FMR1_MOUSE
ID FMR1_MOUSE Reviewed; 614 AA.
AC P35922;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Fragile X messenger ribonucleoprotein 1 {ECO:0000305};
DE AltName: Full=Fragile X messenger ribonucleoprotein {ECO:0000305};
DE Short=FMRP {ECO:0000303|PubMed:10567518};
DE AltName: Full=Protein FMR-1 {ECO:0000303|PubMed:8358432};
DE Short=mFmr1p;
GN Name=Fmr1 {ECO:0000312|MGI:MGI:95564};
GN Synonyms=Fmr-1 {ECO:0000303|PubMed:8358432};
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 [MRNA], AND ALTERNATIVE SPLICING.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8358432; DOI=10.1038/ng0793-244;
RA Ashley C.T. Jr., Sutcliffe J.S., Kunst C.B., Leiner H.A., Eichler E.E.,
RA Nelson D.L., Warren S.T.;
RT "Human and murine FMR-1: alternative splicing and translational initiation
RT downstream of the CGG-repeat.";
RL Nat. Genet. 4:244-251(1993).
RN [2]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=8033209;
RA Bakker C.B., Verheij C., Willemsen R., van der Helm R., Oerlemans F.,
RA Vermey M., Bygrave A., Hoogeveen A.T., Oostra B.A.;
RT "Fmr1 knockout mice: a model to study fragile X mental retardation.";
RL Cell 78:23-33(1994).
RN [3]
RP SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, AND MUTAGENESIS OF
RP 429-LEU--LEU-431.
RX PubMed=8895584; DOI=10.1002/j.1460-2075.1996.tb00924.x;
RA Fridell R.A., Benson R.E., Hua J., Bogerd H.P., Cullen B.R.;
RT "A nuclear role for the Fragile X mental retardation protein.";
RL EMBO J. 15:5408-5414(1996).
RN [4]
RP SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, ASSOCIATION WITH
RP POLYRIBOSOME AND MRNP, AND MUTAGENESIS OF 429-LEU--LEU-434.
RX PubMed=8842725; DOI=10.1093/hmg/5.8.1083;
RA Eberhart D.E., Malter H.E., Feng Y., Warren S.T.;
RT "The fragile X mental retardation protein is a ribonucleoprotein containing
RT both nuclear localization and nuclear export signals.";
RL Hum. Mol. Genet. 5:1083-1091(1996).
RN [5]
RP SUBCELLULAR LOCATION, ASSOCIATION WITH POLYRIBOSOME, AND ASSOCIATION WITH
RP MRNP.
RX PubMed=9285783; DOI=10.1093/hmg/6.9.1465;
RA Corbin F., Bouillon M., Fortin A., Morin S., Rousseau F., Khandjian E.W.;
RT "The fragile X mental retardation protein is associated with poly(A)+ mRNA
RT in actively translating polyribosomes.";
RL Hum. Mol. Genet. 6:1465-1472(1997).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9144249; DOI=10.1073/pnas.94.10.5401;
RA Comery T.A., Harris J.B., Willems P.J., Oostra B.A., Irwin S.A.,
RA Weiler I.J., Greenough W.T.;
RT "Abnormal dendritic spines in fragile X knockout mice: maturation and
RT pruning deficits.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:5401-5404(1997).
RN [7]
RP INTERACTION WITH NUFIP1.
RX PubMed=10556305; DOI=10.1093/hmg/8.13.2557;
RA Bardoni B., Schenck A., Mandel J.-L.;
RT "A novel RNA-binding nuclear protein that interacts with the fragile X
RT mental retardation (FMR1) protein.";
RL Hum. Mol. Genet. 8:2557-2566(1999).
RN [8]
RP INTERACTION WITH FXR1; FXR2 AND NCL.
RX PubMed=10567518; DOI=10.1128/mcb.19.12.7925;
RA Ceman S., Brown V., Warren S.T.;
RT "Isolation of an FMRP-associated messenger ribonucleoprotein particle and
RT identification of nucleolin and the fragile X-related proteins as
RT components of the complex.";
RL Mol. Cell. Biol. 19:7925-7932(1999).
RN [9]
RP INTERACTION WITH YBX1.
RX PubMed=11162447; DOI=10.1006/bbrc.2000.4035;
RA Ceman S., Nelson R., Warren S.T.;
RT "Identification of mouse YB1/p50 as a component of the FMRP-associated mRNP
RT particle.";
RL Biochem. Biophys. Res. Commun. 279:904-908(2000).
RN [10]
RP ASSOCIATION WITH MRNP, AND RNA-BINDING.
RX PubMed=11719188; DOI=10.1016/s0092-8674(01)00568-2;
RA Brown V., Jin P., Ceman S., Darnell J.C., O'Donnell W.T., Tenenbaum S.A.,
RA Jin X., Feng Y., Wilkinson K.D., Keene J.D., Darnell R.B., Warren S.T.;
RT "Microarray identification of FMRP-associated brain mRNAs and altered mRNA
RT translational profiles in fragile X syndrome.";
RL Cell 107:477-487(2001).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11438589; DOI=10.1523/jneurosci.21-14-05139.2001;
RA Nimchinsky E.A., Oberlander A.M., Svoboda K.;
RT "Abnormal development of dendritic spines in FMR1 knock-out mice.";
RL J. Neurosci. 21:5139-5146(2001).
RN [12]
RP FUNCTION, INTERACTION WITH FXR2, AND RNA-BINDING.
RX PubMed=11376146; DOI=10.1093/nar/29.11.2276;
RA Li Z., Zhang Y., Ku L., Wilkinson K.D., Warren S.T., Feng Y.;
RT "The fragile X mental retardation protein inhibits translation via
RT interacting with mRNA.";
RL Nucleic Acids Res. 29:2276-2283(2001).
RN [13]
RP INTERACTION WITH CYFIP1 AND CYFIP2, AND SUBCELLULAR LOCATION.
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 [14]
RP INTERACTION WITH MYO5A AND PURA.
RX PubMed=12147688; DOI=10.1074/jbc.m203608200;
RA Ohashi S., Koike K., Omori A., Ichinose S., Ohara S., Kobayashi S.,
RA Sato T.A., Anzai K.;
RT "Identification of mRNA/protein (mRNP) complexes containing Puralpha,
RT mStaufen, fragile X protein, and myosin Va and their association with rough
RT endoplasmic reticulum equipped with a kinesin motor.";
RL J. Biol. Chem. 277:37804-37810(2002).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12032354; DOI=10.1073/pnas.122205699;
RA Huber K.M., Gallagher S.M., Warren S.T., Bear M.F.;
RT "Altered synaptic plasticity in a mouse model of fragile X mental
RT retardation.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7746-7750(2002).
RN [16]
RP FUNCTION, ASSOCIATION WITH POLYRIBOSOME AND MRNP, RNA-BINDING, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12581522; DOI=10.1016/s0092-8674(03)00079-5;
RA Zalfa F., Giorgi M., Primerano B., Moro A., Di Penta A., Reis S.,
RA Oostra B., Bagni C.;
RT "The fragile X syndrome protein FMRP associates with BC1 RNA and regulates
RT the translation of specific mRNAs at synapses.";
RL Cell 112:317-327(2003).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-499, MUTAGENESIS OF
RP SER-499, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14570712; DOI=10.1093/hmg/ddg350;
RA Ceman S., O'Donnell W.T., Reed M., Patton S., Pohl J., Warren S.T.;
RT "Phosphorylation influences the translation state of FMRP-associated
RT polyribosomes.";
RL Hum. Mol. Genet. 12:3295-3305(2003).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, ASSOCIATION WITH POLYRIBOSOME, AND
RP ASSOCIATION WITH MRNP.
RX PubMed=12575950; DOI=10.1016/s0896-6273(03)00034-5;
RA Miyashiro K.Y., Beckel-Mitchener A., Purk T.P., Becker K.G., Barret T.,
RA Liu L., Carbonetto S., Weiler I.J., Greenough W.T., Eberwine J.;
RT "RNA cargoes associating with FMRP reveal deficits in cellular functioning
RT in Fmr1 null mice.";
RL Neuron 37:417-431(2003).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12927206; DOI=10.1016/s0306-4522(03)00406-8;
RA Chen L., Yun S.W., Seto J., Liu W., Toth M.;
RT "The fragile X mental retardation protein binds and regulates a novel class
RT of mRNAs containing U rich target sequences.";
RL Neuroscience 120:1005-1017(2003).
RN [20]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=14614133; DOI=10.1073/pnas.2336265100;
RA Todd P.K., Mack K.J., Malter J.S.;
RT "The fragile X mental retardation protein is required for type-I
RT metabotropic glutamate receptor-dependent translation of PSD-95.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14374-14378(2003).
RN [21]
RP FUNCTION, ASSOCIATION WITH POLYRIBOSOME, RNA-BINDING, SUBCELLULAR LOCATION,
RP AND TISSUE 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 [22]
RP INTERACTION WITH RANBP9.
RX PubMed=15381419; DOI=10.1016/j.jmb.2004.08.024;
RA Menon R.P., Gibson T.J., Pastore A.;
RT "The C-terminus of fragile X mental retardation protein interacts with the
RT multi-domain Ran-binding protein in the microtubule-organising centre.";
RL J. Mol. Biol. 343:43-53(2004).
RN [23]
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 [24]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH POLYRIBOSOME.
RX PubMed=15317853; DOI=10.1523/jneurosci.2306-04.2004;
RA Stefani G., Fraser C.E., Darnell J.C., Darnell R.B.;
RT "Fragile X mental retardation protein is associated with translating
RT polyribosomes in neuronal cells.";
RL J. Neurosci. 24:7272-7276(2004).
RN [25]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15312650; DOI=10.1016/j.neuron.2004.07.022;
RA Kanai Y., Dohmae N., Hirokawa N.;
RT "Kinesin transports RNA: isolation and characterization of an RNA-
RT transporting granule.";
RL Neuron 43:513-525(2004).
RN [26]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH MRNP.
RX PubMed=15329415; DOI=10.1073/pnas.0405398101;
RA Khandjian E.W., Huot M.E., Tremblay S., Davidovic L., Mazroui R.,
RA Bardoni B.;
RT "Biochemical evidence for the association of fragile X mental retardation
RT protein with brain polyribosomal ribonucleoparticles.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13357-13362(2004).
RN [27]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15475576; DOI=10.1073/pnas.0404995101;
RA Lu R., Wang H., Liang Z., Ku L., O'donnell W.T., Li W., Warren S.T.,
RA Feng Y.;
RT "The fragile X protein controls microtubule-associated protein 1B
RT translation and microtubule stability in brain neuron development.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15201-15206(2004).
RN [28]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15548614; DOI=10.1073/pnas.0407533101;
RA Weiler I.J., Spangler C.C., Klintsova A.Y., Grossman A.W., Kim S.H.,
RA Bertaina-Anglade V., Khaliq H., de Vries F.E., Lambers F.A., Hatia F.,
RA Base C.K., Greenough W.T.;
RT "Fragile X mental retardation protein is necessary for neurotransmitter-
RT activated protein translation at synapses.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17504-17509(2004).
RN [29]
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 [30]
RP ASSOCIATION WITH POLYRIBOSOME.
RX PubMed=15805463; DOI=10.1101/gad.1276805;
RA Darnell J.C., Fraser C.E., Mostovetsky O., Stefani G., Jones T.A.,
RA Eddy S.R., Darnell R.B.;
RT "Kissing complex RNAs mediate interaction between the Fragile-X mental
RT retardation protein KH2 domain and brain polyribosomes.";
RL Genes Dev. 19:903-918(2005).
RN [31]
RP TISSUE SPECIFICITY.
RX PubMed=16000371; DOI=10.1091/mbc.e05-04-0304;
RA Huot M.-E., Bisson N., Davidovic L., Mazroui R., Labelle Y., Moss T.,
RA Khandjian E.W.;
RT "The RNA-binding protein Fragile X-related 1 regulates somite formation in
RT Xenopus laevis.";
RL Mol. Biol. Cell 16:4350-4361(2005).
RN [32]
RP METHYLATION AT ARG-533; ARG-538; ARG-543 AND ARG-545.
RX PubMed=16319129; DOI=10.1093/hmg/ddi429;
RA Stetler A., Winograd C., Sayegh J., Cheever A., Patton E., Zhang X.,
RA Clarke S., Ceman S.;
RT "Identification and characterization of the methyl arginines in the fragile
RT X mental retardation protein Fmrp.";
RL Hum. Mol. Genet. 15:87-96(2006).
RN [33]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16631377; DOI=10.1016/j.mcn.2006.02.001;
RA Antar L.N., Li C., Zhang H., Carroll R.C., Bassell G.J.;
RT "Local functions for FMRP in axon growth cone motility and activity-
RT dependent regulation of filopodia and spine synapses.";
RL Mol. Cell. Neurosci. 32:37-48(2006).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC DEGRADATION, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16908410; DOI=10.1016/j.neuron.2006.07.005;
RA Hou L., Antion M.D., Hu D., Spencer C.M., Paylor R., Klann E.;
RT "Dynamic translational and proteasomal regulation of fragile X mental
RT retardation protein controls mGluR-dependent long-term depression.";
RL Neuron 51:441-454(2006).
RN [35]
RP FUNCTION, INTERACTION WITH NXF2, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16790844; DOI=10.1261/rna.94306;
RA Lai D., Sakkas D., Huang Y.;
RT "The fragile X mental retardation protein interacts with a distinct mRNA
RT nuclear export factor NXF2.";
RL RNA 12:1446-1449(2006).
RN [36]
RP FUNCTION, ASSOCIATION WITH MRNA, AND DISRUPTION PHENOTYPE.
RX PubMed=17507556; DOI=10.1523/jneurosci.0937-07.2007;
RA Muddashetty R.S., Kelic S., Gross C., Xu M., Bassell G.J.;
RT "Dysregulated metabotropic glutamate receptor-dependent translation of AMPA
RT receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of
RT fragile X syndrome.";
RL J. Neurosci. 27:5338-5348(2007).
RN [37]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17417632; DOI=10.1038/nn1893;
RA Zalfa F., Eleuteri B., Dickson K.S., Mercaldo V., De Rubeis S.,
RA di Penta A., Tabolacci E., Chiurazzi P., Neri G., Grant S.G., Bagni C.;
RT "A new function for the fragile X mental retardation protein in regulation
RT of PSD-95 mRNA stability.";
RL Nat. Neurosci. 10:578-587(2007).
RN [38]
RP FUNCTION, INTERACTION WITH NXF2, AND TISSUE SPECIFICITY.
RX PubMed=17548835; DOI=10.1073/pnas.0700169104;
RA Zhang M., Wang Q., Huang Y.;
RT "Fragile X mental retardation protein FMRP and the RNA export factor NXF2
RT associate with and destabilize Nxf1 mRNA in neuronal cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10057-10062(2007).
RN [39]
RP FUNCTION, INTERACTION WITH CYFIP1-EIF4E COMPLEX, ASSOCIATION WITH MRNP,
RP RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=18805096; DOI=10.1016/j.cell.2008.07.031;
RA Napoli I., Mercaldo V., Boyl P.P., Eleuteri B., Zalfa F., De Rubeis S.,
RA Di Marino D., Mohr E., Massimi M., Falconi M., Witke W., Costa-Mattioli M.,
RA Sonenberg N., Achsel T., Bagni C.;
RT "The fragile X syndrome protein represses activity-dependent translation
RT through CYFIP1, a new 4E-BP.";
RL Cell 134:1042-1054(2008).
RN [40]
RP FUNCTION, INTERACTION WITH KIF5A, INTERACTION WITH DYNEIN, ASSOCIATION WITH
RP MICROTUBULES, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=18539120; DOI=10.1016/j.devcel.2008.04.003;
RA Dictenberg J.B., Swanger S.A., Antar L.N., Singer R.H., Bassell G.J.;
RT "A direct role for FMRP in activity-dependent dendritic mRNA transport
RT links filopodial-spine morphogenesis to fragile X syndrome.";
RL Dev. Cell 14:926-939(2008).
RN [41]
RP ASSOCIATION WITH THE SMN CORE COMPLEX.
RX PubMed=18093976; DOI=10.1074/jbc.m707304200;
RA Piazzon N., Rage F., Schlotter F., Moine H., Branlant C., Massenet S.;
RT "In vitro and in cellulo evidences for association of the survival of motor
RT neuron complex with the fragile X mental retardation protein.";
RL J. Biol. Chem. 283:5598-5610(2008).
RN [42]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18653529; DOI=10.1093/nar/gkn472;
RA Didiot M.C., Tian Z., Schaeffer C., Subramanian M., Mandel J.L., Moine H.;
RT "The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic
RT splicing enhancer.";
RL Nucleic Acids Res. 36:4902-4912(2008).
RN [43]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19640847; DOI=10.1074/jbc.m109.042663;
RA Schuett J., Falley K., Richter D., Kreienkamp H.J., Kindler S.;
RT "Fragile X mental retardation protein regulates the levels of scaffold
RT proteins and glutamate receptors in postsynaptic densities.";
RL J. Biol. Chem. 284:25479-25487(2009).
RN [44]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19193898; DOI=10.1523/jneurosci.3937-08.2009;
RA Christie S.B., Akins M.R., Schwob J.E., Fallon J.R.;
RT "The FXG: a presynaptic fragile X granule expressed in a subset of
RT developing brain circuits.";
RL J. Neurosci. 29:1514-1524(2009).
RN [45]
RP FUNCTION, RNA-BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=19166269; DOI=10.1371/journal.pbio.1000016;
RA Bechara E.G., Didiot M.C., Melko M., Davidovic L., Bensaid M., Martin P.,
RA Castets M., Pognonec P., Khandjian E.W., Moine H., Bardoni B.;
RT "A novel function for fragile X mental retardation protein in translational
RT activation.";
RL PLoS Biol. 7:E16-E16(2009).
RN [46]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-462 AND SER-602, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Spleen, and 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 [47]
RP FUNCTION, AND 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 [48]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=20159450; DOI=10.1016/j.neuron.2010.01.005;
RA Edbauer D., Neilson J.R., Foster K.A., Wang C.F., Seeburg D.P.,
RA Batterton M.N., Tada T., Dolan B.M., Sharp P.A., Sheng M.;
RT "Regulation of synaptic structure and function by FMRP-associated microRNAs
RT miR-125b and miR-132.";
RL Neuron 65:373-384(2010).
RN [49]
RP FUNCTION, INTERACTION WITH RPLP0, RNA-BINDING, ASSOCIATION WITH
RP POLYRIBOSOME, AND DISRUPTION PHENOTYPE.
RX PubMed=21784246; DOI=10.1016/j.cell.2011.06.013;
RA Darnell J.C., Van Driesche S.J., Zhang C., Hung K.Y., Mele A., Fraser C.E.,
RA Stone E.F., Chen C., Fak J.J., Chi S.W., Licatalosi D.D., Richter J.D.,
RA Darnell R.B.;
RT "FMRP stalls ribosomal translocation on mRNAs linked to synaptic function
RT and autism.";
RL Cell 146:247-261(2011).
RN [50]
RP FUNCTION, RNA-BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=21490210; DOI=10.1523/jneurosci.6661-10.2011;
RA Gross C., Yao X., Pong D.L., Jeromin A., Bassell G.J.;
RT "Fragile X mental retardation protein regulates protein expression and mRNA
RT translation of the potassium channel Kv4.2.";
RL J. Neurosci. 31:5693-5698(2011).
RN [51]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23235829; DOI=10.1038/nature11737;
RA Ascano M. Jr., Mukherjee N., Bandaru P., Miller J.B., Nusbaum J.D.,
RA Corcoran D.L., Langlois C., Munschauer M., Dewell S., Hafner M.,
RA Williams Z., Ohler U., Tuschl T.;
RT "FMRP targets distinct mRNA sequence elements to regulate protein
RT expression.";
RL Nature 492:382-386(2012).
RN [52]
RP LACK OF FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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 [53]
RP DISRUPTION PHENOTYPE, AND RNA-BINDING.
RX PubMed=24349419; DOI=10.1371/journal.pone.0083007;
RA Derlig K., Giessl A., Brandstatter J.H., Enz R., Dahlhaus R.;
RT "Identification and characterisation of Simiate, a novel protein linked to
RT the fragile X syndrome.";
RL PLoS ONE 8:E83007-E83007(2013).
RN [54]
RP FUNCTION, CHROMATIN BINDING, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24813610; DOI=10.1016/j.cell.2014.03.040;
RA Alpatov R., Lesch B.J., Nakamoto-Kinoshita M., Blanco A., Chen S.,
RA Stuetzer A., Armache K.J., Simon M.D., Xu C., Ali M., Murn J., Prisic S.,
RA Kutateladze T.G., Vakoc C.R., Min J., Kingston R.E., Fischle W.,
RA Warren S.T., Page D.C., Shi Y.;
RT "A chromatin-dependent role of the fragile X mental retardation protein
RT FMRP in the DNA damage response.";
RL Cell 157:869-881(2014).
RN [55]
RP INTERACTION WITH MOV10.
RX PubMed=25464849; DOI=10.1016/j.celrep.2014.10.054;
RA Kenny P.J., Zhou H., Kim M., Skariah G., Khetani R.S., Drnevich J.,
RA Arcila M.L., Kosik K.S., Ceman S.;
RT "MOV10 and FMRP regulate AGO2 association with microRNA recognition
RT elements.";
RL Cell Rep. 9:1729-1741(2014).
RN [56]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-470, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and 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 [57]
RP FUNCTION, INTERACTION WITH CACNA1B, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
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).
RN [58]
RP RNA-BINDING.
RX PubMed=25692235; DOI=10.1080/15476286.2014.996464;
RA Zhang Y., Gaetano C.M., Williams K.R., Bassell G.J., Mihailescu M.R.;
RT "FMRP interacts with G-quadruplex structures in the 3'-UTR of its dendritic
RT target Shank1 mRNA.";
RL RNA Biol. 11:1364-1374(2014).
RN [59]
RP FUNCTION, INTERACTION WITH KCNMB4, AND DISRUPTION PHENOTYPE.
RX PubMed=25561520; DOI=10.1073/pnas.1423094112;
RA Myrick L.K., Deng P.Y., Hashimoto H., Oh Y.M., Cho Y., Poidevin M.J.,
RA Suhl J.A., Visootsak J., Cavalli V., Jin P., Cheng X., Warren S.T.,
RA Klyachko V.A.;
RT "Independent role for presynaptic FMRP revealed by an FMR1 missense
RT mutation associated with intellectual disability and seizures.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:949-956(2015).
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:11438589, PubMed:12032354,
CC PubMed:15475576, PubMed:16631377, PubMed:16790844, PubMed:17417632,
CC PubMed:17548835, PubMed:18539120, PubMed:18653529, PubMed:19640847,
CC PubMed:19166269, PubMed:20159450, PubMed:21784246, PubMed:23235829,
CC PubMed:24813610). Plays a role in the alternative splicing of its own
CC mRNA (PubMed:18653529). Plays a role in mRNA nuclear export
CC (PubMed:16790844). Together with export factor NXF2, is involved in the
CC regulation of the NXF1 mRNA stability in neurons (PubMed:17548835).
CC Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and
CC the myelin basic protein MBP mRNAs in hippocampal neurons and glial
CC cells, respectively; this stabilization is further increased in
CC response to metabotropic glutamate receptor (mGluR) stimulation
CC (PubMed:17417632). Plays a role in selective delivery of a subset of
CC dendritic mRNAs to synaptic sites in response to mGluR activation in a
CC kinesin-dependent manner (PubMed:18539120). Plays a role as a repressor
CC of mRNA translation during the transport of dendritic mRNAs to
CC postsynaptic dendritic spines (PubMed:11376146, PubMed:12581522,
CC PubMed:14570712, PubMed:12927206, PubMed:15475576, PubMed:16908410,
CC PubMed:18805096, PubMed:19640847, PubMed:21784246, PubMed:23235829).
CC Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent
CC mRNA translation initiation (PubMed:18805096). Represses mRNA
CC translation by stalling ribosomal translocation during elongation
CC (PubMed:21784246). Reports are contradictory with regards to its
CC ability to mediate translation inhibition of (MBP) mRNA in
CC oligodendrocytes (PubMed:14613971, PubMed:23891804). Also involved in
CC the recruitment of the RNA helicase MOV10 to a subset of mRNAs and
CC hence regulates microRNA (miRNA)-mediated translational repression by
CC AGO2 (PubMed:20159450, PubMed:25464849). Facilitates the assembly of
CC miRNAs on specific target mRNAs (By similarity). Also plays a role as
CC an activator of mRNA translation of a subset of dendritic mRNAs at
CC synapses (PubMed:14614133, PubMed:14613971, PubMed:15548614,
CC PubMed:19640847, PubMed:19166269, PubMed:21490210). In response to
CC mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing
CC for local translation at synapses (PubMed:16908410, PubMed:17507556,
CC PubMed:19640847). Binds to a large subset of dendritic mRNAs that
CC encode a myriad of proteins involved in pre- and postsynaptic functions
CC (PubMed:11719188, PubMed:11376146, PubMed:14613971, PubMed:17507556,
CC PubMed:21784246, PubMed:21490210, PubMed:24349419). Binds to 5'-
CC ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA
CC targets, mainly at coding sequence (CDS) and 3'-untranslated region
CC (UTR) and less frequently at 5'-UTR (By similarity). Binds to
CC intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA
CC targets (PubMed:25692235). Binds to G-quadruplex structures in the 3'-
CC UTR of its own mRNA (By similarity). Binds also to RNA ligands
CC harboring a kissing complex (kc) structure; this binding may mediate
CC the association of FMR1 with polyribosomes (By similarity). Binds mRNAs
CC containing U-rich target sequences (By similarity). Binds to a triple
CC stem-loop RNA structure, called Sod1 stem loop interacting with FMRP
CC (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA
CC (PubMed:19166269). Binds to the dendritic, small non-coding brain
CC cytoplasmic RNA 1 (BC1); which may increase the association of the
CC CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses
CC (PubMed:12581522, PubMed:18805096). Associates with export factor NXF1
CC mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent
CC manner (PubMed:17548835). Binds to a subset of miRNAs in the brain
CC (PubMed:20159450). May associate with nascent transcripts in a nuclear
CC protein NXF1-dependent manner (By similarity). In vitro, binds to RNA
CC homomer; preferentially on poly(G) and to a lesser extent on poly(U),
CC but not on poly(A) or poly(C) (By similarity). Moreover, plays a role
CC in the modulation of the sodium-activated potassium channel KCNT1
CC gating activity (PubMed:20512134). Negatively regulates the voltage-
CC dependent calcium channel current density in soma and presynaptic
CC terminals of dorsal root ganglion (DRG) neurons, and hence regulates
CC synaptic vesicle exocytosis (By similarity). Modulates the voltage-
CC dependent calcium channel CACNA1B expression at the plasma membrane by
CC targeting the channels for proteosomal degradation (PubMed:24709664).
CC Plays a role in regulation of MAP1B-dependent microtubule dynamics
CC during neuronal development (PubMed:15475576). Recently, has been shown
CC to play a translation-independent role in the modulation of presynaptic
CC action potential (AP) duration and neurotransmitter release via large-
CC conductance calcium-activated potassium (BK) channels in hippocampal
CC and cortical excitatory neurons (PubMed:25561520). Finally, FMR1 may be
CC involved in the control of DNA damage response (DDR) mechanisms through
CC the regulation of ATR-dependent signaling pathways such as histone
CC H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610).
CC {ECO:0000250|UniProtKB:Q06787, ECO:0000250|UniProtKB:Q80WE1,
CC ECO:0000269|PubMed:11376146, ECO:0000269|PubMed:11438589,
CC ECO:0000269|PubMed:11719188, ECO:0000269|PubMed:12032354,
CC ECO:0000269|PubMed:12581522, ECO:0000269|PubMed:12927206,
CC ECO:0000269|PubMed:14570712, ECO:0000269|PubMed:14613971,
CC ECO:0000269|PubMed:14614133, ECO:0000269|PubMed:15475576,
CC ECO:0000269|PubMed:15548614, ECO:0000269|PubMed:16631377,
CC ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:16908410,
CC ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:17507556,
CC ECO:0000269|PubMed:17548835, ECO:0000269|PubMed:18539120,
CC ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18805096,
CC ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:19640847,
CC ECO:0000269|PubMed:20159450, ECO:0000269|PubMed:20512134,
CC ECO:0000269|PubMed:21490210, ECO:0000269|PubMed:21784246,
CC ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804,
CC ECO:0000269|PubMed:24349419, ECO:0000269|PubMed:24709664,
CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520,
CC ECO:0000269|PubMed:25692235}.
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 (PubMed:18805096). Associates with the SMN core
CC complex that contains SMN, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5,
CC GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:18093976). 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 (PubMed:11438699, PubMed:18805096). Interacts
CC with CYFIP2 (PubMed:11438699). Interacts with EIF5; this interaction
CC occurs in a RNA-dependent manner (By similarity). Interacts with dynein
CC (PubMed:18539120). Interacts with FXR1 and FXR2 (PubMed:10567518).
CC Interacts with methylated histone H3 (By similarity). Interacts with
CC IGF2BP1; this interaction allows to recruit IGF2BP1 to mRNA in a FMR1-
CC dependent manner (By similarity). Interacts (via N-terminus) with
CC KCNMB4 (PubMed:25561520). Interacts with KCNT1 (via C-terminus); this
CC interaction alters gating properties of KCNT1 (PubMed:20512134).
CC Interacts (via C-terminus) with KIF5A; this interaction is increased in
CC a mGluR-dependent manner (PubMed:18539120). Interacts (via
CC phosphorylated form) with MCRS1 (via N-terminus) (By similarity).
CC Interacts with MOV10; this interaction is direct, occurs in an RNA-
CC dependent manner on polysomes and induces association of MOV10 with
CC RNAs (PubMed:25464849). Interacts with MYO5A and PURA; these
CC interactions occur in association with polyribosome (PubMed:12147688).
CC Interacts with NCL (PubMed:10567518). Interacts with NUFIP1
CC (PubMed:10556305). Interacts (via N-terminus) with NUFIP2 (By
CC similarity). Interacts with NXF1; this interaction occurs in a mRNA-
CC dependent and polyribosome-independent manner in the nucleus (By
CC similarity). Interacts with NXF2 (via N-terminus); this interaction is
CC direct and occurs in a NXF1 mRNA-containing mRNP complexes
CC (PubMed:16790844, PubMed:17548835). Interacts with RANBP9; this
CC interaction is direct and inhibits binding of FMR1 to RNA homomer
CC (PubMed:15381419). Interacts with RPLP0 (PubMed:21784246). Interacts
CC (via C-terminus) with SMN (via C-terminus); this interaction is direct
CC and occurs in a RNA-independent manner (By similarity). Interacts with
CC TDRD3 (via C-terminus); this interaction is direct (By similarity).
CC Interacts with YBX1; this interaction occurs in association with
CC polyribosome (PubMed:11162447). Interacts with nucleosome (By
CC similarity). Associates with polyribosome; this association occurs in a
CC mRNA-dependent manner (PubMed:8842725, PubMed:9285783, PubMed:12581522,
CC PubMed:12575950, PubMed:14613971, PubMed:15317853, PubMed:15805463,
CC PubMed:21784246). Associates with messenger ribonucleoprotein particles
CC (mRNPs) (PubMed:8842725, PubMed:9285783, PubMed:11719188,
CC PubMed:12581522, PubMed:12575950, PubMed:15329415, PubMed:18805096).
CC Associates with microtubules in a kinesin- and dynein-dependent manner
CC (PubMed:18539120). Interacts with HABP4 (By similarity).
CC {ECO:0000250|UniProtKB:Q06787, ECO:0000269|PubMed:10556305,
CC ECO:0000269|PubMed:10567518, ECO:0000269|PubMed:11162447,
CC ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:11719188,
CC ECO:0000269|PubMed:12147688, ECO:0000269|PubMed:12575950,
CC ECO:0000269|PubMed:12581522, ECO:0000269|PubMed:14613971,
CC ECO:0000269|PubMed:15317853, ECO:0000269|PubMed:15329415,
CC ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15805463,
CC ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:17548835,
CC ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:18539120,
CC ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:20512134,
CC ECO:0000269|PubMed:21784246, ECO:0000269|PubMed:24709664,
CC ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:25561520,
CC ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:9285783}.
CC -!- INTERACTION:
CC P35922; Q9JHG6: Rcan1; NbExp=3; IntAct=EBI-645094, EBI-644061;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16908410,
CC ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:8895584}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q06787}. Chromosome, centromere
CC {ECO:0000269|PubMed:24813610}. Chromosome
CC {ECO:0000269|PubMed:24813610}. Cytoplasm {ECO:0000269|PubMed:11438699,
CC ECO:0000269|PubMed:14570712, ECO:0000269|PubMed:15317853,
CC ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:24709664,
CC ECO:0000269|PubMed:8895584}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:16790844,
CC ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:9285783}. Cytoplasm,
CC Cytoplasmic ribonucleoprotein granule {ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:15312650, ECO:0000269|PubMed:15329415,
CC ECO:0000269|PubMed:16098134, ECO:0000269|PubMed:18539120,
CC ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:9285783}. Cytoplasm,
CC Stress granule {ECO:0000250|UniProtKB:Q06787}. Perikaryon
CC {ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:16908410,
CC ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19193898}. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:Q06787}. Cell
CC projection, axon {ECO:0000269|PubMed:16631377,
CC ECO:0000269|PubMed:19193898}. Cell projection, dendrite
CC {ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:16631377,
CC ECO:0000269|PubMed:16908410, ECO:0000269|PubMed:18539120,
CC ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19193898}. Cell
CC projection, dendritic spine {ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:16631377}. Synapse, synaptosome
CC {ECO:0000269|PubMed:18805096}. Cell projection, filopodium
CC {ECO:0000269|PubMed:16631377}. Cell projection, growth cone
CC {ECO:0000269|PubMed:16631377}. Cell projection, filopodium tip
CC {ECO:0000269|PubMed:16631377}. Synapse {ECO:0000269|PubMed:16631377}.
CC Postsynaptic cell membrane {ECO:0000269|PubMed:19193898}. Presynaptic
CC cell membrane {ECO:0000269|PubMed:19193898}. Cell membrane
CC {ECO:0000269|PubMed:24709664}. Note=Colocalizes with H2AX/H2A.x in
CC pericentromeric heterochromatin in response to DNA damaging agents
CC (PubMed:24813610). Localizes on meiotic pachytene-stage chromosomes
CC (PubMed:24813610). Forms nuclear foci representing sites of ongoing DNA
CC replication in response to DNA damaging agents (PubMed:24813610).
CC Shuttles between nucleus and cytoplasm in a XPO1/CRM1-dependent manner
CC (PubMed:8895584, PubMed:8842725). Localizes to cytoplasmic granules,
CC also referred to as messenger ribonucleoprotein particles or mRNPs,
CC along dendrites and dendritic spines (PubMed:15028757,
CC PubMed:16631377). FMR1-containing cytoplasmic granules colocalize to F-
CC actin-rich structures, including filopodium, spines and growth cone
CC during the development of hippocampal neurons (By similarity). FMR1-
CC containing cytoplasmic granules are transported out of the soma along
CC axon and dendrite to synaptic contacts in a microtubule- and kinesin-
CC dependent manner (PubMed:15312650, PubMed:16098134, PubMed:18539120).
CC Colocalizes with CACNA1B in the cytoplasm and at the cell membrane of
CC neurons (PubMed:24709664). Colocalizes with CYFIP1, CYFIP2, NXF2 and
CC ribosomes in the perinuclear region (PubMed:11438699, PubMed:16790844).
CC Colocalizes with CYFIP1 and EIF4E in dendrites and probably at synapses
CC (PubMed:18805096). 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 (PubMed:19193898). Colocalizes with TDRD3 in
CC cytoplasmic stress granules (SGs) in response to various cellular
CC stress (By similarity). Interacts with SND1 (By similarity).
CC {ECO:0000250|UniProtKB:Q06787, ECO:0000250|UniProtKB:Q80WE1,
CC ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:15028757,
CC ECO:0000269|PubMed:15312650, ECO:0000269|PubMed:16098134,
CC ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:16790844,
CC ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:18805096,
CC ECO:0000269|PubMed:19193898, ECO:0000269|PubMed:24709664,
CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:8842725,
CC ECO:0000269|PubMed:8895584}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus
CC {ECO:0000269|PubMed:8842725}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:8842725}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=12;
CC Name=1; Synonyms=ISO1;
CC IsoId=P35922-1; Sequence=Displayed;
CC Name=2; Synonyms=ISO2;
CC IsoId=P35922-2; Sequence=VSP_002828;
CC Name=3; Synonyms=ISO3;
CC IsoId=P35922-3; Sequence=VSP_002829;
CC Name=4; Synonyms=ISO4;
CC IsoId=P35922-4; Sequence=VSP_002831, VSP_002830;
CC Name=5; Synonyms=ISO5;
CC IsoId=P35922-5; Sequence=VSP_002832, VSP_002833;
CC Name=6; Synonyms=ISO6;
CC IsoId=P35922-6; Sequence=VSP_002834, VSP_002835;
CC Name=7; Synonyms=ISO7;
CC IsoId=P35922-7; Sequence=VSP_002827;
CC Name=8; Synonyms=ISO8;
CC IsoId=P35922-8; Sequence=VSP_002827, VSP_002828;
CC Name=9; Synonyms=ISO9;
CC IsoId=P35922-9; Sequence=VSP_002827, VSP_002829;
CC Name=10; Synonyms=ISO10;
CC IsoId=P35922-10; Sequence=VSP_002827, VSP_002831, VSP_002830;
CC Name=11; Synonyms=ISO11;
CC IsoId=P35922-11; Sequence=VSP_002827, VSP_002832, VSP_002833;
CC Name=12; Synonyms=ISO12;
CC IsoId=P35922-12; Sequence=VSP_002827, VSP_002834, VSP_002835;
CC -!- TISSUE SPECIFICITY: Expressed in brain (PubMed:8033209). Strongly
CC expressed in the neonatal hippocampus (PubMed:15475576). Expressed in
CC the brainstem (PubMed:14613971). Expressed in the cerebellum
CC (PubMed:19193898). Expressed in neurons of hippocampal area CA3
CC (PubMed:17548835, PubMed:19193898). Expressed in neurons of the
CC olfactory bulb including the granule, mitral, tufted and
CC juxtaglomerular cells (PubMed:19193898). Expressed in both mature and
CC immature olfactory sensory neurons (OSNs) (PubMed:19193898). Expressed
CC in neurons in all layers and in all regions of cerebral cortex
CC (PubMed:19193898). Expressed in mature oligodendrocytes (OLGs)
CC (PubMed:23891804). Expressed in spermatogonia (at protein level)
CC (PubMed:16790844). Expressed predominantly in the brain
CC (PubMed:16000371). Expressed in testis (PubMed:8033209).
CC {ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:15475576,
CC ECO:0000269|PubMed:16000371, ECO:0000269|PubMed:16790844,
CC ECO:0000269|PubMed:17548835, ECO:0000269|PubMed:19193898,
CC ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:8033209}.
CC -!- INDUCTION: Rapidly and transiently up-regulated in response to
CC metabotropic glutamate receptor activation in a protein synthesis-
CC dependent manner in neurons (at protein level).
CC {ECO:0000269|PubMed:14614133, ECO:0000269|PubMed:16908410}.
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 (PubMed:14570712).
CC Phosphorylation at Ser-499 is required for phosphorylation of other
CC nearby serine residues (PubMed:14570712). Phosphorylation has no effect
CC on the binding of individual mRNA species, but may affect the
CC association with polyribosome (PubMed:14570712). Unphosphorylated FMR1
CC is associated with actively translating polyribosome, whereas a
CC fraction of phosphorylated FMR1 is associated with apparently stalled
CC polyribosome (PubMed:14570712). 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 (PubMed:14570712). {ECO:0000269|PubMed:14570712}.
CC -!- PTM: Monoubiquitinated (PubMed:16908410). Polyubiquitinated
CC (PubMed:16908410). Ubiquitinated and targeted for proteasomal
CC degradation after activation of metabotropic glutamate receptor (mGluR)
CC (PubMed:16908410). {ECO:0000269|PubMed:16908410}.
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 (PubMed:16319129).
CC Methylation is necessary for heterodimerization with FXR1, association
CC with polyribosomes, recruitment into stress granules and translation of
CC FMR1 target mRNAs. Methylated by PRMT1, PRMT3 and PRMT4, in vitro
CC (PubMed:16319129). {ECO:0000250|UniProtKB:Q06787,
CC ECO:0000269|PubMed:16319129}.
CC -!- DISRUPTION PHENOTYPE: Show normal fertility (PubMed:8033209). Display
CC enlarged testes and ovaries (PubMed:8033209, PubMed:23235829). Display
CC learning deficits and hyperactivity, in the absence of gross
CC pathological abnormalities of the brain (PubMed:8033209). Display
CC immature neurons with excess of long, thin growth cone filopodia and
CC dendritic filopodia and spine protrusions with less synaptic contacts
CC (PubMed:9144249, PubMed:11438589, PubMed:16631377, PubMed:17417632,
CC PubMed:18539120). Show no increase in the number of dendritic
CC filopodia-spine protrusions in response to KCL-mediated depolarization
CC (PubMed:16631377). Display alterations in the appearance, distribution
CC and volume of nuclear speckles (PubMed:24349419). Display enhanced
CC metabotropic glutamate receptor-dependent long-term depression (mGluR-
CC LTD) in the hippocampus (PubMed:11438589, PubMed:16908410,
CC PubMed:12032354). Leads to excessive presynaptic action potential (AP)
CC broadening in hippocampal and cortical neurons (PubMed:25561520). Show
CC alteration in the splicing pattern of its own FMR1 mRNA in the cortex
CC (PubMed:18653529). Alters the abundance and subcellular distribution of
CC a subset of mRNAs in the brain (PubMed:12575950, PubMed:17417632).
CC Display a reduction in the recruitment of certain FMR1 target mRNAs in
CC actively translating polyribosomes at synapses (PubMed:12575950,
CC PubMed:17507556). Display decreased delivery of specific mRNAs into
CC dendrites in mGluR-stimulated neurons (PubMed:18539120). Display a
CC delayed MAPB1 protein expression decline in the developing hippocampus
CC (PubMed:15475576). Show a relief of ribosome stalling on dendritic FMR1
CC target mRNAs (PubMed:21784246). Display enhanced postsynaptic protein
CC synthesis of a subset of FMR1 target mRNAs (PubMed:12581522,
CC PubMed:16908410, PubMed:19640847, PubMed:21784246). Unable to induce
CC postsynaptic protein synthesis of a subset of FMR1 mRNA targets in
CC response to mGluR activation (PubMed:16908410, PubMed:17507556).
CC Display enhanced presynaptic protein synthesis of the voltage-dependent
CC calcium channel CACNA1B (PubMed:24709664). Display also enhanced
CC protein synthesis of a subset of FMR1 target mRNAs in ovaries
CC (PubMed:23235829). Display reduced postsynaptic protein synthesis of a
CC subset of FMR1 target mRNAs (PubMed:12927206, PubMed:14614133,
CC PubMed:19640847, PubMed:19166269, PubMed:21490210). Display reduced
CC general protein synthesis in synapses in response to mGluR activation
CC (PubMed:15548614). Show brain-region specific reduction in the
CC expression and/or localization of FAM206A/Simiate (PubMed:24349419).
CC Display similar myelin basic protein (MBP) nexpression level in brain
CC cerebrum than in wild-type mice (PubMed:23891804). Display an absence
CC of nuclear foci on meiotic pachytene-stage chromosomes
CC (PubMed:24813610). Show incomplete resolution of single-strand repair
CC intermediates, crossing over and pairing of homologous chromosomes
CC during meiotic prophase in a subset of spermatocytes (PubMed:24813610).
CC {ECO:0000269|PubMed:11438589, ECO:0000269|PubMed:12032354,
CC ECO:0000269|PubMed:12575950, ECO:0000269|PubMed:12581522,
CC ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:14614133,
CC ECO:0000269|PubMed:15475576, ECO:0000269|PubMed:15548614,
CC ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:16908410,
CC ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:17507556,
CC ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:18653529,
CC ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:19640847,
CC ECO:0000269|PubMed:21490210, ECO:0000269|PubMed:21784246,
CC ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804,
CC ECO:0000269|PubMed:24349419, ECO:0000269|PubMed:24709664,
CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520,
CC ECO:0000269|PubMed:8033209, ECO:0000269|PubMed:9144249}.
CC -!- SIMILARITY: Belongs to the FMR1 family. {ECO:0000305}.
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DR EMBL; L23971; AAA37635.1; -; mRNA.
DR CCDS; CCDS30171.1; -. [P35922-1]
DR CCDS; CCDS72385.1; -. [P35922-3]
DR CCDS; CCDS90720.1; -. [P35922-7]
DR PIR; S36173; S36173.
DR AlphaFoldDB; P35922; -.
DR SMR; P35922; -.
DR CORUM; P35922; -.
DR IntAct; P35922; 242.
DR MINT; P35922; -.
DR STRING; 10090.ENSMUSP00000085906; -.
DR iPTMnet; P35922; -.
DR PhosphoSitePlus; P35922; -.
DR EPD; P35922; -.
DR MaxQB; P35922; -.
DR PaxDb; P35922; -.
DR PeptideAtlas; P35922; -.
DR PRIDE; P35922; -.
DR ProteomicsDB; 267374; -. [P35922-1]
DR ProteomicsDB; 267375; -. [P35922-2]
DR ProteomicsDB; 267376; -. [P35922-3]
DR ProteomicsDB; 267377; -. [P35922-4]
DR ProteomicsDB; 267378; -. [P35922-5]
DR ProteomicsDB; 267379; -. [P35922-6]
DR ProteomicsDB; 267380; -. [P35922-7]
DR ProteomicsDB; 267381; -. [P35922-8]
DR ProteomicsDB; 267382; -. [P35922-9]
DR ProteomicsDB; 267383; -. [P35922-10]
DR ProteomicsDB; 267384; -. [P35922-11]
DR ProteomicsDB; 267385; -. [P35922-12]
DR UCSC; uc009tiu.2; mouse. [P35922-1]
DR UCSC; uc009tiv.2; mouse. [P35922-11]
DR UCSC; uc009tiy.1; mouse. [P35922-5]
DR MGI; MGI:95564; Fmr1.
DR eggNOG; ENOG502QPKJ; Eukaryota.
DR InParanoid; P35922; -.
DR PhylomeDB; P35922; -.
DR ChiTaRS; Fmr1; mouse.
DR PRO; PR:P35922; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P35922; protein.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB.
DR GO; GO:0015030; C:Cajal body; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0010369; C:chromocenter; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0044326; C:dendritic spine neck; ISO:MGI.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; IDA:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:1990812; C:growth cone filopodium; IDA:UniProtKB.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:1990124; C:messenger ribonucleoprotein complex; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IDA:UniProtKB.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:0099523; C:presynaptic cytosol; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1990635; C:proximal dendrite; ISO:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IMP:SynGO.
DR GO; GO:0032797; C:SMN complex; ISO:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0097444; C:spine apparatus; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0070840; F:dynein complex binding; IDA:UniProtKB.
DR GO; GO:0002151; F:G-quadruplex RNA binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
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; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0043022; F:ribosome binding; ISO:MGI.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
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:MGI.
DR GO; GO:0045182; F:translation regulator activity; IMP:SynGO.
DR GO; GO:0030371; F:translation repressor activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0008089; P:anterograde axonal transport; IMP:SynGO.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0098586; P:cellular response to virus; ISO:MGI.
DR GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR GO; GO:0060996; P:dendritic spine development; IGI:MGI.
DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB.
DR GO; GO:0098976; P:excitatory chemical synaptic transmission; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; ISO:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; IDA:UniProtKB.
DR GO; GO:2000766; P:negative regulation of cytoplasmic translation; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1900453; P:negative regulation of long-term synaptic depression; IMP:UniProtKB.
DR GO; GO:1902373; P:negative regulation of mRNA catabolic process; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0010955; P:negative regulation of protein processing; ISO:MGI.
DR GO; GO:0002091; P:negative regulation of receptor internalization; ISO:MGI.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IDA:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; ISO:MGI.
DR GO; GO:1901254; P:positive regulation of intracellular transport of viral material; ISO:MGI.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; ISO:MGI.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:MGI.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IDA: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; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
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:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:MGI.
DR GO; GO:0045727; P:positive regulation of translation; IMP:CACAO.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0060998; P:regulation of dendritic spine development; IMP:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0060964; P:regulation of miRNA-mediated gene silencing; ISO:MGI.
DR GO; GO:1905244; P:regulation of modification of synaptic structure; IMP:SynGO.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR GO; GO:0098908; P:regulation of neuronal action potential; ISS:UniProtKB.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISS:UniProtKB.
DR GO; GO:0099578; P:regulation of translation at postsynapse, modulating synaptic transmission; IMP:SynGO.
DR GO; GO:0099577; P:regulation of translation at presynapse, modulating synaptic transmission; ISO:MGI.
DR GO; GO:0097396; P:response to interleukin-17; IMP:MGI.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0035176; P:social behavior; IMP:MGI.
DR GO; GO:0019226; P:transmission of nerve impulse; IMP:MGI.
DR Gene3D; 3.30.1370.10; -; 3.
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; Postsynaptic cell membrane; Reference proteome;
KW Repeat; Repressor; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Synapse; Synaptosome; Translation regulation;
KW Transport; Ubl conjugation.
FT CHAIN 1..614
FT /note="Fragile X messenger ribonucleoprotein 1"
FT /id="PRO_0000050103"
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 222..251
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 285..314
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 1..184
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000269|PubMed:8842725"
FT REGION 172..211
FT /note="Necessary for interaction with CYFIP1, CYFIP2, FXR1
FT and FXR2"
FT /evidence="ECO:0000250|UniProtKB:Q06787,
FT ECO:0000269|PubMed:11438699"
FT REGION 323..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..490
FT /note="Required for nuclear export"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT REGION 418..614
FT /note="Interaction with RANBP9"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT REGION 442..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..547
FT /note="RNA-binding RGG-box"
FT MOTIF 423..442
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:8842725"
FT MOTIF 526..533
FT /note="Nucleolar localization signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOTIF 595..599
FT /note="Nucleolar localization signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT COMPBIAS 499..536
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..570
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..603
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:0000250|UniProtKB:Q80WE1"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80WE1"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80WE1"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80WE1"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06787"
FT MOD_RES 462
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 470
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14570712"
FT MOD_RES 533
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 533
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 538
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 538
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 543
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 543
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 545
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 545
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:16319129"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 375..395
FT /note="Missing (in isoform 7, isoform 8, isoform 9, isoform
FT 10, isoform 11 and isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_002827"
FT VAR_SEQ 425..512
FT /note="EVDQLRLERLQIDEQLRQIGASSRPPPNRTDKEKGYVTDDGQGMGRGSRPYR
FT NRGHGRRGPGYTSGTNSEASNASETESDHRDELSDW -> LQQRKRGRASCAEETDGGV
FT EEEEEDKEEEEEEEASKETTIIPEQIIVHVIQERLKEEQLMDPCRVPPVKGAGCARVKI
FT VTRRRKSQTA (in isoform 6 and isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_002834"
FT VAR_SEQ 425..448
FT /note="EVDQLRLERLQIDEQLRQIGASSR -> ELILKHQMLLKQNLTTETNSVIGH
FT (in isoform 4 and isoform 10)"
FT /evidence="ECO:0000305"
FT /id="VSP_002831"
FT VAR_SEQ 425..436
FT /note="EVDQLRLERLQI -> NLTTETNSVIGH (in isoform 5 and
FT isoform 11)"
FT /evidence="ECO:0000305"
FT /id="VSP_002832"
FT VAR_SEQ 437..614
FT /note="Missing (in isoform 5 and isoform 11)"
FT /evidence="ECO:0000305"
FT /id="VSP_002833"
FT VAR_SEQ 449..614
FT /note="Missing (in isoform 4 and isoform 10)"
FT /evidence="ECO:0000305"
FT /id="VSP_002830"
FT VAR_SEQ 490..514
FT /note="Missing (in isoform 3 and isoform 9)"
FT /evidence="ECO:0000305"
FT /id="VSP_002829"
FT VAR_SEQ 490..501
FT /note="Missing (in isoform 2 and isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_002828"
FT VAR_SEQ 513..614
FT /note="Missing (in isoform 6 and isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_002835"
FT MUTAGEN 429..434
FT /note="LRLERL->ARAERA: Inhibits nuclear export."
FT /evidence="ECO:0000269|PubMed:8842725"
FT MUTAGEN 429..431
FT /note="LRL->ARA: Inhibits nuclear export."
FT /evidence="ECO:0000269|PubMed:8895584"
FT MUTAGEN 499
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:14570712"
FT MUTAGEN 499
FT /note="S->D: Leads to phosphorylation on other serine
FT residues."
FT /evidence="ECO:0000269|PubMed:14570712"
SQ SEQUENCE 614 AA; 68989 MW; 093DD90D589ED066 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 EIMPPSSLPS NNSRVGPNSS EEKKHLDTKE
NTHFSQPNST KVQRVLVVSS IVAGGPQKPE PKAWQGMVPF VFVGTKDSIA NATVLLDYHL
NYLKEVDQLR LERLQIDEQL RQIGASSRPP PNRTDKEKGY VTDDGQGMGR GSRPYRNRGH
GRRGPGYTSG TNSEASNASE TESDHRDELS DWSLAPTEEE RESFLRRGDG RRRRGGGRGQ
GGRGRGGGFK GNDDHSRTDN RPRNPREAKG RTADGSLQSA SSEGSRLRTG KDRNQKKEKP
DSVDGLQPLV NGVP
