FNIP2_MOUSE
ID FNIP2_MOUSE Reviewed; 1108 AA.
AC Q80TD3;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Folliculin-interacting protein 2 {ECO:0000303|PubMed:25775561};
DE AltName: Full=O6-methylguanine-induced apoptosis 1 protein {ECO:0000303|PubMed:19137017};
GN Name=Fnip2 {ECO:0000303|PubMed:25775561, ECO:0000312|MGI:MGI:2683054};
GN Synonyms=Kiaa1450 {ECO:0000303|PubMed:12693553},
GN Mapo1 {ECO:0000303|PubMed:19137017};
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 GENOMIC DNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 284-1108.
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION BY
RP 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 [4]
RP FUNCTION, AND 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-721 AND SER-723, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [8]
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).
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). Together with FLCN, regulates autophagy:
CC following phosphorylation by ULK1, interacts with GABARAP and promotes
CC autophagy (By similarity). In addition to its role in mTORC1 signaling,
CC also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase
CC activity of HSP90AA1/Hsp90, leading to activate both kinase and non-
CC kinase client proteins of HSP90AA1/Hsp90 (By similarity). Acts as a
CC 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). May play
CC a role in the signal transduction pathway of apoptosis induced by O6-
CC methylguanine-mispaired lesions (PubMed:19137017).
CC {ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:19137017,
CC ECO:0000269|PubMed:23582324}.
CC -!- SUBUNIT: Homodimer and homomultimer. Heterodimer and heteromultimer
CC with FNIP1. Interacts (via C-terminus) with FLCN (via C-terminus).
CC Phosphorylated FLCN is preferentially bound. 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. Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-
CC AMP-activated protein kinase. Interacts with HSP70, HSP90AA1, STIP1,
CC PTGES3, CDC37, BRAF, GCR and CDK4. {ECO:0000250|UniProtKB:Q9P278}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9P278}.
CC Cytoplasm {ECO:0000269|PubMed:19137017}. Note=Colocalizes with FLCN in
CC the cytoplasm. {ECO:0000250|UniProtKB:Q9P278}.
CC -!- PTM: Phosphorylated by AMPK. {ECO:0000250|UniProtKB:Q9P278}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking both Fnip1 and Fnip2 show enlarged
CC polycystic kidneys. {ECO:0000269|PubMed:25775561}.
CC -!- SIMILARITY: Belongs to the FNIP family. {ECO:0000305}.
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DR EMBL; AC113945; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC142502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK122512; BAC65794.1; -; mRNA.
DR CCDS; CCDS50934.1; -.
DR RefSeq; NP_001156471.1; NM_001162999.2.
DR AlphaFoldDB; Q80TD3; -.
DR SMR; Q80TD3; -.
DR STRING; 10090.ENSMUSP00000115275; -.
DR iPTMnet; Q80TD3; -.
DR PhosphoSitePlus; Q80TD3; -.
DR MaxQB; Q80TD3; -.
DR PaxDb; Q80TD3; -.
DR PRIDE; Q80TD3; -.
DR ProteomicsDB; 267610; -.
DR Antibodypedia; 28193; 161 antibodies from 26 providers.
DR Ensembl; ENSMUST00000076136; ENSMUSP00000075497; ENSMUSG00000061175.
DR GeneID; 329679; -.
DR KEGG; mmu:329679; -.
DR UCSC; uc012cqp.1; mouse.
DR CTD; 57600; -.
DR MGI; MGI:2683054; Fnip2.
DR VEuPathDB; HostDB:ENSMUSG00000061175; -.
DR eggNOG; KOG3693; Eukaryota.
DR GeneTree; ENSGT00390000009391; -.
DR InParanoid; Q80TD3; -.
DR OrthoDB; 303571at2759; -.
DR PhylomeDB; Q80TD3; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 329679; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Fnip2; mouse.
DR PRO; PR:Q80TD3; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q80TD3; protein.
DR Bgee; ENSMUSG00000061175; Expressed in decidua and 217 other tissues.
DR ExpressionAtlas; Q80TD3; baseline and differential.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042030; F:ATPase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS: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 Cytoplasm; DNA damage; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1108
FT /note="Folliculin-interacting protein 2"
FT /id="PRO_0000320554"
FT DOMAIN 38..456
FT /note="uDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 464..1034
FT /note="cDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT DOMAIN 1044..1099
FT /note="dDENN FNIP1/2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01180"
FT REGION 89..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 540..905
FT /note="Interaction with PRKAA1"
FT /evidence="ECO:0000250|UniProtKB:Q9P278"
FT REGION 598..635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 649..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 605..619
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P278"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P278"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P278"
FT MOD_RES 721
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
SQ SEQUENCE 1108 AA; 122520 MW; 4B54789BF8D3357A CRC64;
MAPTLLQKLF NKRGGGAASA QARPPKEEPA FSWSCSEFGL SDIRLLVYQD CERRGRQVMF
DSRAVQKMEE AAAQKAEDVP IKMSARCCQE SSSSSGSSSS GSSSSHGFGG SLQHAKQQLP
KYQYTRPASD VSMLGEMMFG SVAMSYKGST LKIHYIRSPP QLMISKVFSA TMGSFCGSTN
NLQDSFEYIN QDPQAGKLNT NQYNLGPFRT GSNLAHSTPV DMPSRGQNED RDSGIARSAS
LSSLLITPFP SPSSSTSSSS SYQRRWLRSQ TTSLENGIFP RRSTDETFSL AEETCSSNPA
MVRRKKIAIS IIFSLCEREA AQRDFQDFFF SHFPLFESHM NRLKGAIEKA MISCRKISES
SLRVQFYVSR LMEALGEFRG TIWNLYSVPR IAEPVWLTMM SNTLEKNQLC QRFLKEFILL
IEQVNKNQFF AALLTAVLTY HLAWVPTVMP VDHPPIKAFS EKRTSQSVNM LAKTHPYNPL
WAQLGDLYGA IGSPVRLTRT VVIGKQKDLV QRILYVLTYF LRCSELQENQ LSWSGNPSED
DQVINGSKII TALEKGEVEE SEYVVVTVSS EPALVPPILP QGTAERRSPE PTVVAEISEG
VNTSELGHKP EKNRCKRPEQ NSEASSMGFQ EAEPDSSWIP QGIFCEDKQN DQEATQDCSS
SPPSCEVPRV RRRMDQQTLH SKLHGETLKK RAEQSAAWPC PDRHSQEDPP VEKVTFHIGS
SISPESDFES RTKRMEERLK ACGHFHGASA SASSSMDTGL TQEQQGSGCS FKADFEKDIT
PQDHSSGGEG VSEDRGLRAN MTHAVGQLSQ VDGPLAHSLC AAESGRRLLE QTRDVQLKGY
KGPSSEPVPN RCRQQGGLLI AADVPYGDAS GKGNYRSEGD IPRNESLDSA LGDSDDEACV
LALLELGHSC DRTEESLEVE LPLPRSQSTS KANVRNFGRS LLAGYCATYM PDLVLHGTSS
DEKLKQCLAA DLVHTVHHPV LDEPIAEAVC IIADTDKWTV QVATSQRKVT DTMKLGQDVL
VSSQVSSLLQ SILQLYKLHL PADFCIMHLE DRLQEMYLKS KMLSEYLRGH TRVHVKELSV
VLGIESNDLP LLTAIASTHS PYVAQILL
