC       PubMed:27353360). Interacts (via C-terminus) with FLCN (via C-terminus)
CC       (PubMed:18403135, PubMed:18663353, PubMed:27353360, PubMed:36103527).
CC       Phosphorylated FLCN is preferentially bound (PubMed:18663353).
CC       Component of the lysosomal folliculin complex (LFC), composed of FLCN,
CC       FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or
CC       RagD/RRAGD GTP-bound, and Ragulator (PubMed:31704029, PubMed:31672913,
CC       PubMed:36103527). Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of
CC       5'-AMP-activated protein kinase (PubMed:18403135, PubMed:27353360).
CC       Interacts with HSP70, HSP90AA1, STIP1, PTGES3, CDC37, BRAF, GCR and
CC       CDK4 (PubMed:27353360). {ECO:0000269|PubMed:18403135,
CC       ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:27353360,
CC       ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:31704029,
CC       ECO:0000269|PubMed:36103527}.
CC   -!- INTERACTION:
CC       Q9P278; Q8NFG4: FLCN; NbExp=7; IntAct=EBI-7597109, EBI-2970160;
CC       Q9P278; Q8TF40: FNIP1; NbExp=7; IntAct=EBI-7597109, EBI-2946919;
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000305|PubMed:31672913}.
CC       Cytoplasm {ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353,
CC       ECO:0000269|PubMed:19137017}. Note=Colocalizes with FLCN in the
CC       cytoplasm. {ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9P278-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9P278-2; Sequence=VSP_031656;
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in muscle,
CC       nasal mucosa, salivary gland, uvula, fat, liver, heart, placenta and
CC       pancreas (PubMed:18403135, PubMed:18663353, PubMed:27353360).
CC       Moderately expressed in the lung, small intestine, kidney and brain.
CC       Lower levels detected in renal cell carcinoma than in normal kidney
CC       tissue (PubMed:18403135). Higher levels detected in oncocytoma tumors
CC       than in normal kidney. Higher levels detected in renal cell carcinoma
CC       tumors than in normal kidney tissue (PubMed:27353360).
CC       {ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353,
CC       ECO:0000269|PubMed:27353360}.
CC   -!- PTM: Phosphorylated by AMPK. {ECO:0000269|PubMed:18663353}.
CC   -!- SIMILARITY: Belongs to the FNIP family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH07861.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAH16638.1; Type=Miscellaneous discrepancy; Note=Potential poly-A sequence.; Evidence={ECO:0000305};
CC       Sequence=BAA95974.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAB14338.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB040883; BAA95974.1; ALT_INIT; mRNA.
DR   EMBL; BC007861; AAH07861.1; ALT_INIT; mRNA.
DR   EMBL; BC016638; AAH16638.1; ALT_SEQ; mRNA.
DR   EMBL; AK022968; BAB14338.1; ALT_INIT; mRNA.
DR   CCDS; CCDS47155.1; -. [Q9P278-1]
DR   RefSeq; NP_001310845.1; NM_001323916.1. [Q9P278-2]
DR   RefSeq; NP_001332972.1; NM_001346043.1.
DR   RefSeq; NP_065891.1; NM_020840.2. [Q9P278-1]
DR   PDB; 6NZD; EM; 3.60 A; I=1-1114.
DR   PDB; 6ULG; EM; 3.31 A; N=1-1114.
DR   PDB; 7LSW; X-ray; 3.05 A; A/B/C/D/E/F=552-576.
DR   PDB; 7LT6; X-ray; 1.80 A; A/B/C=558-576.
DR   PDB; 8DHB; EM; 3.53 A; I=1-1114.
DR   PDBsum; 6NZD; -.
DR   PDBsum; 6ULG; -.
DR   PDBsum; 7LSW; -.
DR   PDBsum; 7LT6; -.
DR   PDBsum; 8DHB; -.
DR   AlphaFoldDB; Q9P278; -.
DR   EMDB; EMD-0554; -.
DR   EMDB; EMD-20814; -.
DR   EMDB; EMD-27435; -.
DR   SMR; Q9P278; -.
DR   BioGRID; 121650; 21.
DR   ComplexPortal; CPX-2440; FLCN-FNIP GTPase-activating complex, FNIP2 variant.
DR   CORUM; Q9P278; -.
DR   IntAct; Q9P278; 7.
DR   MINT; Q9P278; -.
DR   STRING; 9606.ENSP00000264433; -.
DR   iPTMnet; Q9P278; -.
DR   PhosphoSitePlus; Q9P278; -.
DR   BioMuta; FNIP2; -.
DR   DMDM; 189035874; -.
DR   EPD; Q9P278; -.
DR   jPOST; Q9P278; -.
DR   MassIVE; Q9P278; -.
DR   MaxQB; Q9P278; -.
DR   PaxDb; 9606-ENSP00000264433; -.
DR   PeptideAtlas; Q9P278; -.
DR   ProteomicsDB; 83745; -. [Q9P278-1]
DR   ProteomicsDB; 83746; -. [Q9P278-2]
DR   Antibodypedia; 28193; 178 antibodies from 26 providers.
DR   DNASU; 57600; -.
DR   Ensembl; ENST00000264433.11; ENSP00000264433.6; ENSG00000052795.13. [Q9P278-1]
DR   GeneID; 57600; -.
DR   KEGG; hsa:57600; -.
DR   MANE-Select; ENST00000264433.11; ENSP00000264433.6; NM_020840.3; NP_065891.1.
DR   UCSC; uc003iqe.5; human. [Q9P278-1]
DR   AGR; HGNC:29280; -.
DR   CTD; 57600; -.
DR   DisGeNET; 57600; -.
DR   GeneCards; FNIP2; -.
DR   HGNC; HGNC:29280; FNIP2.
DR   HPA; ENSG00000052795; Low tissue specificity.
DR   MIM; 612768; gene.
DR   neXtProt; NX_Q9P278; -.
DR   OpenTargets; ENSG00000052795; -.
DR   PharmGKB; PA162388758; -.
DR   VEuPathDB; HostDB:ENSG00000052795; -.
DR   eggNOG; KOG3693; Eukaryota.
DR   GeneTree; ENSGT00390000009391; -.
DR   HOGENOM; CLU_003447_0_0_1; -.
DR   InParanoid; Q9P278; -.
DR   OMA; IADTDKC; -.
DR   OrthoDB; 2725349at2759; -.
DR   PhylomeDB; Q9P278; -.
DR   TreeFam; TF324090; -.
DR   PathwayCommons; Q9P278; -.
DR   Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR   SignaLink; Q9P278; -.
DR   SIGNOR; Q9P278; -.
DR   BioGRID-ORCS; 57600; 6 hits in 1156 CRISPR screens.
DR   ChiTaRS; FNIP2; human.
DR   GenomeRNAi; 57600; -.
DR   Pharos; Q9P278; Tbio.
DR   PRO; PR:Q9P278; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q9P278; Protein.
DR   Bgee; ENSG00000052795; Expressed in kidney epithelium and 197 other cell types or tissues.
DR   ExpressionAtlas; Q9P278; baseline and differential.
DR   GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:1990877; C:FNIP-folliculin RagC/D GAP; IDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042030; F:ATPase inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0051087; F:protein-folding chaperone binding; IDA:UniProtKB.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR   GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IDA: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   PANTHER; PTHR21634:SF11; FOLLICULIN-INTERACTING PROTEIN 2; 1.
DR   PANTHER; PTHR21634; UNCHARACTERIZED; 1.
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.
DR   Genevisible; Q9P278; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; DNA damage; Lysosome;
KW   Membrane; Phosphoprotein; Reference proteome.
FT   CHAIN           1..1114
FT                   /note="Folliculin-interacting protein 2"
FT                   /id="PRO_0000320553"
FT   DOMAIN          42..460
FT                   /note="uDENN FNIP1/2-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT   DOMAIN          468..1040
FT                   /note="cDENN FNIP1/2-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT   DOMAIN          1050..1105
FT                   /note="dDENN FNIP1/2-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT   REGION          12..32
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          93..126
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          203..237
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          544..911
FT                   /note="Interaction with PRKAA1"
FT                   /evidence="ECO:0000269|PubMed:18663353"
FT   REGION          585..632
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          645..665
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          747..800
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          875..900
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        93..118
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        203..228
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        606..623
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        785..800
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         216
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         221
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         723
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         726
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   VAR_SEQ         1..35
FT                   /note="MAPTLLQKLFNKRGSSGSSAAASAQGRAPKEGPAF -> MCGGTANTTNQPE
FT                   SWQDSARCVSDAVPGAGRIYRALLCTKIKKHTGVDRSTDHTELDN (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_031656"
FT   VARIANT         298
FT                   /note="T -> S (in dbSNP:rs2276938)"
FT                   /id="VAR_045612"
FT   MUTAGEN         146
FT                   /note="V->D: Abolished GTPase activation (GAP) activity of
FT                   FLCN."
FT                   /evidence="ECO:0000269|PubMed:36103527"
FT   STRAND          50..54
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          56..58
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          61..64
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          66..68
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           135..143
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          155..158
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   TURN            161..164
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          167..175
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   TURN            176..178
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          179..182
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          308..317
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           323..333
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           337..359
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           365..390
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           399..405
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           412..427
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          430..433
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           434..443
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           485..491
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          496..498
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          503..506
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           513..521
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           522..524
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          532..535
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          553..559
FT                   /evidence="ECO:0007829|PDB:7LSW"
FT   STRAND          561..563
FT                   /evidence="ECO:0007829|PDB:7LT6"
FT   STRAND          568..572
FT                   /evidence="ECO:0007829|PDB:7LT6"
FT   HELIX           975..986
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          989..992
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          999..1002
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          1007..1010
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          1012..1014
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           1029..1043
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           1050..1071
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   STRAND          1074..1076
FT                   /evidence="ECO:0007829|PDB:6ULG"
FT   HELIX           1097..1102
FT                   /evidence="ECO:0007829|PDB:6ULG"
SQ   SEQUENCE   1114 AA;  122115 MW;  8951340C11EE0D5B CRC64;
     MAPTLLQKLF NKRGSSGSSA AASAQGRAPK EGPAFSWSCS EFDLNEIRLI VYQDCDRRGR
     QVLFDSKAVQ KIEEVTAQKT EDVPIKISAK CCQGSSSVSS SSSSSISSHS SSGGSSHHAK
     EQLPKYQYTR PASDVNMLGE MMFGSVAMSY KGSTLKIHYI RSPPQLMISK VFSARMGSFC
     GSTNNLQDSF EYINQDPNLG KLNTNQNSLG PCRTGSNLAH STPVDMPSRG QNEDRDSGIA
     RSASLSSLLI TPFPSPSSST SSSSSYQRRW LRSQTTSLEN GIIPRRSTDE TFSLAEETCS
     SNPAMVRRKK IAISIIFSLC EKEEAQRNFQ DFFFSHFPLF ESHMNRLKSA IEKAMISCRK
     IAESSLRVQF YVSRLMEALG EFRGTIWNLY SVPRIAEPVW LTMMSGTLEK NQLCQRFLKE
     FTLLIEQINK NQFFAALLTA VLTYHLAWVP TVMPVDHPPI KAFSEKRTSQ SVNMLAKTHP
     YNPLWAQLGD LYGAIGSPVR LTRTVVVGKQ KDLVQRILYV LTYFLRCSEL QENQLTWSGN
     HGEGDQVLNG SKIITALEKG EVEESEYVVI TVRNEPALVP PILPPTAAER HNPWPTGFPE
     CPEGTDSRDL GLKPDKEANR RPEQGSEACS AGCLGPASDA SWKPQNAFCG DEKNKEAPQD
     GSSRLPSCEV LGAGMKMDQQ AVCELLKVEM PTRLPDRSVA WPCPDRHLRE KPSLEKVTFQ
     IGSFASPESD FESRMKKMEE RVKACGPSLE ASEAADVAQD PQVSRSPFKP GFQENVCCPQ
     NRLSEGDEGE SDKGFAEDRG SRNDMAADIA GQLSHAADLG TASHGAGGTG GRRLEATRGL
     YVKAAEGPVL EPVAPRCVQR GPGLVAGANI PCGDDNKKAN FRTEGDIPRN ESSDSALGDS
     DDEACASAML DLGHGGDRTG GSLEVELPLP RSQSISTQNV RNFGRSLLAG YCPTYMPDLV
     LHGTGSDEKL KQCLVADLVH TVHHPVLDEP IAEAVCIIAD TDKWSVQVAT SQRKVTDNMK
     LGQDVLVSSQ VSSLLQSILQ LYKLHLPADF CIMHLEDRLQ EMYLKSKMLS EYLRGHTRVH
     VKELGVVLGI ESNDLPLLTA IASTHSPYVA QILL
//