ID FMR1_HUMAN Reviewed; 632 AA. AC Q06787; A6NNH4; D3DWT0; D3DWT1; D3DWT2; G8JL90; Q16578; Q5PQZ6; Q99054; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 235. 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:9659908}; DE AltName: Full=Protein FMR-1 {ECO:0000303|PubMed:1710175}; GN Name=FMR1 {ECO:0000303|PubMed:8504300, ECO:0000312|HGNC:HGNC:3775}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING. RC TISSUE=Fetal brain; RX PubMed=1710175; DOI=10.1016/0092-8674(91)90397-h; RA Verkerk A.J.M.H., Pieretti M., Sutcliffe J.S., Fu Y.H., Kuhl D.P., RA Pizzuti A., Reiner O., Richards S., Victoria M.F., Zhang F., Eussen B.E., RA van Ommen G.-J.B., Blonden L.A.J., Riggins G.J., Chastain J.L., Kunst C.B., RA Galjaard H., Caskey C.T., Nelson D.L., Oostra B.A., Warren S.T.; RT "Identification of a gene (FMR-1) containing a CGG repeat coincident with a RT breakpoint cluster region exhibiting length variation in fragile X RT syndrome."; RL Cell 65:905-914(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain, and Liver; RX PubMed=8504300; DOI=10.1093/hmg/2.4.399; RA Verkerk A.J.M.H., de Graaff E., de Boulle K., Eichler E.E., Konecki D.S., RA Reyniers E., Manca A., Poustka A., Willems P.J., Nelson D.L., Oostra B.A.; RT "Alternative splicing in the fragile X gene FMR1."; RL Hum. Mol. Genet. 2:399-404(1993). RN [3] RP ERRATUM OF PUBMED:8504300. RX PubMed=8401531; DOI=10.1093/hmg/2.8.1348; RA Verkerk A.J.H.M., de Graaff E., de Boulle K., Eichler E.E., Konecki D.S., RA Reyniers E., Manca A., Poustka A., Willems P.J., Nelson D.L., Oostra B.A.; RL Hum. Mol. Genet. 2:1348-1348(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9). RC TISSUE=Fetal brain; RX PubMed=24722188; DOI=10.1038/ncomms4650; RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A., RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.; RT "Protein interaction network of alternatively spliced isoforms from brain RT links genetic risk factors for autism."; RL Nat. Commun. 5:3650-3650(2014). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-34; 36-139; 141-293; 295-490 AND RP 492-632. RX PubMed=8401496; DOI=10.1093/hmg/2.8.1147; RA Eichler E.E., Richards S., Gibbs R.A., Nelson D.L.; RT "Fine structure of the human FMR1 gene."; RL Hum. Mol. Genet. 2:1147-1153(1993). RN [9] RP ERRATUM OF PUBMED:8401496. RX PubMed=8069329; RA Eichler E.E., Richards S., Gibbs R.A., Nelson D.L.; RL Hum. Mol. Genet. 3:684-685(1994). RN [10] RP SEQUENCE REVISION TO 18-34. RA Eichler E.E., Richards S., Gibbs R.A., Nelson D.L.; RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17. RX PubMed=7825604; DOI=10.1002/ajmg.1320560115; RA Hirst M., Grewal P., Flannery A., Slatter R., Maher E., Barton D., RA Fryns J.-P., Davies K.; RT "Two new cases of FMR1 deletion associated with mental impairment."; RL Am. J. Hum. Genet. 56:67-74(1995). RN [12] RP RNA-BINDING, AND INVOLVEMENT IN FXS. RX PubMed=7688265; DOI=10.1016/0092-8674(93)90420-u; RA Siomi H., Siomi M.C., Nussbaum R.L., Dreyfuss G.; RT "The protein product of the fragile X gene, FMR1, has characteristics of an RT RNA-binding protein."; RL Cell 74:291-298(1993). RN [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8515814; DOI=10.1038/363722a0; RA Verheij C., Bakker C.E., de Graaff E., Keulemans J., Willemsen R., RA Verkerk A.J.M.H., Galjaard H., Reuser A.J.J., Hoogeveen A.T., Oostra B.A.; RT "Characterization and localization of the FMR-1 gene product associated RT with fragile X syndrome."; RL Nature 363:722-724(1993). RN [14] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN FXS. RX PubMed=8401578; DOI=10.1038/ng0893-335; RA Devys D., Lutz Y., Rouyer N., Bellocq J.-P., Mandel J.-L.; RT "The FMR-1 protein is cytoplasmic, most abundant in neurons and appears RT normal in carriers of a fragile X premutation."; RL Nat. Genet. 4:335-340(1993). RN [15] RP ASSOCIATION IN MRNP, AND RNA-BINDING. RX PubMed=7692601; DOI=10.1126/science.7692601; RA Ashley C.T. Jr., Wilkinson K.D., Reines D., Warren S.T.; RT "FMR1 protein: conserved RNP family domains and selective RNA binding."; RL Science 262:563-566(1993). RN [16] RP RNA-BINDING, AND SUBCELLULAR LOCATION. RX PubMed=7781595; DOI=10.1002/j.1460-2075.1995.tb07237.x; RA Siomi M.C., Siomi H., Sauer W.H., Srinivasan S., Nussbaum R.L., RA Dreyfuss G.; RT "FXR1, an autosomal homolog of the fragile X mental retardation gene."; RL EMBO J. 14:2401-2408(1995). RN [17] RP SUBUNIT. RX PubMed=7489725; DOI=10.1002/j.1460-2075.1995.tb00220.x; RA Zhang Y., O'Connor J.P., Siomi M.C., Srinivasan S., Dutra A., RA Nussbaum R.L., Dreyfuss G.; RT "The fragile X mental retardation syndrome protein interacts with novel RT homologs FXR1 and FXR2."; RL EMBO J. 14:5358-5366(1995). RN [18] RP ALTERNATIVE SPLICING (ISOFORMS 6; 9; 10 AND 11), SUBCELLULAR LOCATION RP (ISOFORMS 6; 9; 10 AND 11), AND DOMAIN. RX PubMed=8789445; DOI=10.1093/hmg/5.1.95; RA Sittler A., Devys D., Weber C., Mandel J.L.; RT "Alternative splicing of exon 14 determines nuclear or cytoplasmic RT localisation of fmr1 protein isoforms."; RL Hum. Mol. Genet. 5:95-102(1996). RN [19] RP INTERACTION WITH FXR1 AND FXR2, AND ASSOCIATION WITH RIBOSOMES. RX PubMed=8668200; DOI=10.1128/mcb.16.7.3825; RA Siomi M.C., Zhang Y., Siomi H., Dreyfuss G.; RT "Specific sequences in the fragile X syndrome protein FMR1 and the FXR RT proteins mediate their binding to 60S ribosomal subunits and the RT interactions among them."; RL Mol. Cell. Biol. 16:3825-3832(1996). RN [20] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9259278; DOI=10.1093/hmg/6.8.1315; RA Tamanini F., Willemsen R., van Unen L., Bontekoe C., Galjaard H., RA Oostra B.A., Hoogeveen A.T.; RT "Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and RT testis."; RL Hum. Mol. Genet. 6:1315-1322(1997). RN [21] RP SUBCELLULAR LOCATION, ASSOCIATION WITH POLYRIBOSOME AND MRNP, AND RP CHARACTERIZATION OF VARIANT FXS ASN-304. RX PubMed=9659908; DOI=10.1016/s1097-2765(00)80012-x; RA Feng Y., Absher D., Eberhart D.E., Brown V., Malter H.E., Warren S.T.; RT "FMRP associates with polyribosomes as an mRNP, and the I304N mutation of RT severe fragile X syndrome abolishes this association."; RL Mol. Cell 1:109-118(1997). RN [22] RP INVOLVEMENT IN POF1. RX PubMed=9719368; DOI=10.1136/jmg.35.8.637; RA Murray A., Webb J., Grimley S., Conway G., Jacobs P.; RT "Studies of FRAXA and FRAXE in women with premature ovarian failure."; RL J. Med. Genet. 35:637-640(1998). RN [23] RP SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, AND CHARACTERIZATION OF RP VARIANT FXS ASN-304. RX PubMed=10196376; DOI=10.1093/hmg/8.5.863; RA Tamanini F., Bontekoe C., Bakker C.E., van Unen L., Anar B., Willemsen R., RA Yoshida M., Galjaard H., Oostra B.A., Hoogeveen A.T.; RT "Different targets for the fragile X-related proteins revealed by their RT distinct nuclear localizations."; RL Hum. Mol. Genet. 8:863-869(1999). RN [24] 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 [25] RP ASSOCIATION WITH POLYRIBOSOME. 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 [26] RP RNA-BINDING, AND DOMAIN. RX PubMed=11719189; DOI=10.1016/s0092-8674(01)00566-9; RA Darnell J.C., Jensen K.B., Jin P., Brown V., Warren S.T., Darnell R.B.; RT "Fragile X mental retardation protein targets G quartet mRNAs important for RT neuronal function."; RL Cell 107:489-499(2001). RN [27] RP FUNCTION, RNA-BINDING, AND DOMAIN. RX PubMed=11532944; DOI=10.1093/emboj/20.17.4803; RA Schaeffer C., Bardoni B., Mandel J.L., Ehresmann B., Ehresmann C., RA Moine H.; RT "The fragile X mental retardation protein binds specifically to its mRNA RT via a purine quartet motif."; RL EMBO J. 20:4803-4813(2001). RN [28] RP FUNCTION, INTERACTION WITH FXR1 AND FXR2, SUBUNIT, RNA-BINDING, AND RP CHARACTERIZATION OF VARIANT FXS ASN-304. RX PubMed=11157796; DOI=10.1093/hmg/10.4.329; RA Laggerbauer B., Ostareck D., Keidel E.M., Ostareck-Lederer A., Fischer U.; RT "Evidence that fragile X mental retardation protein is a negative regulator RT of translation."; RL Hum. Mol. Genet. 10:329-338(2001). RN [29] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12417522; DOI=10.1093/hmg/11.24.3007; RA Mazroui R., Huot M.E., Tremblay S., Filion C., Labelle Y., Khandjian E.W.; RT "Trapping of messenger RNA by Fragile X Mental Retardation protein into RT cytoplasmic granules induces translation repression."; RL Hum. Mol. Genet. 11:3007-3017(2002). RN [30] RP SUBCELLULAR LOCATION. RX PubMed=12417734; DOI=10.1128/mcb.22.23.8332-8341.2002; RA De Diego Otero Y., Severijnen L.A., van Cappellen G., Schrier M., RA Oostra B., Willemsen R.; RT "Transport of fragile X mental retardation protein via granules in neurites RT of PC12 cells."; RL Mol. Cell. Biol. 22:8332-8341(2002). RN [31] RP PHOSPHORYLATION AT SER-500, AND MUTAGENESIS OF SER-500. RX PubMed=12446764; DOI=10.1128/mcb.22.24.8438-8447.2002; RA Siomi M.C., Higashijima K., Ishizuka A., Siomi H.; RT "Casein kinase II phosphorylates the fragile X mental retardation protein RT and modulates its biological properties."; RL Mol. Cell. Biol. 22:8438-8447(2002). RN [32] RP SUBUNIT, RNA-BINDING, AND DOMAIN. RX PubMed=12950170; DOI=10.1021/bi034909g; RA Adinolfi S., Ramos A., Martin S.R., Dal Piaz F., Pucci P., Bardoni B., RA Mandel J.L., Pastore A.; RT "The N-terminus of the fragile X mental retardation protein contains a RT novel domain involved in dimerization and RNA binding."; RL Biochemistry 42:10437-10444(2003). RN [33] RP INTERACTION WITH NUFIP2, AND SUBCELLULAR LOCATION. RX PubMed=12837692; DOI=10.1093/hmg/ddg181; RA Bardoni B., Castets M., Huot M.-E., Schenck A., Adinolfi S., Corbin F., RA Pastore A., Khandjian E.W., Mandel J.-L.; RT "82-FIP, a novel FMRP (fragile X mental retardation protein) interacting RT protein, shows a cell cycle-dependent intracellular localization."; RL Hum. Mol. Genet. 12:1689-1698(2003). RN [34] RP INTERACTION WITH FXR1, SUBCELLULAR LOCATION, PHOSPHORYLATION, DOMAIN, AND RP MUTAGENESIS OF SER-500. RX PubMed=14532325; DOI=10.1093/hmg/ddg335; RA Mazroui R., Huot M.E., Tremblay S., Boilard N., Labelle Y., Khandjian E.W.; RT "Fragile X Mental Retardation protein determinants required for its RT association with polyribosomal mRNPs."; RL Hum. Mol. Genet. 12:3087-3096(2003). RN [35] RP FUNCTION, RNA-BINDING, AND ASSOCIATION WITH POLYRIBOSOME. RX PubMed=12594214; DOI=10.1074/jbc.m211117200; RA Sung Y.J., Dolzhanskaya N., Nolin S.L., Brown T., Currie J.R., Denman R.B.; RT "The fragile X mental retardation protein FMRP binds elongation factor 1A RT mRNA and negatively regulates its translation in vivo."; RL J. Biol. Chem. 278:15669-15678(2003). RN [36] RP INTERACTION WITH SND1. RX PubMed=14508492; DOI=10.1038/nature01956; RA Caudy A.A., Ketting R.F., Hammond S.M., Denli A.M., Bathoorn A.M., RA Tops B.B., Silva J.M., Myers M.M., Hannon G.J., Plasterk R.H.; RT "A micrococcal nuclease homologue in RNAi effector complexes."; RL Nature 425:411-414(2003). RN [37] RP FUNCTION, AND 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 [38] RP RNA-BINDING. 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 [39] RP INTERACTION WITH IGF2BP1, AND RNA-BINDING. RX PubMed=15282548; DOI=10.1038/sj.emboj.7600341; RA Rackham O., Brown C.M.; RT "Visualization of RNA-protein interactions in living cells: FMRP and IMP1 RT interact on mRNAs."; RL EMBO J. 23:3346-3355(2004). RN [40] RP RNA-BINDING, INTERACTION WITH RANBP9, SUBCELLULAR LOCATION, AND DOMAIN. 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 [41] RP FUNCTION, ASSOCIATION WITH MICRORNA, AND INTERACTION WITH AGO2. RX PubMed=14703574; DOI=10.1038/nn1174; RA Jin P., Zarnescu D.C., Ceman S., Nakamoto M., Mowrey J., Jongens T.A., RA Nelson D.L., Moses K., Warren S.T.; RT "Biochemical and genetic interaction between the fragile X mental RT retardation protein and the microRNA pathway."; RL Nat. Neurosci. 7:113-117(2004). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [43] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [44] RP INTERACTION WITH HABP4. RX PubMed=21771594; DOI=10.1016/j.febslet.2011.07.010; RA Goncalves K.A., Bressan G.C., Saito A., Morello L.G., Zanchin N.I., RA Kobarg J.; RT "Evidence for the association of the human regulatory protein Ki-1/57 with RT the translational machinery."; RL FEBS Lett. 585:2556-2560(2011). RN [45] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [48] RP CHARACTERIZATION OF VARIANT FXS ASN-304, RNA-BINDING, AND DOMAIN. 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 [49] RP METHYLATION AT ARG-544, AND MUTAGENESIS OF ARG-544 AND ARG-546. RX PubMed=16922515; DOI=10.1021/bi0525019; RA Dolzhanskaya N., Merz G., Denman R.B.; RT "Alternative splicing modulates protein arginine methyltransferase- RT dependent methylation of fragile X syndrome mental retardation protein."; RL Biochemistry 45:10385-10393(2006). RN [50] RP INTERACTION WITH MCRS1, ASSOCIATION WITH POLYRIBOSOME, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF SER-500. 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 [51] RP FUNCTION, RNA-BINDING, AND DOMAIN. RX PubMed=17057366; DOI=10.1155/jbb/2006/64347; RA Plante I., Davidovic L., Ouellet D.L., Gobeil L.A., Tremblay S., RA Khandjian E.W., Provost P.; RT "Dicer-derived microRNAs are utilized by the fragile X mental retardation RT protein for assembly on target RNAs."; RL J. Biomed. Biotechnol. 2006:64347-64347(2006). RN [52] RP METHYLATION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=16636078; DOI=10.1242/jcs.02882; RA Dolzhanskaya N., Merz G., Aletta J.M., Denman R.B.; RT "Methylation regulates the intracellular protein-protein and protein-RNA RT interactions of FMRP."; RL J. Cell Sci. 119:1933-1946(2006). RN [53] RP FUNCTION. 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 [54] RP RNA-BINDING. 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 [55] RP INTERACTION WITH TDRD3, AND SUBCELLULAR LOCATION. RX PubMed=18632687; DOI=10.1093/hmg/ddn203; RA Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J.; RT "TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic RT stress granules."; RL Hum. Mol. Genet. 17:3055-3074(2008). RN [56] RP SUBUNIT, INTERACTION WITH TDRD3, SUBCELLULAR LOCATION, AND CHARACTERIZATION RP OF VARIANT FXS ASN-304. RX PubMed=18664458; DOI=10.1093/hmg/ddn219; RA Linder B., Ploettner O., Kroiss M., Hartmann E., Laggerbauer B., RA Meister G., Keidel E., Fischer U.; RT "Tdrd3 is a novel stress granule-associated protein interacting with the RT Fragile-X syndrome protein FMRP."; RL Hum. Mol. Genet. 17:3236-3246(2008). RN [57] RP INTERACTION WITH SMN, ASSOCIATION WITH THE SMN CORE COMPLEX, SUBCELLULAR RP LOCATION, AND CHARACTERIZATION OF VARIANT FXS ASN-304. 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 [58] RP FUNCTION, AND RNA-BINDING. 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 [59] RP RNA-BINDING, AND DOMAIN. RX PubMed=18579868; DOI=10.1261/rna.1100708; RA Menon L., Mader S.A., Mihailescu M.R.; RT "Fragile X mental retardation protein interactions with the microtubule RT associated protein 1B RNA."; RL RNA 14:1644-1655(2008). RN [60] RP FUNCTION, RNA-BINDING, AND ASSOCIATION WITH POLYRIBOSOME AND MRNP. RX PubMed=19097999; DOI=10.1074/jbc.m807354200; RA Faehling M., Mrowka R., Steege A., Kirschner K.M., Benko E., Foerstera B., RA Persson P.B., Thiele B.J., Meier J.C., Scholz H.; RT "Translational regulation of the human achaete-scute homologue-1 by fragile RT X mental retardation protein."; RL J. Biol. Chem. 284:4255-4266(2009). RN [61] RP INTERACTION WITH NXF1, RNA-BINDING, AND SUBCELLULAR LOCATION. RX PubMed=18936162; DOI=10.1128/mcb.01377-08; RA Kim M., Bellini M., Ceman S.; RT "Fragile X mental retardation protein FMRP binds mRNAs in the nucleus."; RL Mol. Cell. Biol. 29:214-228(2009). RN [62] RP FUNCTION, RNA-BINDING, AND DOMAIN. 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 [63] 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 [64] RP FUNCTION, RNA-BINDING, AND CHARACTERIZATION OF VARIANT FXS ASN-304. 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 [65] RP LACK OF FUNCTION, 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 [66] RP FUNCTION (ISOFORMS 6 AND 10), SUBCELLULAR LOCATION (ISOFORMS 6; 9; 10 AND RP 11), PROTEOLYTIC PROCESSING (ISOFORM 10), RNA-BINDING (ISOFORMS 6 AND 10), RP DOMAIN (ISOFORM 10), TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT RP FXS ASN-304 (ISOFORM 10). RX PubMed=24204304; DOI=10.1371/journal.pgen.1003890; RA Dury A.Y., El Fatimy R., Tremblay S., Rose T.M., Cote J., De Koninck P., RA Khandjian E.W.; RT "Nuclear fragile X mental retardation protein is localized to Cajal RT bodies."; RL PLoS Genet. 9:E1003890-E1003890(2013). RN [67] RP FUNCTION, INTERACTION WITH METHYLATED HISTONE H3, DOMAIN, CHARACTERIZATION RP OF VARIANT FXS GLN-138, AND MUTAGENESIS OF THR-102 AND TYR-103. 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 [68] RP FUNCTION, INTERACTION WITH MOV10, AND RNA-BINDING. 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 [69] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH INFLUENZA A NP (MICROBIAL RP INFECTION), CHARACTERIZATION OF VARIANT FXS ASN-304 (MICROBIAL INFECTION), RP AND INDUCTION (MICROBIAL INFECTION). RX PubMed=24514761; DOI=10.1038/ncomms4259; RA Zhou Z., Cao M., Guo Y., Zhao L., Wang J., Jia X., Li J., Wang C., RA Gabriel G., Xue Q., Yi Y., Cui S., Jin Q., Wang J., Deng T.; RT "Fragile X mental retardation protein stimulates ribonucleoprotein assembly RT of influenza A virus."; RL Nat. Commun. 5:3259-3259(2014). RN [70] RP INTERACTION WITH CYFIP2; EIF5; NCL AND RPLP0 (ISOFORM 6), SUBCELLULAR RP LOCATION, DOMAIN, AND MUTAGENESIS OF 527-ARG--ARG-534 AND 613-GLN--LYS-617. RX PubMed=24658146; DOI=10.1371/journal.pone.0091465; RA Taha M.S., Nouri K., Milroy L.G., Moll J.M., Herrmann C., Brunsveld L., RA Piekorz R.P., Ahmadian M.R.; RT "Subcellular fractionation and localization studies reveal a direct RT interaction of the fragile X mental retardation protein (FMRP) with RT nucleolin."; RL PLoS ONE 9:E91465-E91465(2014). RN [71] RP RNA-BINDING, DOMAIN, AND MUTAGENESIS OF SER-500. 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 [72] RP INTERACTION WITH VENEZUELAN EQUINE ENCEPHALITIS VIRUS NON-STRUCTURAL RP PROTEIN 3 (MICROBIAL INFECTION). RX PubMed=27509095; DOI=10.1371/journal.ppat.1005810; RA Kim D.Y., Reynaud J.M., Rasalouskaya A., Akhrymuk I., Mobley J.A., RA Frolov I., Frolova E.I.; RT "New World and Old World Alphaviruses Have Evolved to Exploit Different RT Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral RT Replication Complexes."; RL PLoS Pathog. 12:E1005810-E1005810(2016). RN [73] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=31753916; DOI=10.1074/jbc.ac119.010078; RA Hsu P.J., Shi H., Zhu A.C., Lu Z., Miller N., Edens B.M., Ma Y.C., He C.; RT "The RNA-binding protein FMRP facilitates the nuclear export of N6- RT methyladenosine-containing mRNAs."; RL J. Biol. Chem. 294:19889-19895(2019). RN [74] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, METHYLATION, AND DOMAIN. RX PubMed=30765518; DOI=10.1073/pnas.1814385116; RA Tsang B., Arsenault J., Vernon R.M., Lin H., Sonenberg N., Wang L.Y., RA Bah A., Forman-Kay J.D.; RT "Phosphoregulated FMRP phase separation models activity-dependent RT translation through bidirectional control of mRNA granule formation."; RL Proc. Natl. Acad. Sci. U.S.A. 116:4218-4227(2019). RN [75] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CAPRIN1, PHOSPHORYLATION RP AT SER-460; SER-500; THR-502; SER-504; SER-511; SER-514; THR-518; THR-573; RP THR-574; THR-592; THR-594 AND THR-598, AND DOMAIN. RX PubMed=31439799; DOI=10.1126/science.aax4240; RA Kim T.H., Tsang B., Vernon R.M., Sonenberg N., Kay L.E., Forman-Kay J.D.; RT "Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates RT regulation of translation and deadenylation."; RL Science 365:825-829(2019). RN [76] RP STRUCTURE BY NMR OF 216-280. RX PubMed=9302998; DOI=10.1038/nsb0997-712; RA Musco G., Kharrat A., Stier G., Fraternali F., Gibson T.J., Nilges M., RA Pastore A.; RT "The solution structure of the first KH domain of FMR1, the protein RT responsible for the fragile X syndrome."; RL Nat. Struct. Biol. 4:712-716(1997). RN [77] RP STRUCTURE BY NMR OF 1-134, MUTAGENESIS OF 125-THR-PHE-126, SUBCELLULAR RP LOCATION, AND INTERACTION WITH NUFIP2. RX PubMed=16407062; DOI=10.1016/j.str.2005.09.018; RA Ramos A., Hollingworth D., Adinolfi S., Castets M., Kelly G., RA Frenkiel T.A., Bardoni B., Pastore A.; RT "The structure of the N-terminal domain of the fragile X mental retardation RT protein: a platform for protein-protein interaction."; RL Structure 14:21-31(2006). RN [78] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 397-425, AND CHARACTERIZATION OF RP VARIANT FXS ASN-304. RX PubMed=17850748; DOI=10.1016/j.str.2007.06.022; RA Valverde R., Pozdnyakova I., Kajander T., Venkatraman J., Regan L.; RT "Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of RT fragile X mental retardation protein."; RL Structure 15:1090-1098(2007). RN [79] RP VARIANT FXS ASN-304. RX PubMed=8490650; DOI=10.1038/ng0193-31; RA de Boulle K., Verkerk A.J.M.H., Reyniers E., Vits L., Hendrickx J., RA van Roy B., van den Bos F., de Graaff E., Oostra B.A., Willems P.J.; RT "A point mutation in the FMR-1 gene associated with fragile X mental RT retardation."; RL Nat. Genet. 3:31-35(1993). RN [80] RP CHARACTERIZATION OF VARIANT FXS ASN-304, AND RNA-BINDING. RX PubMed=8156595; DOI=10.1016/0092-8674(94)90232-1; RA Siomi H., Choi M., Siomi M.C., Nussbaum R.L., Dreyfuss G.; RT "Essential role for KH domains in RNA binding: impaired RNA binding by a RT mutation in the KH domain of FMR1 that causes fragile X syndrome."; RL Cell 77:33-39(1994). RN [81] RP CHARACTERIZATION OF VARIANT FXS ASN-304. RX PubMed=7633450; DOI=10.1093/hmg/4.5.895; RA Verheij C., de Graaff E., Bakker C.E., Willemsen R., Willems P.J., RA Meijer N., Galjaard H., Reuser A.J.J., Oostra B.A., Hoogeveen A.T.; RT "Characterization of FMR1 proteins isolated from different tissues."; RL Hum. Mol. Genet. 4:895-901(1995). RN [82] RP VARIANT HIS-546. RX PubMed=9375856; RX DOI=10.1002/(sici)1098-1004(1997)10:5<393::aid-humu10>3.0.co;2-v; RA Wang Y.-C., Lin M.-L., Lin S.J., Li Y.-C., Li S.-Y.; RT "Novel point mutation within intron 10 of FMR-1 gene causing fragile X RT syndrome."; RL Hum. Mutat. 10:393-399(1997). RN [83] RP INVOLVEMENT IN FXTAS. RX PubMed=11445641; DOI=10.1212/wnl.57.1.127; RA Hagerman R.J., Leehey M., Heinrichs W., Tassone F., Wilson R., Hills J., RA Grigsby J., Gage B., Hagerman P.J.; RT "Intention tremor, parkinsonism, and generalized brain atrophy in male RT carriers of fragile X."; RL Neurology 57:127-130(2001). RN [84] RP CHARACTERIZATION OF VARIANT FXS ASN-304, INTERACTION WITH FXR1 AND RPLP0, RP AND SUBCELLULAR LOCATION. RX PubMed=15380484; DOI=10.1016/j.expneurol.2004.05.039; RA Schrier M., Severijnen L.A., Reis S., Rife M., van't Padje S., RA van Cappellen G., Oostra B.A., Willemsen R.; RT "Transport kinetics of FMRP containing the I304N mutation of severe fragile RT X syndrome in neurites of living rat PC12 cells."; RL Exp. Neurol. 189:343-353(2004). RN [85] RP VARIANT GLN-138. RX PubMed=20799337; DOI=10.1002/ajmg.a.33626; RA Collins S.C., Bray S.M., Suhl J.A., Cutler D.J., Coffee B., Zwick M.E., RA Warren S.T.; RT "Identification of novel FMR1 variants by massively parallel sequencing in RT developmentally delayed males."; RL Am. J. Med. Genet. A 152:2512-2520(2010). RN [86] RP VARIANT FXS GLU-266, CHARACTERIZATION OF VARIANT FXS GLU-266, RNA-BINDING, RP AND ASSOCIATION WITH POLYRIBOSOME. RX PubMed=24448548; DOI=10.1038/ejhg.2013.311; RA Myrick L.K., Nakamoto-Kinoshita M., Lindor N.M., Kirmani S., Cheng X., RA Warren S.T.; RT "Fragile X syndrome due to a missense mutation."; RL Eur. J. Hum. Genet. 22:1185-1189(2014). RN [87] RP VARIANT FXS GLN-138, CHARACTERIZATION OF VARIANT FXS GLN-138, FUNCTION, RP INTERACTION WITH KCNMB4, AND DOMAIN. 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 target mRNAs (PubMed:12417522, PubMed:16631377, CC PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). CC Acts as an mRNA regulator by mediating formation of some phase- CC separated membraneless compartment: undergoes liquid-liquid phase CC separation upon binding to target mRNAs, leading to assemble mRNAs into CC cytoplasmic ribonucleoprotein granules that concentrate mRNAs with CC associated regulatory factors (PubMed:12417522, PubMed:30765518, CC PubMed:31439799). Plays a role in the alternative splicing of its own CC mRNA (PubMed:18653529). Stabilizes the scaffolding postsynaptic density CC protein DLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in CC hippocampal neurons and glial cells, respectively; this stabilization CC is further increased in response to metabotropic glutamate receptor CC (mGluR) stimulation (By similarity). Plays a role in selective delivery CC of a subset of dendritic mRNAs to synaptic sites in response to mGluR CC activation in a kinesin-dependent manner (By similarity). Undergoes CC liquid-liquid phase separation following phosphorylation and CC interaction with CAPRIN1, promoting formation of cytoplasmic CC ribonucleoprotein granules that concentrate mRNAs with factors that CC inhibit translation and mediate deadenylation of target mRNAs CC (PubMed:31439799). Acts as a repressor of mRNA translation in synaptic CC regions by mediating formation of neuronal ribonucleoprotein granules CC and promoting recruitmtent of EIF4EBP2 (PubMed:30765518). Plays a role CC as a repressor of mRNA translation during the transport of dendritic CC mRNAs to postsynaptic dendritic spines (PubMed:11532944, CC PubMed:11157796, PubMed:12594214, PubMed:23235829). Component of the CC CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation CC initiation (By similarity). Represses mRNA translation by stalling CC ribosomal translocation during elongation (By similarity). Reports are CC contradictory with regards to its ability to mediate translation CC inhibition of MBP mRNA in oligodendrocytes (PubMed:23891804). Also CC involved in the recruitment of the RNA helicase MOV10 to a subset of CC mRNAs and hence regulates microRNA (miRNA)-mediated translational CC repression by AGO2 (PubMed:14703574, PubMed:17057366, PubMed:25464849). CC Facilitates the assembly of miRNAs on specific target mRNAs CC (PubMed:17057366). Also plays a role as an activator of mRNA CC translation of a subset of dendritic mRNAs at synapses CC (PubMed:19097999, PubMed:19166269). 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 (PubMed:7692601, PubMed:11719189, CC PubMed:11157796, PubMed:12594214, PubMed:17417632, PubMed:23235829, CC PubMed:24448548). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA CC consensus sequences within mRNA targets, mainly at coding sequence CC (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR CC (PubMed:23235829). Binds to intramolecular G-quadruplex structures in CC the 5'- or 3'-UTRs of mRNA targets (PubMed:11719189, PubMed:18579868, CC PubMed:25464849, PubMed:25692235). Binds to G-quadruplex structures in CC the 3'-UTR of its own mRNA (PubMed:7692601, PubMed:11532944, CC PubMed:12594214, PubMed:15282548, PubMed:18653529). Binds also to RNA CC ligands harboring a kissing complex (kc) structure; this binding may CC mediate the association of FMR1 with polyribosomes (PubMed:15805463). CC Binds mRNAs containing U-rich target sequences (PubMed:12927206). Binds CC to a triple stem-loop RNA structure, called Sod1 stem loop interacting CC with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 CC mRNA (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 (By CC similarity). Plays a role in mRNA nuclear export (PubMed:31753916). CC Specifically recognizes and binds a subset of N6-methyladenosine (m6A)- CC containing mRNAs, promoting their nuclear export in a XPO1/CRM1- CC dependent manner (PubMed:31753916). Together with export factor NXF2, CC is involved in the regulation of the NXF1 mRNA stability in neurons (By CC similarity). Associates with export factor NXF1 mRNA-containing CC ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (By CC similarity). Binds to a subset of miRNAs in the brain (PubMed:14703574, CC PubMed:17057366). May associate with nascent transcripts in a nuclear CC protein NXF1-dependent manner (PubMed:18936162). 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) (PubMed:7688265, PubMed:7781595, CC PubMed:12950170, PubMed:15381419, PubMed:8156595). Moreover, plays a CC role 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 proteasomal degradation (By similarity). CC Plays a role in regulation of MAP1B-dependent microtubule dynamics CC during neuronal development (By similarity). 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:P35922, ECO:0000250|UniProtKB:Q80WE1, CC ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:11532944, CC ECO:0000269|PubMed:11719189, ECO:0000269|PubMed:12417522, CC ECO:0000269|PubMed:12594214, ECO:0000269|PubMed:12927206, CC ECO:0000269|PubMed:12950170, ECO:0000269|PubMed:14703574, CC ECO:0000269|PubMed:15282548, ECO:0000269|PubMed:15381419, CC ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:16631377, CC ECO:0000269|PubMed:17057366, ECO:0000269|PubMed:17417632, CC ECO:0000269|PubMed:18579868, ECO:0000269|PubMed:18653529, CC ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:19097999, CC ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:20512134, CC ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804, CC ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24813610, CC ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:25561520, CC ECO:0000269|PubMed:25692235, ECO:0000269|PubMed:30765518, CC ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:31753916, CC ECO:0000269|PubMed:7688265, ECO:0000269|PubMed:7692601, CC ECO:0000269|PubMed:7781595, ECO:0000269|PubMed:8156595}. CC -!- FUNCTION: [Isoform 10]: Binds to RNA homomer; preferentially on poly(G) CC and to a lesser extent on poly(U), but not on poly(A) or poly(C) CC (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). CC {ECO:0000269|PubMed:24204304}. CC -!- FUNCTION: [Isoform 6]: Binds to RNA homomer; preferentially on poly(G) CC and to a lesser extent on poly(U), but not on poly(A) or poly(C) CC (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). CC {ECO:0000269|PubMed:24204304}. CC -!- FUNCTION: (Microbial infection) Acts as a positive regulator of CC influenza A virus (IAV) replication. Required for the assembly and CC nuclear export of the viral ribonucleoprotein (vRNP) components. CC {ECO:0000269|PubMed:24514761}. CC -!- SUBUNIT: Homodimer (PubMed:7489725, PubMed:12950170, PubMed:16636078). CC Forms heterodimer with FXR1; heterodimerization occurs in a CC methylation-dependent manner (PubMed:7489725, PubMed:11157796, CC PubMed:16636078). Forms heterodimer with FXR2 (PubMed:7489725, CC PubMed:11157796). Homooligomer (PubMed:11157796, PubMed:18664458). CC Component of the CYFIP1-EIF4E-FMR1 complex at least composed of CYFIP, CC EIF4E and FMR1; this mRNA cap binding complex formation increases in CC presence of the brain cytoplasmic RNA BC1 and is dynamically regulated CC in an activity-dependent manner to repress and then possibly release CC dendritic mRNAs for translation in response to mGluR stimulation (By CC similarity). Associates with the SMN core complex that contains SMN, CC GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and CC STRAP/UNRIP (PubMed:18093976). Part of a ribonucleoprotein complex with CC AGO2/EIF2C2 and miRNAs (PubMed:14703574). Interacts with AGO2/EIF2C2 CC (PubMed:14703574). Interacts (via C-terminus) with CACNA1B; this CC interaction induces a decrease in the number of presynaptic functional CC CACNA1B channels at the cell surface (By similarity). Interacts with CC CYFIP1; this interaction recruits CYFIP1 to capped mRNA (By CC similarity). Interacts with CYFIP2 (By similarity). Interacts with CC EIF5; this interaction occurs in a RNA-dependent manner (By CC similarity). Interacts with dynein (By similarity). Interacts with FXR1 CC and FXR2 (PubMed:8668200, PubMed:14532325, PubMed:15380484). Interacts CC with methylated histone H3 (PubMed:24813610). Interacts with IGF2BP1; CC this interaction allows to recruit IGF2BP1 to mRNA in a FMR1-dependent CC manner (PubMed:15282548). Interacts (via N-terminus) with KCNMB4 CC (PubMed:25561520). Interacts with KCNT1 (via C-terminus); this CC interaction alters gating properties of KCNT1 (PubMed:20512134). CC Interacts (via phosphorylated form) with MCRS1 (via N-terminus) CC (PubMed:16571602). Interacts with MOV10; this interaction is direct, CC occurs in an RNA-dependent manner on polysomes and induces association CC of MOV10 with RNAs (PubMed:25464849). Interacts with MYO5A and PURA; CC these interactions occur in association with polyribosome (By CC similarity). Interacts with NCL (By similarity). Interacts with NUFIP1 CC (PubMed:10556305). Interacts (via N-terminus) with NUFIP2 CC (PubMed:12837692, PubMed:16407062). Interacts with NXF1; this CC interaction occurs in a mRNA-dependent and polyribosome-independent CC manner in the nucleus (PubMed:18936162). Interacts with NXF2 (via N- CC terminus); this interaction is direct and occurs in a NXF1 mRNA- CC containing mRNP complexes (By similarity). Interacts with RANBP9 (via CC C-terminus); this interaction is direct and inhibits binding of FMR1 to CC RNA homomer (PubMed:15381419). Interacts with RPLP0 (PubMed:15380484). CC Interacts (via C-terminus) with SMN (via C-terminus); this interaction CC is direct and occurs in a RNA-independent manner (PubMed:18093976). CC Interacts with TDRD3 (via C-terminus); this interaction is direct CC (PubMed:18632687, PubMed:18664458). Interacts with YBX1; this CC interaction occurs in association with polyribosome (By similarity). CC Interacts with nucleosome (PubMed:24813610). Associates with CC polyribosome; this association occurs in a mRNA-dependent manner CC (PubMed:9659908, PubMed:11719188, PubMed:12594214, PubMed:19097999, CC PubMed:24448548). Associates with cytoplasmic messenger CC ribonucleoprotein particles (mRNPs) (PubMed:7692601, PubMed:9659908, CC PubMed:12575950, PubMed:19097999). Associates with microtubules in a CC kinesin- and dynein-dependent manner (By similarity). Isoform 6 CC interacts (via N-terminus) with NCL (via C-terminus) (PubMed:24658146). CC Isoform 6 interacts with CYFIP2; this interaction occurs in a RNA- CC dependent manner (PubMed:24658146). Isoform 6 interacts with EIF5; this CC interaction occurs in a RNA-dependent manner (PubMed:24658146). Isoform CC 6 interacts with RPLP0 (PubMed:24658146). Interacts with HABP4 CC (PubMed:21771594). Interacts with SND1 (PubMed:14508492). Interacts CC (when phosphorylated by CK2) with CAPRIN1; interaction with CAPRIN1 CC promotes formation of a membraneless compartment (PubMed:31439799). CC {ECO:0000250|UniProtKB:P35922, ECO:0000269|PubMed:10556305, CC ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:11719188, CC ECO:0000269|PubMed:12575950, ECO:0000269|PubMed:12594214, CC ECO:0000269|PubMed:12837692, ECO:0000269|PubMed:12950170, CC ECO:0000269|PubMed:14508492, ECO:0000269|PubMed:14532325, CC ECO:0000269|PubMed:14703574, ECO:0000269|PubMed:15282548, CC ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:15381419, CC ECO:0000269|PubMed:16407062, ECO:0000269|PubMed:16571602, CC ECO:0000269|PubMed:16636078, ECO:0000269|PubMed:18093976, CC ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:18664458, CC ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:19097999, CC ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:21771594, CC ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24658146, CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25464849, CC ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:31439799, CC ECO:0000269|PubMed:7489725, ECO:0000269|PubMed:7692601, CC ECO:0000269|PubMed:8668200, ECO:0000269|PubMed:9659908}. CC -!- SUBUNIT: (Microbial infection) Interacts (via KH 2 domain) with CC influenza A nucleoprotein (NP); this interaction occurs in a RNA- CC dependent manner and stimulates viral ribonucleoprotein (vRNP) assembly CC and subsequent RNA synthesis. {ECO:0000269|PubMed:24514761}. CC -!- SUBUNIT: (Microbial infection) Interacts with Sindbis virus non- CC structural protein 3 (via C-terminus); this interaction inhibits the CC formation of host stress granules on viral mRNAs and the nsp3-FMR1 CC complexes bind viral RNAs and probably orchestrate the assembly of CC viral replication complexes. {ECO:0000269|PubMed:27509095}. CC -!- INTERACTION: CC Q06787; O00154: ACOT7; NbExp=2; IntAct=EBI-366305, EBI-948905; CC Q06787; Q7L576: CYFIP1; NbExp=4; IntAct=EBI-366305, EBI-1048143; CC Q06787; Q96F07: CYFIP2; NbExp=2; IntAct=EBI-366305, EBI-2433893; CC Q06787; Q06787: FMR1; NbExp=3; IntAct=EBI-366305, EBI-366305; CC Q06787; P51114: FXR1; NbExp=6; IntAct=EBI-366305, EBI-713291; CC Q06787; P51116: FXR2; NbExp=3; IntAct=EBI-366305, EBI-740459; CC Q06787; Q13283: G3BP1; NbExp=7; IntAct=EBI-366305, EBI-1047359; CC Q06787; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-366305, EBI-1210753; CC Q06787; P23246: SFPQ; NbExp=3; IntAct=EBI-366305, EBI-355453; CC Q06787-7; Q06481-5: APLP2; NbExp=3; IntAct=EBI-25856644, EBI-25646567; CC Q06787-7; Q14790: CASP8; NbExp=3; IntAct=EBI-25856644, EBI-78060; CC Q06787-7; Q86TI2-2: DPP9; NbExp=3; IntAct=EBI-25856644, EBI-21529239; CC Q06787-7; P19419: ELK1; NbExp=3; IntAct=EBI-25856644, EBI-726632; CC Q06787-7; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-25856644, EBI-6447163; CC Q06787-7; P08473: MME; NbExp=3; IntAct=EBI-25856644, EBI-353759; CC Q06787-7; P62714: PPP2CB; NbExp=3; IntAct=EBI-25856644, EBI-1044367; CC Q06787-7; P49768-2: PSEN1; NbExp=3; IntAct=EBI-25856644, EBI-11047108; CC Q06787-7; Q8TCT7-2: SPPL2B; NbExp=3; IntAct=EBI-25856644, EBI-8345366; CC Q06787-7; Q15583: TGIF1; NbExp=3; IntAct=EBI-25856644, EBI-714215; CC Q06787-7; P21980-2: TGM2; NbExp=3; IntAct=EBI-25856644, EBI-25842075; CC Q06787-7; P45880: VDAC2; NbExp=3; IntAct=EBI-25856644, EBI-354022; CC Q06787-7; O43257: ZNHIT1; NbExp=3; IntAct=EBI-25856644, EBI-347522; CC Q06787-8; A1L4K1: FSD2; NbExp=3; IntAct=EBI-10224470, EBI-5661036; CC Q06787-8; P51116: FXR2; NbExp=3; IntAct=EBI-10224470, EBI-740459; CC -!- SUBCELLULAR LOCATION: Cytoplasm, Cytoplasmic ribonucleoprotein granule CC {ECO:0000269|PubMed:12417734, ECO:0000269|PubMed:14532325, CC ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:16636078, CC ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:30765518, CC ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:9659908}. Cytoplasm, CC Stress granule {ECO:0000269|PubMed:12417522, CC ECO:0000269|PubMed:16636078, ECO:0000269|PubMed:18632687, CC ECO:0000269|PubMed:18664458}. Cytoplasm {ECO:0000269|PubMed:10196376, CC ECO:0000269|PubMed:12837692, ECO:0000269|PubMed:18664458, CC ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:7781595, CC ECO:0000269|PubMed:8401578, ECO:0000269|PubMed:8515814, CC ECO:0000269|PubMed:9259278}. Perikaryon {ECO:0000269|PubMed:12417734, CC ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:18093976}. Cytoplasm, CC perinuclear region {ECO:0000269|PubMed:24658146}. Cell projection, CC neuron projection {ECO:0000269|PubMed:12417734, CC ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:18093976}. Cell CC projection, axon {ECO:0000250|UniProtKB:P35922}. Cell projection, CC dendrite {ECO:0000250|UniProtKB:P35922}. Cell projection, dendritic CC spine {ECO:0000250|UniProtKB:P35922}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:P35922}. Cell projection, growth cone CC {ECO:0000269|PubMed:15380484}. Cell projection, filopodium tip CC {ECO:0000250|UniProtKB:P35922}. Synapse {ECO:0000250|UniProtKB:P35922}. CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:P35922}. Presynaptic CC cell membrane {ECO:0000250|UniProtKB:P35922}. Nucleus CC {ECO:0000269|PubMed:10196376, ECO:0000269|PubMed:16571602, CC ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:31753916}. Nucleus, CC nucleolus {ECO:0000269|PubMed:12837692, ECO:0000269|PubMed:16407062, CC ECO:0000269|PubMed:16571602, ECO:0000269|PubMed:24658146}. Chromosome, CC centromere {ECO:0000250|UniProtKB:P35922}. Chromosome CC {ECO:0000250|UniProtKB:P35922}. Cell membrane CC {ECO:0000250|UniProtKB:P35922}. Note=Mediates formation and localizes CC to cytoplasmic ribonucleoprotein membraneless compartments CC (PubMed:30765518, PubMed:31439799). Localizes to cytoplasmic CC ribonucleoprotein granules, also referred to as messenger CC ribonucleoprotein particles or mRNPs, along dendrites and dendritic CC spines (PubMed:9659908, PubMed:14532325). FMR1-containing cytoplasmic CC granules colocalize to F-actin-rich structures, including filopodium, CC spines and growth cone during the development of hippocampal neurons CC (By similarity). FMR1-containing cytoplasmic granules are transported CC out of the soma along axon and dendrite to synaptic contacts in a CC microtubule- and kinesin-dependent manner (PubMed:12417734, CC PubMed:15380484). Colocalizes with FXR1 and FXR2 in discrete granules, CC called fragile X granules (FXGs), along axon and presynaptic CC compartments (By similarity). Colocalizes with TDRD3 in cytoplasmic CC stress granules (SGs) in response to various cellular stress CC (PubMed:18632687, PubMed:18664458, PubMed:16636078). Colocalizes with CC FXR1, kinesin, 60S acidic ribosomal protein RPLP0 and SMN in CC cytoplasmic granules in the soma and neurite cell processes CC (PubMed:12417734, PubMed:18093976, PubMed:16636078). Colocalizes with CC H2AX/H2A.x in pericentromeric heterochromatin in response to DNA CC damaging agents (By similarity). Localizes on meiotic pachytene-stage CC chromosomes (By similarity). Forms nuclear foci representing sites of CC ongoing DNA replication in response to DNA damaging agents (By CC similarity). Shuttles between nucleus and cytoplasm in a XPO1/CRM1- CC dependent manner (PubMed:10196376). Colocalizes with CACNA1B in the CC cytoplasm and at the cell membrane of neurons (By similarity). CC Colocalizes with CYFIP1, CYFIP2, NXF2 and ribosomes in the perinuclear CC region (By similarity). Colocalizes with CYFIP1 and EIF4E in dendrites CC and probably at synapses (By similarity). CC {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q80WE1, CC ECO:0000269|PubMed:10196376, ECO:0000269|PubMed:12417734, CC ECO:0000269|PubMed:14532325, ECO:0000269|PubMed:15380484, CC ECO:0000269|PubMed:16636078, ECO:0000269|PubMed:18093976, CC ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:18664458, CC ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:31439799, CC ECO:0000269|PubMed:9659908}. CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm CC {ECO:0000269|PubMed:24204304, ECO:0000269|PubMed:8789445}. Cytoplasm, CC perinuclear region {ECO:0000269|PubMed:24204304}. CC -!- SUBCELLULAR LOCATION: [Isoform 9]: Cytoplasm CC {ECO:0000269|PubMed:24204304, ECO:0000269|PubMed:8789445}. CC -!- SUBCELLULAR LOCATION: [Isoform 10]: Nucleus CC {ECO:0000269|PubMed:8789445}. Nucleus, Cajal body CC {ECO:0000269|PubMed:24204304}. Note=Colocalizes with Colin and SMN in CC Cajal bodies (PubMed:24204304). CC -!- SUBCELLULAR LOCATION: [Isoform 11]: Nucleus CC {ECO:0000269|PubMed:8789445}. Nucleus, Cajal body CC {ECO:0000269|PubMed:24204304}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Comment=At least 12 different isoforms are produced.; CC Name=6; CC IsoId=Q06787-1; Sequence=Displayed; CC Name=1; CC IsoId=Q06787-2; Sequence=VSP_002823, VSP_002826; CC Name=2; CC IsoId=Q06787-3; Sequence=VSP_002824; CC Name=3; CC IsoId=Q06787-4; Sequence=VSP_002824, VSP_002826; CC Name=4; CC IsoId=Q06787-5; Sequence=VSP_002825; CC Name=5; CC IsoId=Q06787-6; Sequence=VSP_002825, VSP_002826; CC Name=7; CC IsoId=Q06787-7; Sequence=VSP_002826; CC Name=8; CC IsoId=Q06787-8; Sequence=VSP_002823, VSP_002825; CC Name=9; Synonyms=B; CC IsoId=Q06787-9; Sequence=VSP_002823; CC Name=10; Synonyms=ISO6 {ECO:0000303|PubMed:8789445}; CC IsoId=Q06787-10; Sequence=VSP_058423; CC Name=11; Synonyms=ISO12 {ECO:0000303|PubMed:8789445}; CC IsoId=Q06787-11; Sequence=VSP_002823, VSP_058423; CC -!- TISSUE SPECIFICITY: Expressed in the brain, cerebellum and testis CC (PubMed:8401578, PubMed:9259278). Also expressed in epithelial tissues CC (PubMed:8401578). Expressed in mature oligodendrocytes (OLGs) CC (PubMed:23891804). Expressed in fibroblast (PubMed:24204304). Expressed CC in neurons, Purkinje cells and spermatogonias (at protein level) CC (PubMed:8401578, PubMed:9259278). Expressed in brain, testis and CC placenta (PubMed:8504300, PubMed:9259278). Expressed in neurons and CC lymphocytes (PubMed:8504300). {ECO:0000269|PubMed:23891804, CC ECO:0000269|PubMed:24204304, ECO:0000269|PubMed:8401578, CC ECO:0000269|PubMed:8504300, ECO:0000269|PubMed:9259278}. CC -!- INDUCTION: (Microbial infection) Up-regulated in response to infection CC by influenza A virus. {ECO:0000269|PubMed:24514761}. CC -!- DOMAIN: The C-terminal disordered region undergoes liquid-liquid phase CC separation (LLPS) for the formation of a membraneless compartment that CC concentrates mRNAs with associated regulatory factors. CC {ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:31439799}. CC -!- DOMAIN: The N-terminal 134 amino acids are necessary for CC homodimerization and RNA-binding (PubMed:12950170). The N-terminal 298 CC amino acids are sufficient to interact with KCNMB4 and to regulate CC presynaptic action potential (AP) duration in neurons CC (PubMed:25561520). The two agenet-like domains are necessary for CC binding to histone H3 in a methylation-dependent manner CC (PubMed:24813610). The KH domains are necessary for mediating miRNA CC annealing to specific RNA targets (PubMed:17057366). The KH 2 domain is CC necessary for binding to kissing complex (kc) RNA ligands CC (PubMed:15805463). The RGG box domain is necessary for binding to mRNA CC targets that contain G-quadruplex structures (PubMed:11719189, CC PubMed:18579868, PubMed:25692235). The RGG-box domain is necessary for CC binding to a triple stem-loop RNA structure, called Sod1 stem loop CC interacting with FMRP (SoSLIP), in the superoxide dismutase SOD1 mRNA CC (PubMed:19166269). The RGG box domain is necessary for binding to its CC own mRNA (PubMed:11532944). The RGG-box domain is necessary for binding CC to homomer poly(G) (PubMed:14532325). {ECO:0000269|PubMed:11532944, CC ECO:0000269|PubMed:11719189, ECO:0000269|PubMed:12950170, CC ECO:0000269|PubMed:14532325, ECO:0000269|PubMed:15805463, CC ECO:0000269|PubMed:17057366, ECO:0000269|PubMed:18579868, CC ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:24813610, CC ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235}. CC -!- DOMAIN: [Isoform 10]: The C-terminal region contains a Cajal body CC localization signal at positions 490 through 506 (PubMed:24204304). CC {ECO:0000269|PubMed:24204304}. CC -!- PTM: Phosphorylated on several serine residues (PubMed:14532325). CC Phosphorylation by casein kinase II (CK2) promotes interaction with CC CAPRIN1 and liquid-liquid phase separation (LLPS) for the formation of CC a membraneless compartment that concentrates mRNAs with associated CC regulatory factors (PubMed:30765518, PubMed:31439799). Phosphorylation CC at Ser-500 by CK2 promotes secondary phosphorylation of other nearby CC serine residues (By similarity). Phosphorylation has no effect on the CC binding of individual mRNA species (By similarity). Unphosphorylated CC FMR1 is associated with actively translating polyribosome, whereas a CC fraction of phosphorylated FMR1 is associated with apparently stalled CC polyribosome (By similarity). Dephosphorylation by an activated CC phosphatase may release the FMR1-mediated translational repression and CC allow synthesis of a locally required protein at synapses (By CC similarity). {ECO:0000250|UniProtKB:P35922, CC ECO:0000269|PubMed:14532325, ECO:0000269|PubMed:30765518, CC ECO:0000269|PubMed:31439799}. 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 by PRMT1, PRMT3 and CC PRMT4 at four arginine residues of the arginine-glycine-glycine box CC (PubMed:16922515, PubMed:30765518). Methylation decreases ability to CC undergo liquid-liquid phase separation (LLPS) for the formation of a CC membraneless compartment (PubMed:30765518). Methylation does not affect CC mRNA-binding (PubMed:30765518). Methylation is necessary for CC heterodimerization with FXR1, association with polyribosomes, CC recruitment into stress granules and translation of FMR1 target mRNAs CC (PubMed:16636078). {ECO:0000269|PubMed:16636078, CC ECO:0000269|PubMed:16922515, ECO:0000269|PubMed:30765518}. CC -!- PTM: [Isoform 10]: Undergoes proteolytic cleavage; may be specifically CC cleaved by calpain-1/CAPN1 in cajal bodies (PubMed:24204304). CC {ECO:0000269|PubMed:24204304}. CC -!- DISEASE: Fragile X syndrome (FXS) [MIM:300624]: An X-linked dominant CC disease characterized by moderate to severe intellectual disability, CC macroorchidism (enlargement of the testicles), large ears, prominent CC jaw, and high-pitched, jocular speech. The defect in most patients CC results from an amplification of a CGG repeat region in the FMR1 gene CC and abnormal methylation. {ECO:0000269|PubMed:10196376, CC ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:15380484, CC ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:17850748, CC ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:18664458, CC ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:24204304, CC ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24514761, CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520, CC ECO:0000269|PubMed:7633450, ECO:0000269|PubMed:7688265, CC ECO:0000269|PubMed:8156595, ECO:0000269|PubMed:8401578, CC ECO:0000269|PubMed:8490650, ECO:0000269|PubMed:9659908}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Fragile X tremor/ataxia syndrome (FXTAS) [MIM:300623]: An X- CC linked neurodegenerative disorder characterized by late-onset, CC progressive cerebellar ataxia and intention tremor followed by CC cognitive decline. {ECO:0000269|PubMed:11445641}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Premature ovarian failure 1 (POF1) [MIM:311360]: An ovarian CC disorder defined as the cessation of ovarian function under the age of CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the CC presence of elevated levels of serum gonadotropins and low estradiol. CC {ECO:0000269|PubMed:9719368}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The mechanism of the severe phenotype in the Asn-304 CC patient lies in the sequestration of bound mRNAs in nontranslatable CC mRNP particles. In the absence of FMRP, these same mRNAs may be CC partially translated via alternate mRNPs, although perhaps abnormally CC localized or regulated, resulting in typical fragile X syndrome. Asn- CC 304 mutation maps to a position within the second KH domain of FMRP CC that is critical for stabilizing sequence-specific RNA-protein CC interactions. Asn-304 mutation abrogates the association of the FMRP KH CC 2 domain with its target, kissing complex RNA. CC -!- SIMILARITY: Belongs to the FMR1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA52458.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA62466.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=AAA62467.1; Type=Erroneous gene model prediction; 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; L29074; AAB18828.1; -; Genomic_DNA. DR EMBL; L29074; AAB18829.1; -; Genomic_DNA. DR EMBL; L29074; AAB18830.1; -; Genomic_DNA. DR EMBL; L29074; AAB18831.1; -; Genomic_DNA. DR EMBL; L29074; AAB18832.1; -; Genomic_DNA. DR EMBL; L29074; AAB18833.1; -; Genomic_DNA. DR EMBL; KJ534836; AHW56476.1; -; mRNA. DR EMBL; CH471171; EAW61294.1; -; Genomic_DNA. DR EMBL; CH471171; EAW61296.1; -; Genomic_DNA. DR EMBL; CH471171; EAW61298.1; -; Genomic_DNA. DR EMBL; CH471171; EAW61301.1; -; Genomic_DNA. DR EMBL; CH471171; EAW61302.1; -; Genomic_DNA. DR EMBL; CH471171; EAW61303.1; -; Genomic_DNA. DR EMBL; BC086957; AAH86957.1; -; mRNA. DR EMBL; M67468; AAA52458.1; ALT_INIT; mRNA. DR EMBL; X69962; CAA49586.1; -; mRNA. DR EMBL; S65791; AAB28395.2; -; mRNA. DR EMBL; L19476; AAA62452.2; -; Genomic_DNA. DR EMBL; L19477; AAA62453.1; -; Genomic_DNA. DR EMBL; L19478; AAA62454.1; -; Genomic_DNA. DR EMBL; L19479; AAA62455.1; -; Genomic_DNA. DR EMBL; L19480; AAA62456.1; -; Genomic_DNA. DR EMBL; L19481; AAA62457.1; -; Genomic_DNA. DR EMBL; L19482; AAA62458.1; -; Genomic_DNA. DR EMBL; L19483; AAA62459.1; -; Genomic_DNA. DR EMBL; L19484; AAA62460.1; -; Genomic_DNA. DR EMBL; L19485; AAA62461.1; -; Genomic_DNA. DR EMBL; L19486; AAA62462.1; -; Genomic_DNA. DR EMBL; L19487; AAA62463.1; -; Genomic_DNA. DR EMBL; L19488; AAA62464.1; -; Genomic_DNA. DR EMBL; L19489; AAA62465.1; -; Genomic_DNA. DR EMBL; L19490; AAA62466.1; ALT_SEQ; Genomic_DNA. DR EMBL; L19491; AAA62467.1; ALT_SEQ; Genomic_DNA. DR EMBL; L19492; AAA62468.1; -; Genomic_DNA. DR EMBL; L19493; AAA62469.1; -; Genomic_DNA. DR EMBL; S76590; AAD14228.1; -; Genomic_DNA. DR CCDS; CCDS14682.1; -. [Q06787-1] DR CCDS; CCDS55518.1; -. [Q06787-10] DR CCDS; CCDS55519.1; -. [Q06787-9] DR CCDS; CCDS76039.1; -. [Q06787-8] DR PIR; I68614; I68614. DR PIR; S45243; A40724. DR RefSeq; NP_001172004.1; NM_001185075.1. [Q06787-10] DR RefSeq; NP_001172005.1; NM_001185076.1. [Q06787-9] DR RefSeq; NP_001172010.1; NM_001185081.1. [Q06787-11] DR RefSeq; NP_001172011.1; NM_001185082.1. [Q06787-8] DR RefSeq; NP_002015.1; NM_002024.5. [Q06787-1] DR PDB; 2BKD; NMR; -; N=1-134. DR PDB; 2FMR; NMR; -; A=216-280. DR PDB; 2LA5; NMR; -; B=527-541. DR PDB; 2QND; X-ray; 1.90 A; A/B=216-425. DR PDB; 4OVA; X-ray; 3.00 A; A/B/C/D=1-209. DR PDB; 4QVZ; X-ray; 3.20 A; A/B=1-213. DR PDB; 4QW2; X-ray; 2.99 A; A/B=1-213. DR PDB; 5DE5; X-ray; 3.00 A; B/D=528-544. DR PDB; 5DE8; X-ray; 3.10 A; B/D=528-544. DR PDB; 5DEA; X-ray; 2.80 A; B/D=528-544. DR PDB; 5UWJ; X-ray; 2.22 A; D=423-437. DR PDB; 5UWO; X-ray; 2.35 A; D=422-438. DR PDBsum; 2BKD; -. DR PDBsum; 2FMR; -. DR PDBsum; 2LA5; -. DR PDBsum; 2QND; -. DR PDBsum; 4OVA; -. DR PDBsum; 4QVZ; -. DR PDBsum; 4QW2; -. DR PDBsum; 5DE5; -. DR PDBsum; 5DE8; -. DR PDBsum; 5DEA; -. DR PDBsum; 5UWJ; -. DR PDBsum; 5UWO; -. DR AlphaFoldDB; Q06787; -. DR SMR; Q06787; -. DR BioGRID; 108619; 296. DR ComplexPortal; CPX-2349; eIF4E-CYFIP1-FMRP translational repressor complex. DR DIP; DIP-29509N; -. DR IntAct; Q06787; 458. DR MINT; Q06787; -. DR STRING; 9606.ENSP00000359506; -. DR GlyGen; Q06787; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q06787; -. DR MetOSite; Q06787; -. DR PhosphoSitePlus; Q06787; -. DR BioMuta; FMR1; -. DR DMDM; 544328; -. DR EPD; Q06787; -. DR jPOST; Q06787; -. DR MassIVE; Q06787; -. DR MaxQB; Q06787; -. DR PaxDb; 9606-ENSP00000359506; -. DR PeptideAtlas; Q06787; -. DR ProteomicsDB; 34152; -. DR ProteomicsDB; 58477; -. [Q06787-1] DR ProteomicsDB; 58478; -. [Q06787-2] DR ProteomicsDB; 58479; -. [Q06787-3] DR ProteomicsDB; 58480; -. [Q06787-4] DR ProteomicsDB; 58481; -. [Q06787-5] DR ProteomicsDB; 58482; -. [Q06787-6] DR ProteomicsDB; 58483; -. [Q06787-7] DR ProteomicsDB; 58484; -. [Q06787-8] DR Pumba; Q06787; -. DR Antibodypedia; 3246; 834 antibodies from 45 providers. DR DNASU; 2332; -. DR Ensembl; ENST00000218200.12; ENSP00000218200.8; ENSG00000102081.16. [Q06787-9] DR Ensembl; ENST00000370470.5; ENSP00000359501.1; ENSG00000102081.16. [Q06787-6] DR Ensembl; ENST00000370471.7; ENSP00000359502.3; ENSG00000102081.16. [Q06787-10] DR Ensembl; ENST00000370475.9; ENSP00000359506.5; ENSG00000102081.16. [Q06787-1] DR Ensembl; ENST00000440235.6; ENSP00000413764.3; ENSG00000102081.16. [Q06787-8] DR Ensembl; ENST00000687593.1; ENSP00000509270.1; ENSG00000102081.16. [Q06787-2] DR Ensembl; ENST00000690137.1; ENSP00000509813.1; ENSG00000102081.16. [Q06787-7] DR GeneID; 2332; -. DR KEGG; hsa:2332; -. DR MANE-Select; ENST00000370475.9; ENSP00000359506.5; NM_002024.6; NP_002015.1. DR UCSC; uc004fck.5; human. [Q06787-1] DR AGR; HGNC:3775; -. DR CTD; 2332; -. DR DisGeNET; 2332; -. DR GeneCards; FMR1; -. DR GeneReviews; FMR1; -. DR HGNC; HGNC:3775; FMR1. DR HPA; ENSG00000102081; Low tissue specificity. DR MalaCards; FMR1; -. DR MIM; 300623; phenotype. DR MIM; 300624; phenotype. DR MIM; 309550; gene. DR MIM; 311360; phenotype. DR MIM; 616034; phenotype. DR neXtProt; NX_Q06787; -. DR OpenTargets; ENSG00000102081; -. DR Orphanet; 908; Fragile X syndrome. DR Orphanet; 642691; Fragile X-associated primary ovarian insufficiency. DR Orphanet; 93256; Fragile X-associated tremor/ataxia syndrome. DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure. DR Orphanet; 449291; Symptomatic form of fragile X syndrome in female carriers. DR Orphanet; 261483; Xq27.3q28 duplication syndrome. DR PharmGKB; PA28191; -. DR VEuPathDB; HostDB:ENSG00000102081; -. DR eggNOG; ENOG502QPKJ; Eukaryota. DR GeneTree; ENSGT00950000183189; -. DR HOGENOM; CLU_020699_4_0_1; -. DR InParanoid; Q06787; -. DR OMA; DQQQRGY; -. DR OrthoDB; 2995592at2759; -. DR PhylomeDB; Q06787; -. DR TreeFam; TF105427; -. DR PathwayCommons; Q06787; -. DR SignaLink; Q06787; -. DR SIGNOR; Q06787; -. DR BioGRID-ORCS; 2332; 14 hits in 777 CRISPR screens. DR ChiTaRS; FMR1; human. DR EvolutionaryTrace; Q06787; -. DR GeneWiki; FMR1; -. DR GenomeRNAi; 2332; -. DR Pharos; Q06787; Tbio. DR PRO; PR:Q06787; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q06787; Protein. DR Bgee; ENSG00000102081; Expressed in caput epididymis and 213 other cell types or tissues. DR ExpressionAtlas; Q06787; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB. DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB. DR GO; GO:0042995; C:cell projection; IDA:UniProtKB. 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; IDA:UniProtKB. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:1902737; C:dendritic filopodium; ISS:UniProtKB. DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB. DR GO; GO:0044326; C:dendritic spine neck; IBA:GO_Central. DR GO; GO:0032433; C:filopodium tip; ISS:UniProtKB. DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB. DR GO; GO:0030426; C:growth cone; IDA:UniProtKB. DR GO; GO:1990812; C:growth cone filopodium; ISS:UniProtKB. DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IDA:CAFA. 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; IBA:GO_Central. DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. 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:UniProtKB. DR GO; GO:0005844; C:polysome; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB. 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; ISS:UniProtKB. DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. 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; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB. DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProtKB. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB. DR GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:UniProtKB. DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB. DR GO; GO:1990247; F:N6-methyladenosine-containing RNA reader activity; IDA:UniProtKB. DR GO; GO:0008143; F:poly(A) binding; IEP:DisProt. DR GO; GO:0034046; F:poly(G) binding; IDA:UniProtKB. DR GO; GO:0008266; F:poly(U) RNA binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0043022; F:ribosome binding; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB. DR GO; GO:0033592; F:RNA strand annealing activity; IDA:UniProtKB. DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:UniProtKB. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProt. DR GO; GO:0035197; F:siRNA binding; IDA:UniProtKB. DR GO; GO:0031369; F:translation initiation factor binding; IPI:UniProtKB. DR GO; GO:0045182; F:translation regulator activity; IBA:GO_Central. DR GO; GO:0030371; F:translation repressor activity; IDA:UniProtKB. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0007215; P:glutamate receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; IMP:UniProtKB. DR GO; GO:0006406; P:mRNA export from nucleus; IDA:UniProtKB. 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:1900453; P:negative regulation of long-term synaptic depression; ISS:UniProtKB. DR GO; GO:0060965; P:negative regulation of miRNA-mediated gene silencing; IMP:UniProtKB. DR GO; GO:1902373; P:negative regulation of mRNA catabolic process; IMP:CAFA. 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; ISS:UniProtKB. DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW. DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; IDA:UniProtKB. 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:1901254; P:positive regulation of intracellular transport of viral material; IMP:UniProtKB. DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IDA: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; IBA:GO_Central. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB. DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB. DR GO; GO:0060998; P:regulation of dendritic spine development; IDA:UniProtKB. DR GO; GO:0051489; P:regulation of filopodium assembly; IDA:UniProtKB. DR GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB. DR GO; GO:0098908; P:regulation of neuronal action potential; IDA:UniProtKB. DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISS:UniProtKB. DR GO; GO:0031047; P:regulatory ncRNA-mediated gene silencing; IEA:UniProtKB-KW. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB. DR CDD; cd22506; KH_I_FMR1_rpt1; 1. DR CDD; cd22509; KH_I_FMR1_rpt2; 1. DR CDD; cd20471; Tudor_Agenet_FMR1_rpt1; 1. DR CDD; cd20474; Tudor_Agenet_FMR1_rpt2; 1. DR DisProt; DP00134; -. DR Gene3D; 2.30.30.140; -; 2. DR Gene3D; 3.30.1370.10; K Homology domain, type 1; 3. DR IDEAL; IID00719; -. DR InterPro; IPR008395; Agenet-like_dom. DR InterPro; IPR040148; FMR1. DR InterPro; IPR022034; FMR1-like_C_core. DR InterPro; IPR032196; FMR1_C2. DR InterPro; IPR040472; FMRP_KH0. DR InterPro; IPR004087; KH_dom. DR InterPro; IPR004088; KH_dom_type_1. DR InterPro; IPR036612; KH_dom_type_1_sf. DR InterPro; IPR047438; KH_I_FMR1_rpt1. DR InterPro; IPR047440; KH_I_FMR1_rpt2. DR InterPro; IPR047431; Tudor_Agenet_FMR1_rpt1. DR InterPro; IPR047436; Tudor_Agenet_FMR1_rpt2. DR InterPro; IPR041560; Tudor_FRM1. DR PANTHER; PTHR10603; FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN; 1. DR PANTHER; PTHR10603:SF4; SYNAPTIC FUNCTIONAL REGULATOR FMR1; 1. DR Pfam; PF05641; Agenet; 1. DR Pfam; PF16098; FXMR_C2; 1. 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; Eukaryotic type KH-domain (KH-domain type I); 2. DR PROSITE; PS51641; AGENET_LIKE; 2. DR PROSITE; PS50084; KH_TYPE_1; 2. DR Genevisible; Q06787; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Cell membrane; KW Cell projection; Centromere; Chromosome; Cytoplasm; Disease variant; KW DNA damage; Host-virus interaction; Intellectual disability; Membrane; KW Methylation; mRNA processing; mRNA splicing; mRNA transport; KW Neurodegeneration; Neurogenesis; Nucleus; Phosphoprotein; KW Postsynaptic cell membrane; Premature ovarian failure; Reference proteome; KW Repeat; Repressor; Ribonucleoprotein; RNA-binding; KW RNA-mediated gene silencing; Synapse; Synaptosome; Translation regulation; KW Transport; Ubl conjugation. FT CHAIN 1..632 FT /note="Fragile X messenger ribonucleoprotein 1" FT /id="PRO_0000050102" 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: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:0000269|PubMed:14532325, ECO:0000269|PubMed:8668200" FT REGION 325..349 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 397..491 FT /note="Required for nuclear export" FT /evidence="ECO:0000269|PubMed:18936162, FT ECO:0000269|PubMed:8789445" FT REGION 419..632 FT /note="Interaction with RANBP9" FT /evidence="ECO:0000269|PubMed:15381419" FT REGION 443..632 FT /note="Disordered" FT /evidence="ECO:0000269|PubMed:30765518, FT ECO:0000269|PubMed:31439799" FT REGION 534..548 FT /note="RNA-binding RGG-box" FT MOTIF 424..443 FT /note="Nuclear export signal" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOTIF 527..534 FT /note="Nucleolar localization signal 1" FT /evidence="ECO:0000269|PubMed:24658146" FT MOTIF 613..617 FT /note="Nucleolar localization signal 2" FT /evidence="ECO:0000269|PubMed:24658146" FT COMPBIAS 500..537 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 549..571 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 578..603 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 604..621 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 337 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80WE1" FT MOD_RES 370 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 460 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 463 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 471 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 500 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:12446764, FT ECO:0000269|PubMed:31439799, ECO:0007744|PubMed:24275569" FT MOD_RES 502 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 504 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 511 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 514 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 518 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 534 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 534 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 539 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 539 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 544 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 544 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000269|PubMed:16922515" FT MOD_RES 544 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 546 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 546 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35922" FT MOD_RES 573 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 574 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 592 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 594 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 598 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:31439799" FT MOD_RES 620 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35922" FT VAR_SEQ 376..396 FT /note="Missing (in isoform 1, isoform 8, isoform 9 and FT isoform 11)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:24722188, ECO:0000303|PubMed:8789445" FT /id="VSP_002823" FT VAR_SEQ 426..632 FT /note="EVDQLRLERLQIDEQLRQIGASSRPPPNRTDKEKSYVTDDGQGMGRGSRPYR FT NRGHGRRGPGYTSGTNSEASNASETESDHRDELSDWSLAPTEEERESFLRRGDGRRRGG FT GGRGQGGRGRGGGFKGNDDHSRTDNRPRNPREAKGRTTDGSLQIRVDCNNERSVHTKTL FT QNTSSEGSRLRTGKDRNQKKEKPDSVDGQQPLVNGVP -> LQQRKRGRASCAEETDGG FT VEGEEEDKEEEDVEEASKETTITPEQIIVHVIQERLKEEQQMDPFRSELTAIMKGVSTL FT KHYRIPPVKVVGCARVKIVTRRKRSQTAWMVSNHS (in isoform 10 and FT isoform 11)" FT /evidence="ECO:0000303|PubMed:8789445" FT /id="VSP_058423" FT VAR_SEQ 491..515 FT /note="Missing (in isoform 4, isoform 5 and isoform 8)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_002825" FT VAR_SEQ 491..502 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_002824" FT VAR_SEQ 580..596 FT /note="Missing (in isoform 1, isoform 3, isoform 5 and FT isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_002826" FT VARIANT 138 FT /note="R -> Q (in FXS; rare variant found in a FT developmentally delayed male; inhibits nucleosome binding; FT reduces interaction with KCNMB4; inhibits presynaptic FT action potential (AP) broadening; does not alter FT postsynaptic RNA-binding and polyribosome association; FT dbSNP:rs200163413)" FT /evidence="ECO:0000269|PubMed:20799337, FT ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520" FT /id="VAR_064507" FT VARIANT 145 FT /note="A -> S (in dbSNP:rs29281)" FT /id="VAR_029278" FT VARIANT 266 FT /note="G -> E (in FXS; reduces association with FT polyribosome; reduces RNA-binding; dbSNP:rs1569545763)" FT /evidence="ECO:0000269|PubMed:24448548" FT /id="VAR_075977" FT VARIANT 304 FT /note="I -> N (in FXS; alters protein folding and FT stability; increases nucleocytoplasmic shuttling; reduces FT localization in Cajal bodies; reduces the association with FT cytoplasmic granules; reduces association with FT polyribosome; reduces RNA-binding; attenuates mRNA FT translation repression; impairs homooligomerization; FT reduces interaction with TDRD3; reduces interaction with FT viral influenza A nucleoprotein (NP); does not inhibit FT interaction with SMN1, FXR1 and FXR2; dbSNP:rs121434622)" FT /evidence="ECO:0000269|PubMed:10196376, FT ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:15380484, FT ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:17850748, FT ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:18664458, FT ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:24204304, FT ECO:0000269|PubMed:24514761, ECO:0000269|PubMed:7633450, FT ECO:0000269|PubMed:8156595, ECO:0000269|PubMed:8490650, FT ECO:0000269|PubMed:9659908" FT /id="VAR_005234" FT VARIANT 546 FT /note="R -> H (in dbSNP:rs782651077)" FT /evidence="ECO:0000269|PubMed:9375856" FT /id="VAR_005235" FT MUTAGEN 102 FT /note="T->A: Reduces binding to nucleosome." FT /evidence="ECO:0000269|PubMed:24813610" FT MUTAGEN 103 FT /note="Y->L: Reduces binding to nucleosome." FT /evidence="ECO:0000269|PubMed:24813610" FT MUTAGEN 125..126 FT /note="TF->AA: Alters the structural integrity of the FT N-terminus and leads to aggregation." FT /evidence="ECO:0000269|PubMed:16407062" FT MUTAGEN 500 FT /note="S->A: Loss of phosphorylation. Does not affect FT interaction with MCRS1. Does not affect localization to FT cytoplasmic granules. Does not affect association with FT polyribosome." FT /evidence="ECO:0000269|PubMed:12446764, FT ECO:0000269|PubMed:14532325, ECO:0000269|PubMed:16571602" FT MUTAGEN 500 FT /note="S->D: Does not affect RNA-binding to G-quadruplex FT structure." FT /evidence="ECO:0000269|PubMed:25692235" FT MUTAGEN 527..534 FT /note="RRGDGRRR->EEGDGEEE: Reduces nucleolar localization. FT Strongly reduces nucleolar localization; when associated FT with 613-E--E-617." FT /evidence="ECO:0000269|PubMed:24658146" FT MUTAGEN 544 FT /note="R->K: Reduces arginine methylation by 80%." FT /evidence="ECO:0000269|PubMed:16922515" FT MUTAGEN 546 FT /note="R->K: Slightly reduced methylation." FT /evidence="ECO:0000269|PubMed:16922515" FT MUTAGEN 613..617 FT /note="QKKEK->EEEEE: Reduces nucleolar localization. FT Strongly reduces nucleolar localization; when associated FT with 527-E--E-534." FT /evidence="ECO:0000269|PubMed:24658146" FT CONFLICT 294..295 FT /note="Missing (in Ref. 1; AAA52458)" FT /evidence="ECO:0000305" FT STRAND 5..9 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 15..23 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 25..32 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 33..35 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 40..43 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 44..46 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 64..69 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 71..75 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 78..88 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 91..97 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 100..103 FT /evidence="ECO:0007829|PDB:4OVA" FT STRAND 104..108 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:4QW2" FT TURN 123..125 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 127..132 FT /evidence="ECO:0007829|PDB:4QW2" FT TURN 135..138 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 144..147 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 148..154 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:4QW2" FT TURN 163..166 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 167..173 FT /evidence="ECO:0007829|PDB:4QW2" FT HELIX 177..198 FT /evidence="ECO:0007829|PDB:4QW2" FT STRAND 220..224 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 230..234 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 239..245 FT /evidence="ECO:0007829|PDB:2QND" FT STRAND 250..256 FT /evidence="ECO:0007829|PDB:2QND" FT TURN 257..260 FT /evidence="ECO:0007829|PDB:2QND" FT STRAND 261..268 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 269..279 FT /evidence="ECO:0007829|PDB:2QND" FT STRAND 281..289 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 290..292 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 293..297 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 302..311 FT /evidence="ECO:0007829|PDB:2QND" FT STRAND 314..321 FT /evidence="ECO:0007829|PDB:2QND" FT STRAND 398..406 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 407..422 FT /evidence="ECO:0007829|PDB:2QND" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:5UWJ" FT STRAND 535..538 FT /evidence="ECO:0007829|PDB:2LA5" SQ SEQUENCE 632 AA; 71174 MW; F853D6C82E3489B9 CRC64; MEELVVEVRG SNGAFYKAFV KDVHEDSITV AFENNWQPDR QIPFHDVRFP PPVGYNKDIN ESDEVEVYSR ANEKEPCCWW LAKVRMIKGE FYVIEYAACD ATYNEIVTIE RLRSVNPNKP ATKDTFHKIK LDVPEDLRQM CAKEAAHKDF KKAVGAFSVT YDPENYQLVI LSINEVTSKR AHMLIDMHFR SLRTKLSLIM RNEEASKQLE SSRQLASRFH EQFIVREDLM GLAIGTHGAN IQQARKVPGV TAIDLDEDTC TFHIYGEDQD AVKKARSFLE FAEDVIQVPR NLVGKVIGKN GKLIQEIVDK SGVVRVRIEA ENEKNVPQEE EIMPPNSLPS NNSRVGPNAP EEKKHLDIKE NSTHFSQPNS TKVQRVLVAS SVVAGESQKP ELKAWQGMVP FVFVGTKDSI ANATVLLDYH LNYLKEVDQL RLERLQIDEQ LRQIGASSRP PPNRTDKEKS YVTDDGQGMG RGSRPYRNRG HGRRGPGYTS GTNSEASNAS ETESDHRDEL SDWSLAPTEE ERESFLRRGD GRRRGGGGRG QGGRGRGGGF KGNDDHSRTD NRPRNPREAK GRTTDGSLQI RVDCNNERSV HTKTLQNTSS EGSRLRTGKD RNQKKEKPDS VDGQQPLVNG VP //