ID FXR2_MOUSE Reviewed; 673 AA. AC Q9WVR4; Q9WVR5; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 145. DE RecName: Full=RNA-binding protein FXR2 {ECO:0000305}; DE Short=FXR2P {ECO:0000303|PubMed:11438699}; GN Name=Fxr2 {ECO:0000303|PubMed:10524236, ECO:0000312|MGI:MGI:1346074}; GN Synonyms=Fxr2h {ECO:0000303|PubMed:10524236}; 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 [GENOMIC DNA / MRNA]. RC STRAIN=129; RX PubMed=10524236; DOI=10.1016/s0378-1119(99)00301-7; RA Miyashita A., Shimizu N., Endo N., Hanyuu T., Ishii N., Ito K., Itoh Y., RA Shirai M., Nakajima T., Odani S., Kuwano R.; RT "Five different genes, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are RT clustered in a 40 kb region of mouse chromosome 11."; RL Gene 237:53-60(1999). RN [2] RP INTERACTION WITH CYFIP2. RX PubMed=11438699; DOI=10.1073/pnas.151231598; RA Schenck A., Bardoni B., Moro A., Bagni C., Mandel J.-L.; RT "A highly conserved protein family interacting with the fragile X mental RT retardation protein (FMRP) and displaying selective interactions with FMRP- RT related proteins FXR1P and FXR2P."; RL Proc. Natl. Acad. Sci. U.S.A. 98:8844-8849(2001). RN [3] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=11875043; DOI=10.1093/hmg/11.5.487; RA Bontekoe C.J., McIlwain K.L., Nieuwenhuizen I.M., Yuva-Paylor L.A., RA Nellis A., Willemsen R., Fang Z., Kirkpatrick L., Bakker C.E., McAninch R., RA Cheng N.C., Merriweather M., Hoogeveen A.T., Nelson D., Paylor R., RA Oostra B.A.; RT "Knockout mouse model for Fxr2: a model for mental retardation."; RL Hum. Mol. Genet. 11:487-498(2002). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [5] RP DISRUPTION PHENOTYPE. RX PubMed=16675531; DOI=10.1093/hmg/ddl121; RA Spencer C.M., Serysheva E., Yuva-Paylor L.A., Oostra B.A., Nelson D.L., RA Paylor R.; RT "Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal RT a functional genetic interaction between Fragile X-related proteins."; RL Hum. Mol. Genet. 15:1984-1994(2006). 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 DISRUPTION PHENOTYPE. RX PubMed=18930145; DOI=10.1016/j.nbd.2008.09.008; RA Cavallaro S., Paratore S., Fradale F., de Vrij F.M., Willemsen R., RA Oostra B.A.; RT "Genes and pathways differentially expressed in the brains of Fxr2 knockout RT mice."; RL Neurobiol. Dis. 32:510-520(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-413; SER-602 AND SER-604, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and RC 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 [10] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=21658585; DOI=10.1016/j.neuron.2011.03.027; RA Guo W., Zhang L., Christopher D.M., Teng Z.Q., Fausett S.R., Liu C., RA George O.L., Klingensmith J., Jin P., Zhao X.; RT "RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by RT reducing Noggin expression."; RL Neuron 70:924-938(2011). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=27770568; DOI=10.7554/elife.20560; RA Wang G.X., Smith S.J., Mourrain P.; RT "Sub-synaptic, multiplexed analysis of proteins reveals Fragile X related RT protein 2 is mislocalized in Fmr1 KO synapses."; RL Elife 5:0-0(2016). CC -!- FUNCTION: mRNA-binding protein that acts as a regulator of mRNAs CC translation and/or stability, and which is required for adult CC hippocampal neurogenesis (PubMed:21658585). Specifically binds to AU- CC rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:21658585). CC Promotes formation of some phase-separated membraneless compartment by CC undergoing liquid-liquid phase separation upon binding to AREs- CC containing mRNAs: mRNAs storage into membraneless compartments CC regulates their translation and/or stability (By similarity). Acts as a CC regulator of adult hippocampal neurogenesis by regulating translation CC and/or stability of NOG mRNA, thereby preventing NOG protein expression CC in the dentate gyrus (PubMed:21658585). {ECO:0000250|UniProtKB:Q61584, CC ECO:0000269|PubMed:21658585}. CC -!- SUBUNIT: Interacts with FMR1 (By similarity). Interacts with FXR1 (By CC similarity). Interacts with TDRD3 (By similarity). Interacts with HABP4 CC (By similarity). Interacts with CYFIP2 but not with CYFIP1 CC (PubMed:11438699). {ECO:0000250|UniProtKB:P51116, CC ECO:0000269|PubMed:11438699}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, Cytoplasmic ribonucleoprotein granule CC {ECO:0000250|UniProtKB:Q61584}. Cytoplasm CC {ECO:0000269|PubMed:11875043}. Postsynapse CC {ECO:0000269|PubMed:27770568}. Note=Specifically localizes to CC cytoplasmic ribonucleoprotein membraneless compartments (By CC similarity). Localization to the post-synaptic region is dependent on CC FMR1 (PubMed:27770568). {ECO:0000250|UniProtKB:Q61584, CC ECO:0000269|PubMed:27770568}. CC -!- TISSUE SPECIFICITY: Highly expressed in brain and testis CC (PubMed:11875043). In brain, expressed in the subventricular zone of CC the lateral ventricles and in most of the granule neurons of the CC dentate gyrus of the hippocampus (PubMed:21658585). CC {ECO:0000269|PubMed:11875043, ECO:0000269|PubMed:21658585}. CC -!- DOMAIN: The tandem Agenet-like domains preferentially recognize CC trimethylated histone peptides. {ECO:0000250|UniProtKB:P51116}. CC -!- DOMAIN: Disordered region at the C-terminus undergoes liquid-liquid CC phase separation (LLPS) for the formation of a membraneless compartment CC that stores mRNAs. {ECO:0000250|UniProtKB:Q61584}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype; mice are viable and fertile CC and do not exhibit any overt phenotype (PubMed:11875043). Mice however CC show behavioral abnormalities, characterized by hyperactivity CC (PubMed:11875043). Increased proliferation of radial glia-like neural CC stem/progenitor cells in the adult dentate gyrus caused by increased CC Nog (Noggin) expression and subsequently reduced BMP signaling CC (PubMed:21658585). Misregulation of a number of transcripts involved in CC memory or cognitions is observed in the brain of mutant mice CC (PubMed:18930145). Mice lacking both Fxr2 and Fmr1 display exaggerated CC learning deficits, characterized by prepulse inhibition of acoustic CC startle response and contextual fear conditioning compared with single CC mutant (Fxr2 or Fmr1) mice (PubMed:16675531). CC {ECO:0000269|PubMed:11875043, ECO:0000269|PubMed:16675531, CC ECO:0000269|PubMed:18930145, ECO:0000269|PubMed:21658585}. CC -!- SIMILARITY: Belongs to the FMR1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB025269; BAA82147.1; -; mRNA. DR EMBL; AB025311; BAA82249.1; -; Genomic_DNA. DR AlphaFoldDB; Q9WVR4; -. DR SMR; Q9WVR4; -. DR IntAct; Q9WVR4; 7. DR MINT; Q9WVR4; -. DR STRING; 10090.ENSMUSP00000018909; -. DR GlyGen; Q9WVR4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9WVR4; -. DR PhosphoSitePlus; Q9WVR4; -. DR EPD; Q9WVR4; -. DR jPOST; Q9WVR4; -. DR MaxQB; Q9WVR4; -. DR PaxDb; 10090-ENSMUSP00000018909; -. DR PeptideAtlas; Q9WVR4; -. DR ProteomicsDB; 266892; -. DR Pumba; Q9WVR4; -. DR AGR; MGI:1346074; -. DR MGI; MGI:1346074; Fxr2. DR eggNOG; ENOG502QPKJ; Eukaryota. DR InParanoid; Q9WVR4; -. DR ChiTaRS; Fxr2; mouse. DR PRO; PR:Q9WVR4; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q9WVR4; Protein. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IBA:GO_Central. DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0030425; C:dendrite; IDA:MGI. DR GO; GO:1902737; C:dendritic filopodium; IBA:GO_Central. DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central. DR GO; GO:0044326; C:dendritic spine neck; IBA:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0030426; C:growth cone; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005844; C:polysome; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0098793; C:presynapse; IBA:GO_Central. DR GO; GO:0005840; C:ribosome; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0045182; F:translation regulator activity; IBA:GO_Central. DR GO; GO:0021542; P:dentate gyrus development; IMP:UniProtKB. DR GO; GO:0061157; P:mRNA destabilization; IMP:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; IBA:GO_Central. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central. DR GO; GO:0045727; P:positive regulation of translation; IBA:GO_Central. DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IBA:GO_Central. DR GO; GO:0051489; P:regulation of filopodium assembly; IBA:GO_Central. DR GO; GO:0043488; P:regulation of mRNA stability; IBA:GO_Central. DR CDD; cd22505; KH_I_FXR2_rpt1; 1. DR CDD; cd22508; KH_I_FXR2_rpt2; 1. DR CDD; cd20473; Tudor_Agenet_FXR2_rpt1; 1. DR CDD; cd20476; Tudor_Agenet_FXR2_rpt2; 1. DR Gene3D; 2.30.30.140; -; 2. DR Gene3D; 3.30.1370.10; K Homology domain, type 1; 2. DR InterPro; IPR008395; Agenet-like_dom. DR InterPro; IPR040148; FMR1. DR InterPro; IPR022034; FMR1-like_C_core. DR InterPro; IPR040472; FMRP_KH0. DR InterPro; IPR032172; FXR1_C1. DR InterPro; IPR004087; KH_dom. DR InterPro; IPR004088; KH_dom_type_1. DR InterPro; IPR036612; KH_dom_type_1_sf. DR InterPro; IPR047422; KH_I_FXR2_rpt1. DR InterPro; IPR047424; KH_I_FXR2_rpt2. DR InterPro; IPR047421; Tudor_Agenet_FXR2_rpt1. DR InterPro; IPR047420; Tudor_Agenet_FXR2_rpt2. DR InterPro; IPR041560; Tudor_FRM1. DR PANTHER; PTHR10603; FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN; 1. DR PANTHER; PTHR10603:SF3; FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN 2; 1. DR Pfam; PF05641; Agenet; 1. DR Pfam; PF12235; FXMRP1_C_core; 1. DR Pfam; PF16096; FXR_C1; 1. DR Pfam; PF00013; KH_1; 2. DR Pfam; PF17904; KH_9; 1. DR Pfam; PF18336; Tudor_FRX1; 1. DR SMART; SM00322; KH; 2. DR SUPFAM; SSF54791; Eukaryotic type KH-domain (KH-domain type I); 2. DR PROSITE; PS51641; AGENET_LIKE; 2. DR PROSITE; PS50084; KH_TYPE_1; 2. PE 1: Evidence at protein level; KW Cytoplasm; Phosphoprotein; Reference proteome; Repeat; RNA-binding; KW Synapse. FT CHAIN 1..673 FT /note="RNA-binding protein FXR2" FT /id="PRO_0000050111" FT DOMAIN 14..60 FT /note="Agenet-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00973" FT DOMAIN 73..125 FT /note="Agenet-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00973" FT DOMAIN 228..276 FT /note="KH 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117" FT DOMAIN 291..340 FT /note="KH 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117" FT REGION 388..673 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 409..427 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 455..488 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 501..524 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 615..644 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 78 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q61584" FT MOD_RES 192 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 413 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 452 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61584" FT MOD_RES 455 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61584" FT MOD_RES 534 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 567 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 581 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 599 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P51116" FT MOD_RES 602 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 604 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" SQ SEQUENCE 673 AA; 73743 MW; 01F6814D4C3B5654 CRC64; MGGLASGGDV EPGLPVEVRG SNGAFYKGFV KDVHEDSVTI FFENNWQSER QIPFGDVRLP PPADYNKEIT EGDEVEVYSR ANEQEPCGWC LARVRMMKGD FYVIEYAACD ATYNEIVTLE RLRPVNSSSL ATKGSFFKVT MAVPEDLREA CSNENVHKEF KKALGANCIF LNITNSELFI LSTTEAPVKR ASLLGDMHFR SLRTKLLLMS RNEEATKHLE TSKQLAAAFQ EEFTVREDLM GLAIGTHGAN IQQARKVPGV TAIELGEETC TFRIYGETPE ACRQARSYLE FSEDSVQVPR DLVGKVTGKT GKVIQGIVDK SGVVRVRVEG DNDKKNPKEG GMVPFIFVGT RENISNAQAL LEYHLSYLQE VETLRLERLQ IDEQLRQIGA GFRPPGSGRG GSGGGSDKAG YTTDESSSSS LHTTRTYGGS YGGRGRGRRT GGPAYGPSSD PSTASETESE KREESNRAGP GDRDPPSRGE ESRRRRLGPG KGPPPVPRPT SRYNSSSISS VLKDPDSNPY SLLDTSEPEP PVDSEPGEPP PASARRRRSR RRRTDEDRTV MDGALESDGP NMTENGLEDE SRPQRRNRSR RRRNRGNRTD GSISGDRQPV TVADYISRAE SQSRQRPLGR TEPSEDSLSG QKGDSVSKLP KGPSENGELS APLELGSLVN GVS //