FMR1_HUMAN
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 03-AUG-2022, entry version 226.
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: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, 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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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 [78]
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 [79]
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 [80]
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 [81]
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 [82]
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 a subset of mRNAs (PubMed:16631377, PubMed:18653529,
CC PubMed:19166269, PubMed:23235829, PubMed:25464849). Plays a role in the
CC alternative splicing of its own mRNA (PubMed:18653529). Plays a role in
CC mRNA nuclear export (By similarity). Together with export factor NXF2,
CC is involved in the regulation of the NXF1 mRNA stability in neurons (By
CC similarity). Stabilizes the scaffolding postsynaptic density protein
CC DLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in hippocampal
CC neurons and glial cells, respectively; this stabilization is further
CC increased in response to metabotropic glutamate receptor (mGluR)
CC stimulation (By similarity). Plays a role in selective delivery of a
CC subset of dendritic mRNAs to synaptic sites in response to mGluR
CC activation in a kinesin-dependent manner (By similarity). Plays a role
CC as a repressor of mRNA translation during the transport of dendritic
CC mRNAs to postsynaptic dendritic spines (PubMed: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). 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 proteosomal 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:12594214,
CC ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:12950170,
CC ECO:0000269|PubMed:14703574, ECO:0000269|PubMed:15282548,
CC ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15805463,
CC ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:17057366,
CC ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:18579868,
CC ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18936162,
CC ECO:0000269|PubMed:19097999, ECO:0000269|PubMed:19166269,
CC ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:23235829,
CC ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:24448548,
CC ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25464849,
CC ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235,
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).
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:7489725,
CC ECO:0000269|PubMed:7692601, ECO:0000269|PubMed:8668200,
CC 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=4; IntAct=EBI-366305, EBI-713291;
CC Q06787; P51116: FXR2; NbExp=3; IntAct=EBI-366305, EBI-740459;
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: Nucleus {ECO:0000269|PubMed:10196376,
CC ECO:0000269|PubMed:16571602, ECO:0000269|PubMed:18936162}. 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}. 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}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:24658146}. Cytoplasm,
CC Cytoplasmic ribonucleoprotein granule {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:9659908}. Perikaryon {ECO:0000269|PubMed:12417734,
CC ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:18093976}. Cell
CC projection, 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}. Cell membrane
CC {ECO:0000250|UniProtKB:P35922}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:16636078, ECO:0000269|PubMed:18632687,
CC ECO:0000269|PubMed:18664458}. Note=Colocalizes with H2AX/H2A.x in
CC pericentromeric heterochromatin in response to DNA damaging agents (By
CC similarity). Localizes on meiotic pachytene-stage chromosomes (By
CC similarity). Forms nuclear foci representing sites of ongoing DNA
CC replication in response to DNA damaging agents (By similarity).
CC Shuttles between nucleus and cytoplasm in a XPO1/CRM1-dependent manner
CC (PubMed:10196376). Localizes to cytoplasmic ribonucleoprotein granules,
CC also referred to as messenger ribonucleoprotein particles or mRNPs,
CC along dendrites and dendritic spines (PubMed:9659908, PubMed:14532325).
CC FMR1-containing cytoplasmic granules colocalize to F-actin-rich
CC structures, including filopodium, spines and growth cone during the
CC development of hippocampal neurons (By similarity). FMR1-containing
CC cytoplasmic granules are transported out of the soma along axon and
CC dendrite to synaptic contacts in a microtubule- and kinesin-dependent
CC manner (PubMed:12417734, PubMed:15380484). Colocalizes with CACNA1B in
CC the 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). Colocalizes with FXR1,
CC kinesin, 60S acidic ribosomal protein RPLP0 and SMN in cytoplasmic
CC granules in the soma and neurite cell processes (PubMed:12417734,
CC PubMed:18093976, PubMed:16636078). Colocalizes with FXR1 and FXR2 in
CC discrete granules, called fragile X granules (FXGs), along axon and
CC presynaptic compartments (By similarity). Colocalizes with TDRD3 in
CC cytoplasmic stress granules (SGs) in response to various cellular
CC stress (PubMed:18632687, PubMed:18664458, PubMed:16636078).
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: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). 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). Expressed in brain, testis and placenta
CC (PubMed:8504300). Expressed in neurons and lymphocytes
CC (PubMed:8504300). {ECO:0000269|PubMed:23891804,
CC ECO:0000269|PubMed:24204304, ECO:0000269|PubMed:8401578,
CC ECO:0000269|PubMed:8504300}.
CC -!- INDUCTION: (Microbial infection) Up-regulated in response to infection
CC by influenza A virus. {ECO:0000269|PubMed:24514761}.
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 (PubMed:14532325). Phosphorylated on several serine
CC residues. Phosphorylation at Ser-500 is required for phosphorylation of
CC other nearby serine residues. Phosphorylation has no effect on the
CC binding of individual mRNA species, but may affect the association with
CC polyribosome. Unphosphorylated FMR1 is associated with actively
CC translating polyribosome, whereas a fraction of phosphorylated FMR1 is
CC associated with apparently stalled polyribosome. Dephosphorylation by
CC an activated phosphatase may release the FMR1-mediated translational
CC repression and allow synthesis of a locally required protein at
CC snypases (By similarity). {ECO:0000250|UniProtKB:P35922,
CC ECO:0000269|PubMed:14532325}.
CC -!- PTM: Monoubiquitinated. Polyubiquitinated. Ubiquitinated and targeted
CC for proteasomal degradation after activation of metabotropic glutamate
CC receptor (mGluR). {ECO:0000250|UniProtKB:P35922}.
CC -!- PTM: Monomethylated and asymmetrically dimethylated at four arginine
CC residues of the arginine-glycine-glycine box. Methylation disrupts the
CC binding of FMRP to RNAs through its RGG box (By similarity).
CC Methylation is necessary for heterodimerization with FXR1, association
CC with polyribosomes, recruitment into stress granules and translation of
CC FMR1 target mRNAs (PubMed:16636078). Methylated by PRMT1, PRMT3 and
CC PRMT4, in vitro (PubMed:16922515). {ECO:0000250|UniProtKB:P35922,
CC ECO:0000269|PubMed:16636078, ECO:0000269|PubMed:16922515}.
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};
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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; 261.
DR DIP; DIP-29509N; -.
DR IntAct; Q06787; 360.
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; Q06787; -.
DR PeptideAtlas; Q06787; -.
DR PRIDE; 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 Antibodypedia; 3246; 764 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 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; 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; IGNDDHS; -.
DR OrthoDB; 374073at2759; -.
DR PhylomeDB; Q06787; -.
DR TreeFam; TF105427; -.
DR PathwayCommons; Q06787; -.
DR SignaLink; Q06787; -.
DR SIGNOR; Q06787; -.
DR BioGRID-ORCS; 2332; 12 hits in 705 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 211 other tissues.
DR ExpressionAtlas; Q06787; baseline and differential.
DR Genevisible; Q06787; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; IEA:UniProtKB-SubCell.
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:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:1990812; C:growth cone filopodium; ISS: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; ISS: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; IDA:UniProtKB.
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: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: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: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:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
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: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: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; IBA:GO_Central.
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: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:1902416; P:positive regulation of mRNA binding; 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:2001022; P:positive regulation of response to DNA damage stimulus; IBA:GO_Central.
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:0060964; P:regulation of miRNA-mediated gene silencing; IMP: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:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR DisProt; DP00134; -.
DR Gene3D; 3.30.1370.10; -; 3.
DR InterPro; IPR008395; Agenet-like_dom.
DR InterPro; IPR040148; FMR1.
DR InterPro; IPR040472; FMRP_KH0.
DR InterPro; IPR032196; FXMR_C2.
DR InterPro; IPR022034; FXMRP1_C_core.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR041560; Tudor_FRX1.
DR PANTHER; PTHR10603; PTHR10603; 1.
DR Pfam; PF05641; Agenet; 1.
DR Pfam; PF16098; FXMR_C2; 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; SSF54791; 2.
DR PROSITE; PS51641; AGENET_LIKE; 2.
DR PROSITE; PS50084; KH_TYPE_1; 2.
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:0000256|SAM:MobiDB-lite"
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 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"
FT /evidence="ECO:0000269|PubMed:12446764,
FT ECO:0007744|PubMed:24275569"
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 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 N-
FT 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
