ID FXR1_RAT Reviewed; 568 AA.
AC Q5XI81;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 27-MAR-2024, entry version 124.
DE RecName: Full=RNA-binding protein FXR1 {ECO:0000305};
DE AltName: Full=FMR1 autosomal homolog 1 {ECO:0000312|RGD:1311733};
GN Name=Fxr1 {ECO:0000312|RGD:1311733};
GN Synonyms=Fxr1h {ECO:0000312|EMBL:AAH83807.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-398; SER-432; SER-435;
RP SER-438; SER-449; SER-452; THR-512 AND SER-514, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: mRNA-binding protein that acts as a regulator of mRNAs
CC translation and/or stability, and which is required for various
CC processes, such as neurogenesis, muscle development and
CC spermatogenesis. Specifically binds to AU-rich elements (AREs) in the
CC 3'-UTR of target mRNAs. Promotes formation of some phase-separated
CC membraneless compartment by undergoing liquid-liquid phase separation
CC upon binding to AREs-containing mRNAs, leading to assemble mRNAs into
CC cytoplasmic ribonucleoprotein granules that concentrate mRNAs with
CC associated regulatory factors. Required to activate translation of
CC stored mRNAs during late spermatogenesis: acts by undergoing liquid-
CC liquid phase separation to assemble target mRNAs into cytoplasmic
CC ribonucleoprotein granules that recruit translation initiation factor
CC EIF4G3 to activate translation of stored mRNAs in late spermatids (By
CC similarity). Promotes translation of MYC transcripts by recruiting the
CC eIF4F complex to the translation start site. Acts as a negative
CC regulator of inflammation in response to IL19 by promoting
CC destabilization of pro-inflammatory transcripts (By similarity). Also
CC acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing
CC TNF protein production. Acts as a negative regulator of AMPA receptor
CC GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of
CC hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting
CC its translation. Regulates proliferation of adult neural stem cells by
CC binding to CDKN1A mRNA and promoting its expression. Acts as a
CC regulator of sleep and synaptic homeostasis by regulating translation
CC of transcripts in neurons. Required for embryonic and postnatal
CC development of muscle tissue by undergoing liquid-liquid phase
CC separation to assemble target mRNAs into cytoplasmic ribonucleoprotein
CC granules (By similarity). Involved in the nuclear pore complex
CC localization to the nuclear envelope by preventing cytoplasmic
CC aggregation of nucleoporins: acts by preventing ectopic phase
CC separation of nucleoporins in the cytoplasm via a microtubule-dependent
CC mechanism (By similarity). {ECO:0000250|UniProtKB:P51114,
CC ECO:0000250|UniProtKB:Q61584}.
CC -!- SUBUNIT: Interacts with FMR1. Interacts with FRX2. Interacts with
CC TDRD3. Interacts with HABP4 (By similarity). Interacts with CYFIP2 but
CC not with CYFIP1. Interacts with EIF4G3; promoting translation of target
CC mRNAs (By similarity). Interacts with ELAVL1. Interacts with CEP63;
CC inhibiting 'Lys-63'-linked ubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:P51114, ECO:0000250|UniProtKB:Q61584}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, Cytoplasmic ribonucleoprotein granule
CC {ECO:0000250|UniProtKB:Q61584}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:P51114}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q61584}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q61584}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q61584}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q61584}. Nucleus envelope
CC {ECO:0000250|UniProtKB:P51114}. Postsynapse
CC {ECO:0000250|UniProtKB:Q61584}. Note=Specifically localizes to
CC cytoplasmic ribonucleoprotein membraneless compartments (By
CC similarity). Localizes to stress granules following phosphorylation at
CC Ser-449 by PAK1 (By similarity). Adjacent to Z-lines in muscles (By
CC similarity). {ECO:0000250|UniProtKB:P51114,
CC ECO:0000250|UniProtKB:Q61584}.
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 -!- DOMAIN: The tandem Agenet-like domains preferentially recognize
CC trimethylated histone peptides. {ECO:0000250|UniProtKB:P51114}.
CC -!- PTM: Phosphorylation at Ser-449 by PAK1 promotes its relocalization to
CC stress granules and activity (By similarity). Phosphorylated by
CC MAPK1/ERK2, promoting subsequent phosphorylation by GSK3B.
CC Phosphorylated by GSK3B, promoting ubiquitination and degradation by
CC the proteasome (By similarity). {ECO:0000250|UniProtKB:P51114,
CC ECO:0000250|UniProtKB:Q61584}.
CC -!- PTM: Ubiquitinated by the SCF(FBXO4) complex, leading to its
CC degradation by the proteasome: ubiquitination by the SCF(FBXO4) complex
CC takes place following phosphorylation by GSK3B. Ubiquitinated and
CC degraded in a GSK3B-dependent manner in during both scaling and sleep
CC deprivation (By similarity). Ubiquitinated via 'Lys-63'-linked
CC ubiquitin, leading to its degradation: interaction with CEP63 inhibits
CC 'Lys-63'-linked ubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:P51114, ECO:0000250|UniProtKB:Q61584}.
CC -!- MISCELLANEOUS: This protein corresponds to isoform B in mouse and
CC isoform 2 in human. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the FMR1 family. {ECO:0000305}.
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DR EMBL; BC083807; AAH83807.1; -; mRNA.
DR RefSeq; NP_001012179.1; NM_001012179.2.
DR AlphaFoldDB; Q5XI81; -.
DR SMR; Q5XI81; -.
DR BioGRID; 263063; 2.
DR IntAct; Q5XI81; 4.
DR MINT; Q5XI81; -.
DR STRING; 10116.ENSRNOP00000069834; -.
DR BindingDB; Q5XI81; -.
DR iPTMnet; Q5XI81; -.
DR PhosphoSitePlus; Q5XI81; -.
DR jPOST; Q5XI81; -.
DR PaxDb; 10116-ENSRNOP00000065667; -.
DR GeneID; 361927; -.
DR KEGG; rno:361927; -.
DR UCSC; RGD:1311733; rat.
DR AGR; RGD:1311733; -.
DR CTD; 8087; -.
DR RGD; 1311733; Fxr1.
DR eggNOG; ENOG502QPKJ; Eukaryota.
DR InParanoid; Q5XI81; -.
DR OrthoDB; 2995592at2759; -.
DR PhylomeDB; Q5XI81; -.
DR PRO; PR:Q5XI81; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0043034; C:costamere; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:1902737; C:dendritic filopodium; IBA:GO_Central.
DR GO; GO:0043197; C:dendritic spine; ISO:RGD.
DR GO; GO:0044326; C:dendritic spine neck; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0030426; C:growth cone; IBA:GO_Central.
DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005844; C:polysome; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IBA:GO_Central.
DR GO; GO:0035770; C:ribonucleoprotein granule; ISO:RGD.
DR GO; GO:0005840; C:ribosome; ISO:RGD.
DR GO; GO:0140693; F:molecular condensate scaffold activity; ISS:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:1905538; F:polysome binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:RGD.
DR GO; GO:0033592; F:RNA strand annealing activity; ISS:UniProtKB.
DR GO; GO:0045182; F:translation regulator activity; IBA:GO_Central.
DR GO; GO:0021542; P:dentate gyrus development; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; ISS:UniProtKB.
DR GO; GO:0051292; P:nuclear pore complex assembly; ISS:UniProtKB.
DR GO; GO:0051664; P:nuclear pore localization; ISS:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0045727; P:positive regulation of translation; ISS:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; ISS:UniProtKB.
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 GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:0060538; P:skeletal muscle organ development; ISO:RGD.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR CDD; cd22504; KH_I_FXR1_rpt1; 1.
DR CDD; cd22507; KH_I_FXR1_rpt2; 1.
DR CDD; cd22510; KH_I_FXR1_rpt3; 1.
DR CDD; cd20472; Tudor_Agenet_FXR1_rpt1; 1.
DR CDD; cd20475; Tudor_Agenet_FXR1_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; IPR047494; KH_I_FXR1_rpt1.
DR InterPro; IPR047495; KH_I_FXR1_rpt2.
DR InterPro; IPR047496; KH_I_FXR1_rpt3.
DR InterPro; IPR047425; Tudor_Agenet_FXR1_rpt1.
DR InterPro; IPR047427; Tudor_Agenet_FXR1_rpt2.
DR InterPro; IPR041560; Tudor_FRM1.
DR PANTHER; PTHR10603; FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN; 1.
DR PANTHER; PTHR10603:SF6; FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN 1; 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 Acetylation; Cell projection; Cytoplasm; Developmental protein;
KW Differentiation; Isopeptide bond; Methylation; Myogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Spermatogenesis;
KW Synapse; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P51114"
FT CHAIN 2..568
FT /note="RNA-binding protein FXR1"
FT /id="PRO_0000248488"
FT DOMAIN 4..50
FT /note="Agenet-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00973"
FT DOMAIN 63..115
FT /note="Agenet-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00973"
FT DOMAIN 218..279
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 281..351
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 380..568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..486
FT /note="RNA-binding RGG-box"
FT /evidence="ECO:0000255"
FT COMPBIAS 438..473
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P51114"
FT MOD_RES 68
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61584"
FT MOD_RES 398
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 430
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P51114"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 476
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 476
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 482
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 482
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 484
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 484
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 512
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51116"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P51114"
SQ SEQUENCE 568 AA; 63947 MW; C6FBCD4F23B248AF CRC64;
MAELTVEVRG SNGAFYKVFI KDVHEDSLTV VFENNWQPER QVPFNEVRLP PPPDIKKEIS
EGDEVEVYSR ANDQEPCGWW LAKVRMMKGE FYVIEYAACD ATYNEIVTFE RLRPVNQNKT
VKKNTFFKCT VDVPEDLREA CANENAHKDF KKAVGACRIF YHPETTQLMI LSASEATVKR
VNILSDMHLR SIRTKLMLMS RNEEATKHLE CTKQLAAAFH EEFVVREDLM GLAIGTHGSN
IQQARKVPGV TAIELDEDTG TFRIYGESAE AVKKARGFLE FVEDFIQVPR NLVGKVIGKN
GKVIQEIVDK SGVVRVRIEG DNENKLPRED GMVPFVFVGT KESIGNVQVL LEYHIAYLKE
VEQLRMERLQ IDEQLRQIGM GFRPSSTRGP EKEKGYATDE STVSSVQGSR SYSGRGRGRR
GPNYTSGYGT NSELSNPSET ESERKDELSD WSLAGEDDRE TRHQRDSRRR PGGRGRSVSG
GRGRGGPRGG KSSISSVLKD PDSNPYSLLD NTESDQTADT DASESHHSTN RRRRSRRRRT
DEDAVLMDGM TESDTASVNE NGLGKRCD
//
