FMR1_RAT
ID FMR1_RAT Reviewed; 593 AA.
AC Q80WE1; P70568;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Fragile X messenger ribonucleoprotein 1 {ECO:0000305};
DE AltName: Full=Fragile X messenger ribonucleoprotein {ECO:0000305};
DE Short=FMRP {ECO:0000303|Ref.1};
GN Name=Fmr1 {ECO:0000312|RGD:2623};
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 [MRNA] (ISOFORM 2).
RC STRAIN=Sprague-Dawley;
RA Rackham O., Brown C.M.;
RT "Messenger RNA encoding FMRP isoform 18 from the rat hippocampus.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-587 (ISOFORM 1).
RC STRAIN=Wistar; TISSUE=Brain;
RA Huang T., Ji H., Sittler A., Shen Y., Mandel J., Wu G.;
RT "Cloning of rat FMR1 gene.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH POLYRIBOSOME.
RX PubMed=9030614; DOI=10.1523/jneurosci.17-05-01539.1997;
RA Feng Y., Gutekunst C.A., Eberhart D.E., Yi H., Warren S.T., Hersch S.M.;
RT "Fragile X mental retardation protein: nucleocytoplasmic shuttling and
RT association with somatodendritic ribosomes.";
RL J. Neurosci. 17:1539-1547(1997).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, ASSOCIATION WITH POLYRIBOSOME, AND
RP INDUCTION.
RX PubMed=9144248; DOI=10.1073/pnas.94.10.5395;
RA Weiler I.J., Irwin S.A., Klintsova A.Y., Spencer C.M., Brazelton A.D.,
RA Miyashiro K., Comery T.A., Patel B., Eberwine J., Greenough W.T.;
RT "Fragile X mental retardation protein is translated near synapses in
RT response to neurotransmitter activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:5395-5400(1997).
RN [5]
RP SUBCELLULAR LOCATION, ASSOCIATION WITH POLYRIBOSOME, AND TISSUE
RP SPECIFICITY.
RX PubMed=14613971; DOI=10.1093/hmg/ddh009;
RA Wang H., Ku L., Osterhout D.J., Li W., Ahmadian A., Liang Z., Feng Y.;
RT "Developmentally-programmed FMRP expression in oligodendrocytes: a
RT potential role of FMRP in regulating translation in oligodendroglia
RT progenitors.";
RL Hum. Mol. Genet. 13:79-89(2004).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=15028757; DOI=10.1523/jneurosci.0099-04.2004;
RA Antar L.N., Afroz R., Dictenberg J.B., Carroll R.C., Bassell G.J.;
RT "Metabotropic glutamate receptor activation regulates fragile x mental
RT retardation protein and FMR1 mRNA localization differentially in dendrites
RT and at synapses.";
RL J. Neurosci. 24:2648-2655(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=15564573; DOI=10.1523/jneurosci.2185-04.2004;
RA Gabel L.A., Won S., Kawai H., McKinney M., Tartakoff A.M., Fallon J.R.;
RT "Visual experience regulates transient expression and dendritic
RT localization of fragile X mental retardation protein.";
RL J. Neurosci. 24:10579-10583(2004).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=16098134; DOI=10.1111/j.1601-183x.2005.00128.x;
RA Antar L.N., Dictenberg J.B., Plociniak M., Afroz R., Bassell G.J.;
RT "Localization of FMRP-associated mRNA granules and requirement of
RT microtubules for activity-dependent trafficking in hippocampal neurons.";
RL Genes Brain Behav. 4:350-359(2005).
RN [9]
RP SUBCELLULAR LOCATION, ASSOCIATION WITH POLYRIBOSOME, AND ASSOCIATION WITH
RP MRNP.
RX PubMed=16571602; DOI=10.1093/hmg/ddl074;
RA Davidovic L., Bechara E., Gravel M., Jaglin X.H., Tremblay S., Sik A.,
RA Bardoni B., Khandjian E.W.;
RT "The nuclear microspherule protein 58 is a novel RNA-binding protein that
RT interacts with fragile X mental retardation protein in polyribosomal mRNPs
RT from neurons.";
RL Hum. Mol. Genet. 15:1525-1538(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-336; SER-337; SER-347;
RP SER-349 AND SER-350, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [11]
RP INTERACTION WITH KCNT1.
RX PubMed=20512134; DOI=10.1038/nn.2563;
RA Brown M.R., Kronengold J., Gazula V.R., Chen Y., Strumbos J.G.,
RA Sigworth F.J., Navaratnam D., Kaczmarek L.K.;
RT "Fragile X mental retardation protein controls gating of the sodium-
RT activated potassium channel Slack.";
RL Nat. Neurosci. 13:819-821(2010).
RN [12]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23891804; DOI=10.1016/j.mcn.2013.07.009;
RA Giampetruzzi A., Carson J.H., Barbarese E.;
RT "FMRP and myelin protein expression in oligodendrocytes.";
RL Mol. Cell. Neurosci. 56:333-341(2013).
RN [13]
RP FUNCTION, INTERACTION WITH CACNA1B, AND SUBCELLULAR LOCATION.
RX PubMed=24709664; DOI=10.1038/ncomms4628;
RA Ferron L., Nieto-Rostro M., Cassidy J.S., Dolphin A.C.;
RT "Fragile X mental retardation protein controls synaptic vesicle exocytosis
RT by modulating N-type calcium channel density.";
RL Nat. Commun. 5:3628-3628(2014).
CC -!- FUNCTION: Multifunctional polyribosome-associated RNA-binding protein
CC that plays a central role in neuronal development and synaptic
CC plasticity through the regulation of alternative mRNA splicing, mRNA
CC stability, mRNA dendritic transport and postsynaptic local protein
CC synthesis of a subset of mRNAs (PubMed:9144248). Plays a role in the
CC alternative splicing of its own mRNA (By similarity). Plays a role in
CC mRNA nuclear export (By similarity). Together with export factor NXF2,
CC is involved in the regulation of the NXF1 mRNA stability in neurons (By
CC similarity). Stabilizes the scaffolding postsynaptic density protein
CC DLG4/PSD-95 and the myelin basic protein MBP mRNAs in hippocampal
CC neurons and glial cells, respectively; this stabilization is further
CC increased in response to metabotropic glutamate receptor (mGluR)
CC stimulation (By similarity). Plays a role in selective delivery of a
CC subset of dendritic mRNAs to synaptic sites in response to mGluR
CC activation in a kinesin-dependent manner (By similarity). Plays a role
CC as a repressor of mRNA translation during the transport of dendritic
CC mRNAs to postsynaptic dendritic spines (PubMed:9144248). Component of
CC the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA
CC translation initiation (By similarity). Represses mRNA translation by
CC stalling ribosomal translocation during elongation (By similarity).
CC Reports are contradictory with regards to its ability to mediate
CC translation inhibition of (MBP) mRNA in oligodendrocytes (By
CC similarity). Also involved in the recruitment of the RNA helicase MOV10
CC to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated
CC translational repression by AGO2 (By similarity). Facilitates the
CC assembly of miRNAs on specific target mRNAs (By similarity). Also plays
CC a role as an activator of mRNA translation of a subset of dendritic
CC mRNAs at synapses (By similarity). In response to mGluR stimulation,
CC FMR1-target mRNAs are rapidly derepressed, allowing for local
CC translation at synapses (By similarity). Binds to a large subset of
CC dendritic mRNAs that encode a myriad of proteins involved in pre- and
CC postsynaptic functions (By similarity). Binds to 5'-ACU[GU]-3' and/or
CC 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at
CC coding sequence (CDS) and 3'-untranslated region (UTR) and less
CC frequently at 5'-UTR (By similarity). Binds to intramolecular G-
CC quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (By
CC similarity). Binds to G-quadruplex structures in the 3'-UTR of its own
CC mRNA (By similarity). Binds also to RNA ligands harboring a kissing
CC complex (kc) structure; this binding may mediate the association of
CC FMR1 with polyribosomes (By similarity). Binds mRNAs containing U-rich
CC target sequences (By similarity). Binds to a triple stem-loop RNA
CC structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the
CC 5'-UTR region of superoxide dismutase SOD1 mRNA (By similarity). Binds
CC to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which
CC may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1
CC target mRNAs at synapses (By similarity). Associates with export factor
CC NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-
CC dependent manner (By similarity). Binds to a subset of miRNAs in the
CC brain (By similarity). May associate with nascent transcripts in a
CC nuclear protein NXF1-dependent manner (By similarity). In vitro, binds
CC to RNA homomer; preferentially on poly(G) and to a lesser extent on
CC poly(U), but not on poly(A) or poly(C) (By similarity). Moreover, plays
CC a role in the modulation of the sodium-activated potassium channel
CC KCNT1 gating activity (By similarity). Negatively regulates the
CC voltage-dependent calcium channel current density in soma and
CC presynaptic terminals of dorsal root ganglion (DRG) neurons, and hence
CC regulates synaptic vesicle exocytosis (PubMed:24709664). Modulates the
CC voltage-dependent calcium channel CACNA1B expression at the plasma
CC membrane by targeting the channels for proteosomal degradation (By
CC similarity). Plays a role in regulation of MAP1B-dependent microtubule
CC dynamics during neuronal development (By similarity). Recently, has
CC been shown to play a translation-independent role in the modulation of
CC presynaptic action potential (AP) duration and neurotransmitter release
CC via large-conductance calcium-activated potassium (BK) channels in
CC hippocampal and cortical excitatory neurons (By similarity). Finally,
CC FMR1 may be involved in the control of DNA damage response (DDR)
CC mechanisms through the regulation of ATR-dependent signaling pathways
CC such as histone H2AX/H2A.x and BRCA1 phosphorylations (By similarity).
CC {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q06787,
CC ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:9144248}.
CC -!- SUBUNIT: Homodimer (By similarity). Forms heterodimer with FXR1;
CC heterodimerization occurs in a methylation-dependent manner (By
CC similarity). Forms heterodimer with FXR2 (By similarity). Homooligomer
CC (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex at least
CC composed of CYFIP, EIF4E and FMR1; this mRNA cap binding complex
CC formation increases in presence of the brain cytoplasmic RNA BC1 and is
CC dynamically regulated in an activity-dependent manner to repress and
CC then possibly release dendritic mRNAs for translation in response to
CC mGluR stimulation (By similarity). Associates with the SMN core complex
CC that contains SMN, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6,
CC GEMIN7, GEMIN8 and STRAP/UNRIP (By similarity). Part of a
CC ribonucleoprotein complex with AGO2/EIF2C2 and miRNAs (By similarity).
CC Interacts with AGO2/EIF2C2 (By similarity). Interacts (via C-terminus)
CC with CACNA1B; this interaction induces a decrease in the number of
CC presynaptic functional CACNA1B channels at the cell surface
CC (PubMed:24709664). Interacts with CYFIP1; this interaction recruits
CC CYFIP1 to capped mRNA. Interacts with CYFIP2 (By similarity). Interacts
CC with EIF5; this interaction occurs in a RNA-dependent manner (By
CC similarity). Interacts with dynein (By similarity). Interacts with FXR1
CC and FXR2 (By similarity). Interacts with methylated histone H3 (By
CC similarity). Interacts with IGF2BP1; this interaction allows to recruit
CC IGF2BP1 to mRNA in a FMR1-dependent manner (By similarity). Interacts
CC (via N-terminus) with KCNMB4 (By similarity). Interacts with KCNT1 (via
CC C-terminus); this interaction alters gating properties of KCNT1
CC (PubMed:20512134). Interacts (via C-terminus) with KIF5A; this
CC interaction is increased in a mGluR-dependent manner (By similarity).
CC Interacts (via phosphorylated form) with MCRS1 (via N-terminus) (By
CC similarity). Interacts with MOV10; this interaction is direct, occurs
CC in an RNA-dependent manner on polysomes and induces association of
CC MOV10 with RNAs (By similarity). Interacts with MYO5A and PURA; these
CC interactions occur in association with polyribosome (By similarity).
CC Interacts with NCL (By similarity). Interacts with NUFIP1 (By
CC similarity). Interacts (via N-terminus) with NUFIP2 (By similarity).
CC Interacts with NXF1; this interaction occurs in a mRNA-dependent and
CC polyribosome-independent manner in the nucleus (By similarity).
CC Interacts with NXF2 (via N-terminus); this interaction is direct and
CC occurs in a NXF1 mRNA-containing mRNP complexes (By similarity).
CC Interacts with RANBP9; this interaction is direct and inhibits binding
CC of FMR1 to RNA homomer (By similarity). Interacts with RPLP0 (By
CC similarity). Interacts (via C-terminus) with SMN (via C-terminus); this
CC interaction is direct and occurs in a RNA-independent manner (By
CC similarity). Interacts with TDRD3 (via C-terminus); this interaction is
CC direct (By similarity). Interacts with YBX1; this interaction occurs in
CC association with polyribosome (By similarity). Interacts with
CC nucleosome (By similarity). Associates with polyribosome; this
CC association occurs in a mRNA-dependent manner (PubMed:9030614,
CC PubMed:9144248, PubMed:14613971, PubMed:16571602). Associates with
CC messenger ribonucleoprotein particles (mRNPs) (PubMed:16571602).
CC Associates with microtubules in a kinesin- and dynein-dependent manner
CC (By similarity). Interacts with HABP4 (By similarity). Interacts with
CC SND1 (By similarity). {ECO:0000250|UniProtKB:P35922,
CC ECO:0000250|UniProtKB:Q06787, ECO:0000269|PubMed:14613971,
CC ECO:0000269|PubMed:16571602, ECO:0000269|PubMed:20512134,
CC ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:9030614,
CC ECO:0000269|PubMed:9144248}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9030614}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q06787}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:P35922}. Chromosome
CC {ECO:0000250|UniProtKB:P35922}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P35922}. Perikaryon
CC {ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:15564573, ECO:0000269|PubMed:16571602,
CC ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:9030614,
CC ECO:0000269|PubMed:9144248}. Cytoplasm, Cytoplasmic ribonucleoprotein
CC granule {ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:16098134,
CC ECO:0000269|PubMed:23891804}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q06787}. Cell projection, neuron projection
CC {ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:24709664}. Cell
CC projection, dendrite {ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:15564573, ECO:0000269|PubMed:16571602,
CC ECO:0000269|PubMed:9030614, ECO:0000269|PubMed:9144248}. Cell
CC projection, dendritic spine {ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:16098134, ECO:0000269|PubMed:9030614,
CC ECO:0000269|PubMed:9144248}. Cell projection, growth cone
CC {ECO:0000269|PubMed:16098134}. Cell projection, filopodium
CC {ECO:0000269|PubMed:16098134}. Cell projection, filopodium tip
CC {ECO:0000250|UniProtKB:P35922}. Cell projection, axon
CC {ECO:0000269|PubMed:9030614}. Synapse {ECO:0000269|PubMed:15028757}.
CC Synapse, synaptosome {ECO:0000269|PubMed:15564573,
CC ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:9030614,
CC ECO:0000269|PubMed:9144248}. Postsynaptic density
CC {ECO:0000269|PubMed:9144248}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:P35922}. Cell membrane
CC {ECO:0000250|UniProtKB:P35922}. Note=Colocalizes with H2AX/H2A.x in
CC pericentromeric heterochromatin in response to DNA damaging agents (By
CC similarity). Localizes on meiotic pachytene-stage chromosomes (By
CC similarity). Forms nuclear foci representing sites of ongoing DNA
CC replication in response to DNA damaging agents (By similarity).
CC Shuttles between nucleus and cytoplasm in a XPO1/CRM1-dependent manner
CC (By similarity). Localizes to cytoplasmic granules, also referred to as
CC messenger ribonucleoprotein particles or mRNPs, along dendrites and
CC dendritic spines (PubMed:15028757, PubMed:23891804). FMR1-containing
CC cytoplasmic granules colocalize to F-actin-rich structures, including
CC filopodium, spines and growth cone during the development of
CC hippocampal neurons (PubMed:16098134). FMR1-containing cytoplasmic
CC granules are transported out of the soma along axon and dendrite to
CC synaptic contacts in a microtubule- and kinesin-dependent manner
CC (PubMed:16098134). Colocalizes with CACNA1B in the cytoplasm and at the
CC cell membrane of neurons (By similarity). Colocalizes with CYFIP1,
CC CYFIP2, NXF2 and ribosomes in the perinuclear region (By similarity).
CC Colocalizes with CYFIP1 and EIF4E in dendrites and probably at synapses
CC (By similarity). Colocalizes with FXR1, kinesin, 60S acidic ribosomal
CC protein RPLP0 and SMN in cytoplasmic granules in the soma and neurite
CC cell processes (By similarity). Colocalizes with FXR1 and FXR2 in
CC discrete granules, called fragile X granules (FXGs), along axon and
CC presynaptic compartments (By similarity). Colocalizes with TDRD3 in
CC cytoplasmic stress granules (SGs) in response to various cellular
CC stress (By similarity). {ECO:0000250|UniProtKB:P35922,
CC ECO:0000250|UniProtKB:Q06787, ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:16098134, ECO:0000269|PubMed:23891804}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80WE1-1; Sequence=Displayed;
CC Name=2; Synonyms=18;
CC IsoId=Q80WE1-2; Sequence=VSP_034393;
CC -!- TISSUE SPECIFICITY: Expressed in brain (PubMed:9030614). Expressed in
CC neurons (PubMed:9030614). Expressed in mature oligodendrocytes (OLGs)
CC (PubMed:23891804). Expressed in oligodendroglia progenitor cells (OPCs)
CC and immature oligodendrocytes (OLGs) in the neonatal brain (at protein
CC level) (PubMed:14613971). {ECO:0000269|PubMed:14613971,
CC ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:9030614}.
CC -!- INDUCTION: Up-regulated in response to the activation of group I
CC metabotropic glutamate receptors at synapses (PubMed:9144248). Rapidly
CC and transiently up-regulated in response to light exposure in the cell
CC bodies and dendrites of visual cortical neurons (at protein level)
CC (PubMed:15564573). {ECO:0000269|PubMed:15564573,
CC ECO:0000269|PubMed:9144248}.
CC -!- DOMAIN: The N-terminal 134 amino acids are necessary for
CC homodimerization and RNA-binding. The N-terminal 298 amino acids are
CC sufficient to interact with KCNMB4 and to regulate presynaptic action
CC potential (AP) duration in neurons. The two agenet-like domains are
CC necessary for binding to histone H3 in a methylation-dependent manner.
CC The KH domains are necessary for mediating miRNA annealing to specific
CC RNA targets. The KH 2 domain is necessary for binding to kissing
CC complex (kc) RNA ligands. The RGG box domain is necessary for binding
CC to mRNA targets that contain G-quadruplex structures. The RGG-box
CC domain is necessary for binding to a triple stem-loop RNA structure,
CC called Sod1 stem loop interacting with FMRP (SoSLIP), in the superoxide
CC dismutase SOD1 mRNA. The RGG box domain is necessary for binding to its
CC own mRNA. The RGG-box domain is necessary for binding to homomer
CC poly(G). {ECO:0000250|UniProtKB:Q06787}.
CC -!- PTM: Phosphorylated on several serine residues. Phosphorylation at Ser-
CC 478 is required for phosphorylation of other nearby serine residues.
CC Phosphorylation has no effect on the binding of individual mRNA
CC species, but may affect the association with polyribosome.
CC Unphosphorylated FMR1 is associated with actively translating
CC polyribosome, whereas a fraction of phosphorylated FMR1 is associated
CC with apparently stalled polyribosome. Dephosphorylation by an activated
CC phosphatase may release the FMR1-mediated translational repression and
CC allow synthesis of a locally required protein at snypases.
CC {ECO:0000250|UniProtKB:P35922}.
CC -!- PTM: Monoubiquitinated. Polyubiquitinated. Ubiquitinated and targeted
CC for proteasomal degradation after activation of metabotropic glutamate
CC receptor (mGluR). {ECO:0000250|UniProtKB:P35922}.
CC -!- PTM: Monomethylated and asymmetrically dimethylated at four arginine
CC residues of the arginine-glycine-glycine box. Methylation disrupts the
CC binding of FMRP to RNAs through its RGG box. Methylation is necessary
CC for heterodimerization with FXR1, association with polyribosomes,
CC recruitment into stress granules and translation of FMR1 target mRNAs.
CC Methylated by PRMT1, PRMT3 and PRMT4, in vitro.
CC {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q06787}.
CC -!- SIMILARITY: Belongs to the FMR1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB07073.1; Type=Miscellaneous discrepancy; Note=N-ter sequencing errors.; Evidence={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; AY240947; AAP15341.1; -; mRNA.
DR EMBL; U60145; AAB07073.1; ALT_SEQ; mRNA.
DR RefSeq; NP_434691.1; NM_052804.1. [Q80WE1-2]
DR RefSeq; XP_006229594.1; XM_006229532.3. [Q80WE1-1]
DR AlphaFoldDB; Q80WE1; -.
DR SMR; Q80WE1; -.
DR BioGRID; 247050; 4.
DR IntAct; Q80WE1; 2.
DR MINT; Q80WE1; -.
DR STRING; 10116.ENSRNOP00000016227; -.
DR iPTMnet; Q80WE1; -.
DR PhosphoSitePlus; Q80WE1; -.
DR jPOST; Q80WE1; -.
DR PaxDb; Q80WE1; -.
DR PRIDE; Q80WE1; -.
DR Ensembl; ENSRNOT00000087893; ENSRNOP00000074033; ENSRNOG00000057464. [Q80WE1-2]
DR GeneID; 24948; -.
DR KEGG; rno:24948; -.
DR CTD; 2332; -.
DR RGD; 2623; Fmr1.
DR VEuPathDB; HostDB:ENSRNOG00000057464; -.
DR eggNOG; ENOG502QPKJ; Eukaryota.
DR GeneTree; ENSGT00950000183189; -.
DR InParanoid; Q80WE1; -.
DR PhylomeDB; Q80WE1; -.
DR PRO; PR:Q80WE1; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000057464; Expressed in thymus and 20 other tissues.
DR ExpressionAtlas; Q80WE1; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0015030; C:Cajal body; ISO:RGD.
DR GO; GO:0044297; C:cell body; IDA:MGI.
DR GO; GO:0042995; C:cell projection; ISO:RGD.
DR GO; GO:0010369; C:chromocenter; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:1902737; C:dendritic filopodium; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0044327; C:dendritic spine head; IDA:RGD.
DR GO; GO:0044326; C:dendritic spine neck; IDA:RGD.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:1990812; C:growth cone filopodium; ISS:UniProtKB.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:1990124; C:messenger ribonucleoprotein complex; ISO:RGD.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:MGI.
DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; ISO:RGD.
DR GO; GO:0099524; C:postsynaptic cytosol; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISS:UniProtKB.
DR GO; GO:0099523; C:presynaptic cytosol; ISO:RGD.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1990635; C:proximal dendrite; IDA:RGD.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0032797; C:SMN complex; ISO:RGD.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:RGD.
DR GO; GO:0097444; C:spine apparatus; IDA:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0070840; F:dynein complex binding; ISS:UniProtKB.
DR GO; GO:0002151; F:G-quadruplex RNA binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IPI:RGD.
DR GO; GO:0034046; F:poly(G) binding; ISS:UniProtKB.
DR GO; GO:0008266; F:poly(U) RNA binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:RGD.
DR GO; GO:0043022; F:ribosome binding; ISO:RGD.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:RGD.
DR GO; GO:0003723; F:RNA binding; IDA:RGD.
DR GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
DR GO; GO:0033592; F:RNA strand annealing activity; ISS:UniProtKB.
DR GO; GO:1990825; F:sequence-specific mRNA binding; ISS:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB.
DR GO; GO:0031369; F:translation initiation factor binding; ISO:RGD.
DR GO; GO:0045182; F:translation regulator activity; IDA:SynGO.
DR GO; GO:0030371; F:translation repressor activity; ISS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0008089; P:anterograde axonal transport; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0072711; P:cellular response to hydroxyurea; ISO:RGD.
DR GO; GO:1904009; P:cellular response to monosodium glutamate; IEP:RGD.
DR GO; GO:0035865; P:cellular response to potassium ion; IEP:RGD.
DR GO; GO:0034644; P:cellular response to UV; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; ISO:RGD.
DR GO; GO:0060996; P:dendritic spine development; ISO:RGD.
DR GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IEP:RGD.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0098976; P:excitatory chemical synaptic transmission; ISO:RGD.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0098977; P:inhibitory chemical synaptic transmission; ISO:RGD.
DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; ISO:RGD.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:2000766; P:negative regulation of cytoplasmic translation; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR GO; GO:1900453; P:negative regulation of long-term synaptic depression; ISS:UniProtKB.
DR GO; GO:1902373; P:negative regulation of mRNA catabolic process; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:RGD.
DR GO; GO:0010955; P:negative regulation of protein processing; IMP:RGD.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IMP:RGD.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISS:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; ISO:RGD.
DR GO; GO:1901254; P:positive regulation of intracellular transport of viral material; ISO:RGD.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; IMP:RGD.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IMP:RGD.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:1902416; P:positive regulation of mRNA binding; ISS:UniProtKB.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IMP:RGD.
DR GO; GO:0045727; P:positive regulation of translation; ISS:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0060998; P:regulation of dendritic spine development; ISS:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0060964; P:regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:1905244; P:regulation of modification of synaptic structure; ISO:RGD.
DR GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
DR GO; GO:0098908; P:regulation of neuronal action potential; IMP:RGD.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; TAS:RGD.
DR GO; GO:0099578; P:regulation of translation at postsynapse, modulating synaptic transmission; ISO:RGD.
DR GO; GO:0099577; P:regulation of translation at presynapse, modulating synaptic transmission; IDA:SynGO.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0097396; P:response to interleukin-17; ISO:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0060538; P:skeletal muscle organ development; ISS:UniProtKB.
DR GO; GO:0035176; P:social behavior; ISO:RGD.
DR GO; GO:0019226; P:transmission of nerve impulse; ISO:RGD.
DR Gene3D; 3.30.1370.10; -; 2.
DR InterPro; IPR008395; Agenet-like_dom.
DR InterPro; IPR040148; FMR1.
DR InterPro; IPR040472; FMRP_KH0.
DR InterPro; IPR032196; FXMR_C2.
DR InterPro; IPR022034; FXMRP1_C_core.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR041560; Tudor_FRX1.
DR PANTHER; PTHR10603; PTHR10603; 1.
DR Pfam; PF05641; Agenet; 1.
DR Pfam; PF16098; FXMR_C2; 2.
DR Pfam; PF12235; FXMRP1_C_core; 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; SSF54791; 2.
DR PROSITE; PS51641; AGENET_LIKE; 2.
DR PROSITE; PS50084; KH_TYPE_1; 2.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Cell membrane;
KW Cell projection; Centromere; Chromosome; Cytoplasm; DNA damage; Membrane;
KW Methylation; mRNA processing; mRNA splicing; mRNA transport; Neurogenesis;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Ribonucleoprotein; RNA-binding; RNA-mediated gene silencing; Synapse;
KW Synaptosome; Translation regulation; Transport; Ubl conjugation.
FT CHAIN 1..593
FT /note="Fragile X messenger ribonucleoprotein 1"
FT /id="PRO_0000342185"
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..348
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 1..184
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT REGION 172..211
FT /note="Necessary for interaction with CYFIP1, CYFIP2, FXR1
FT and FXR2"
FT /evidence="ECO:0000250|UniProtKB:P35922,
FT ECO:0000250|UniProtKB:Q06787"
FT REGION 323..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 375..469
FT /note="Required for nuclear export"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT REGION 397..593
FT /note="Interaction with RANBP9"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT REGION 421..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 512..526
FT /note="RNA-binding RGG-box"
FT /evidence="ECO:0000250"
FT MOTIF 402..421
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOTIF 505..512
FT /note="Nucleolar localization signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOTIF 574..578
FT /note="Nucleolar localization signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT COMPBIAS 329..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..515
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..549
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..564
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..582
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 449
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOD_RES 512
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 512
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 517
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 517
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 522
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 522
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 524
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 524
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT MOD_RES 581
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35922"
FT VAR_SEQ 469..480
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034393"
FT CONFLICT 110
FT /note="E -> D (in Ref. 2; AAB07073)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="L -> S (in Ref. 2; AAB07073)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="A -> V (in Ref. 2; AAB07073)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 593 AA; 66780 MW; 8EFBEC47E6B818F4 CRC64;
MEELVVEVRG SNGAFYKAFV KDVHEDSITV AFENNWQPER QIPFHDVRFP PPVGYNKDIN
ESDEVEVYSR ANEKEPCCWW LAKVRMIKGE FYVIEYAACD ATYNEIVTIE RLRSVNPNKP
ATKDTFHKIK LEVPEDLRQM CAKESAHKDF KKAVGAFSVT YDPENYQLVI LSINEVTSKR
AHMLIDMHFR SLRTKLSLIL RNEEASKQLE SSRQLASRFH EQFIVREDLM GLAIGTHGAN
IQQARKVPGV TAIDLDEDTC TFHIYGEDQD AVKKARSFLE FAEDVIQVPR NLVGKVIGKN
GKLIQEIVDK SGVVRVRIEA ENEKSVPQEE ENLPPSSLPS NNSRVGSNSS EEKKHLDTKE
NTHFSQPNST KVQRGMVPFV FVGTKDSIAN ATVLLDYHLN YLKEVDQLRL ERLQIDEQLR
QIGASSRPPP NRTDKEKGYV TDDGQGMGRG SRPYRNRGHG RRGPGYTSGT NSEASNASET
ESDHRDELSD WSLAPTEEER ESFLRRGDGR RRGGGGRGQG GRGRGGGFKG NDDHSRTDNR
PRNPRETKGR TTDGSLQSTS SEGSRLRTGK DRNQKKEKPD SVDGLQPLVN GVP
