Fmr1
entrez
14265
canonical
uniprot
P35922
canonical
ensembl
ENSMUSG00000000838
resolver
ensp
ENSMUSP00000085906
resolver
ensp
ENSMUSP00000110301
resolver
ensp
ENSMUSP00000110305
resolver
ensp
ENSMUSP00000283125
resolver
ensp
ENSMUSP00000283127
resolver
ensp
ENSMUSP00000283128
resolver
enst
ENSMUST00000114653
resolver
enst
ENSMUST00000114657
resolver
genesymbol
Fmr1
resolver
genesymbol_syn
Fmr-1
resolver
uniprot
E9QAT0
resolver
uniprot
E9QNF5
resolver
uniprot
Q547R0
resolver
uniprot
Q6AXB7
resolver
uniprot
Q8BPK8
resolver
uniprot_entry
E9QAT0_MOUSE
resolver
uniprot_entry
E9QNF5_MOUSE
resolver
uniprot_entry
FMR1_MOUSE
resolver
uniprot_entry
Q547R0_MOUSE
resolver
uniprot_entry
Q8BPK8_MOUSE
resolver
uniprot_sec
Q6AXB7
resolver
amino_acid_sequence
MEELVVEVRGSNGAFYKAFVKDVHEDSITVAFENNWQPERQIPFHDVRFPPPVGYNKDINESDEVEVYSRANEKEPCCWWLAKVRMIKGEFYVIEYAACDATYNEIVTIERLRSVNPNKPATKDTFHKIKLEVPEDLRQMCAKESAHKDFKKAVGAFSVTYDPENYQLVILSINEVTSKRAHMLIDMHFRSLRTKLSLILRNEEASKQLESSRQLASRFHEQFIVREDLMGLAIGTHGANIQQARKVPGVTAIDLDEDTCTFHIYGEDQDAVKKARSFLEFAEDVIQVPRNLVGKVIGKNGKLIQEIVDKSGVVRVRIEAENEKSVPQEEEIMPPSSLPSNNSRVGPNSSEEKKHLDTKENTHFSQPNSTKVQRVLVVSSIVAGGPQKPEPKAWQGMVPFVFVGTKDSIANATVLLDYHLNYLKEVDQLRLERLQIDEQLRQIGASSRPPPNRTDKEKGYVTDDGQGMGRGSRPYRNRGHGRRGPGYTSGTNSEASNASETESDHRDELSDWSLAPTEEERESFLRRGDGRRRGGGGRGQGGRGRGGGFKGNDDHSRTDNRPRNPREAKGRTADGSLQSASSEGSRLRTGKDRNQKKEKPDSVDGLQPLVNGVP
uniprot
proteins
function
FUNCTION: Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of target mRNAs (PubMed:11438589, PubMed:12032354, PubMed:15475576, PubMed:16631377, PubMed:16790844, PubMed:17417632, PubMed:17548835, PubMed:18539120, PubMed:18653529, PubMed:19166269, PubMed:19640847, PubMed:20159450, PubMed:21784246, PubMed:23235829, PubMed:24813610). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:12417522). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and the myelin basic protein MBP mRNAs in hippocampal neurons and glial cells, respectively; this stabilization is further increased in response to metabotropic glutamate receptor (mGluR) stimulation (PubMed:17417632). Undergoes liquid-liquid phase separation following phosphorylation and interaction with CAPRIN1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (By similarity). Acts as a repressor of mRNA translation in synaptic regions by mediating formation of neuronal ribonucleoprotein granules and promoting recruitmtent of EIF4EBP2 (By similarity). Plays a role in selective delivery of a subset of dendritic mRNAs to synaptic sites in response to mGluR activation in a kinesin-dependent manner (PubMed:18539120). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11376146, PubMed:12581522, PubMed:12927206, PubMed:14570712, PubMed:15475576, PubMed:16908410, PubMed:18805096, PubMed:19640847, PubMed:21784246, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (PubMed:18805096). Represses mRNA translation by stalling ribosomal translocation during elongation (PubMed:21784246). Reports are contradictory with regards to its ability to mediate translation inhibition of (MBP) mRNA in oligodendrocytes (PubMed:14613971, PubMed:23891804). Also involved in the recruitment of the RNA helicase MOV10 to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated translational repression by AGO2 (PubMed:20159450, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (By similarity). Also plays a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:14613971, PubMed:14614133, PubMed:15548614, PubMed:19166269, PubMed:19640847, PubMed:21490210). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (PubMed:16908410, PubMed:17507556, PubMed:19640847). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:11376146, PubMed:11719188, PubMed:14613971, PubMed:17507556, PubMed:21490210, PubMed:21784246, PubMed:24349419). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR (By similarity). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (By similarity). Also binds to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (By similarity). Binds mRNAs containing U-rich target sequences (By similarity). Binds to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA (PubMed:19166269). Binds to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses (PubMed:12581522, PubMed:18805096). Plays a role in mRNA nuclear export (PubMed:16790844, PubMed:31340148, PubMed:31753916). Specifically recognizes and binds a subset of N6-methyladenosine (m6A)-containing mRNAs, promoting their nuclear export in a XPO1/CRM1-dependent manner (PubMed:31340148, PubMed:31753916). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (PubMed:17548835). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (PubMed:17548835). Binds to a subset of miRNAs in the brain (PubMed:20159450). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (By similarity). In vitro, binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (By similarity). Moreover, plays a role in the modulation of the sodium-activated potassium channel KCNT1 gating activity (PubMed:20512134). Negatively regulates the voltage-dependent calcium channel current density in soma and presynaptic terminals of dorsal root ganglion (DRG) neurons, and hence regulates synaptic vesicle exocytosis (By similarity). Modulates the voltage-dependent calcium channel CACNA1B expression at the plasma membrane by targeting the channels for proteasomal degradation (PubMed:24709664). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (PubMed:15475576). Has been shown to play a translation-independent role in the modulation of presynaptic action potential (AP) duration and neurotransmitter release via large-conductance calcium-activated potassium (BK) channels in hippocampal and cortical excitatory neurons (PubMed:25561520). May be involved in the control of DNA damage response (DDR) mechanisms through the regulation of ATR-dependent signaling pathways such as histone H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates (By similarity). {ECO:0000250|UniProtKB:Q06787, ECO:0000250|UniProtKB:Q80WE1, ECO:0000269|PubMed:11376146, ECO:0000269|PubMed:11438589, ECO:0000269|PubMed:11719188, ECO:0000269|PubMed:12032354, ECO:0000269|PubMed:12417522, ECO:0000269|PubMed:12581522, ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:14570712, ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:14614133, ECO:0000269|PubMed:15475576, ECO:0000269|PubMed:15548614, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:16908410, ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:17507556, ECO:0000269|PubMed:17548835, ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:19640847, ECO:0000269|PubMed:20159450, ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:21490210, ECO:0000269|PubMed:21784246, ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:24349419, ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235, ECO:0000269|PubMed:31340148}.
uniprot
proteins
mass_dalton
68890
uniprot
proteins
mutagenesis
MUTAGEN 429..434; /note="LRLERL->ARAERA: Inhibits nuclear export."; /evidence="ECO:0000269|PubMed:8842725"; MUTAGEN 429..431; /note="LRL->ARA: Inhibits nuclear export."; /evidence="ECO:0000269|PubMed:8895584"; MUTAGEN 499; /note="S->A: Loss of phosphorylation."; /evidence="ECO:0000269|PubMed:14570712"; MUTAGEN 499; /note="S->D: Leads to phosphorylation on other serine residues."; /evidence="ECO:0000269|PubMed:14570712
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on several serine residues (PubMed:14570712, PubMed:27957526). Phosphorylation by casein kinase II (CK2) promotes interaction with CAPRIN1 and liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors (By similarity). Phosphorylation at Ser-499 by CK2 promotes secondary phosphorylation of other nearby serine residues (PubMed:14570712, PubMed:27957526). Phosphorylation has no effect on the binding of individual mRNA species (PubMed:14570712). Unphosphorylated FMR1 is associated with actively translating polyribosome, whereas a fraction of phosphorylated FMR1 is associated with apparently stalled polyribosome (PubMed:14570712). Dephosphorylation by an activated phosphatase may release the FMR1-mediated translational repression and allow synthesis of a locally required protein at synapses (PubMed:14570712). {ECO:0000250|UniProtKB:Q06787, ECO:0000269|PubMed:14570712, ECO:0000269|PubMed:27957526}.; PTM: Monoubiquitinated (PubMed:16908410). Polyubiquitinated (PubMed:16908410). Ubiquitinated and targeted for proteasomal degradation after activation of metabotropic glutamate receptor (mGluR) (PubMed:16908410). {ECO:0000269|PubMed:16908410}.; PTM: Monomethylated and asymmetrically dimethylated by PRMT1, PRMT3 and PRMT4 at four arginine residues of the arginine-glycine-glycine box (PubMed:16319129). Methylation decreases ability to undergo liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment (By similarity). Methylation does not affect mRNA-binding (By similarity). Methylation is necessary for heterodimerization with FXR1, association with polyribosomes, recruitment into stress granules and translation of FMR1 target mRNAs (By similarity). {ECO:0000250|UniProtKB:Q06787, ECO:0000269|PubMed:16319129}.
uniprot
proteins
protein_family
FMR1 family
uniprot
proteins
pubmed
10556305
uniprot
proteins
pubmed
10567518
uniprot
proteins
pubmed
11162447
uniprot
proteins
pubmed
11376146
uniprot
proteins
pubmed
11438589
uniprot
proteins
pubmed
11438699
uniprot
proteins
pubmed
11719188
uniprot
proteins
pubmed
12032354
uniprot
proteins
pubmed
12147688
uniprot
proteins
pubmed
12417522
uniprot
proteins
pubmed
12575950
uniprot
proteins
pubmed
12581522
uniprot
proteins
pubmed
12927206
uniprot
proteins
pubmed
14570712
uniprot
proteins
pubmed
14613971
uniprot
proteins
pubmed
14614133
uniprot
proteins
pubmed
15028757
uniprot
proteins
pubmed
15312650
uniprot
proteins
pubmed
15317853
uniprot
proteins
pubmed
15329415
uniprot
proteins
pubmed
15381419
uniprot
proteins
pubmed
15475576
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15548614
uniprot
proteins
pubmed
15805463
uniprot
proteins
pubmed
16000371
uniprot
proteins
pubmed
16098134
uniprot
proteins
pubmed
16319129
uniprot
proteins
pubmed
16631377
uniprot
proteins
pubmed
16675531
uniprot
proteins
pubmed
16790844
uniprot
proteins
pubmed
16908410
uniprot
proteins
pubmed
17417632
uniprot
proteins
pubmed
17507556
uniprot
proteins
pubmed
17548835
uniprot
proteins
pubmed
18093976
uniprot
proteins
pubmed
18539120
uniprot
proteins
pubmed
18653529
uniprot
proteins
pubmed
18805096
uniprot
proteins
pubmed
19166269
uniprot
proteins
pubmed
19193898
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19640847
uniprot
proteins
pubmed
20159450
uniprot
proteins
pubmed
20512134
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21490210
uniprot
proteins
pubmed
21784246
uniprot
proteins
pubmed
23235829
uniprot
proteins
pubmed
23891804
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24349419
uniprot
proteins
pubmed
24709664
uniprot
proteins
pubmed
24813610
uniprot
proteins
pubmed
25464849
uniprot
proteins
pubmed
25561520
uniprot
proteins
pubmed
25692235
uniprot
proteins
pubmed
27770568
uniprot
proteins
pubmed
27957526
uniprot
proteins
pubmed
31340148
uniprot
proteins
pubmed
31753916
uniprot
proteins
pubmed
8033209
uniprot
proteins
pubmed
8358432
uniprot
proteins
pubmed
8842725
uniprot
proteins
pubmed
8895584
uniprot
proteins
pubmed
9144249
uniprot
proteins
pubmed
9259278
uniprot
proteins
pubmed
9285783
uniprot
proteins
sequence_length
614
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, Cytoplasmic ribonucleoprotein granule {ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:15312650, ECO:0000269|PubMed:15329415, ECO:0000269|PubMed:16098134, ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:9285783}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q06787}. Nucleus {ECO:0000269|PubMed:16908410, ECO:0000269|PubMed:31340148, ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:8895584}. Nucleus, nucleolus {ECO:0000250|UniProtKB:Q06787}. Chromosome, centromere {ECO:0000269|PubMed:24813610}. Chromosome {ECO:0000269|PubMed:24813610}. Cytoplasm {ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:14570712, ECO:0000269|PubMed:15317853, ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:8895584}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:9285783}. Perikaryon {ECO:0000269|PubMed:14613971, ECO:0000269|PubMed:16908410, ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19193898}. Cell projection, neuron projection {ECO:0000250|UniProtKB:Q06787}. Cell projection, axon {ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:19193898}. Cell projection, dendrite {ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:16908410, ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19193898}. Cell projection, dendritic spine {ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:16631377}. Synapse, synaptosome {ECO:0000269|PubMed:18805096}. Cell projection, filopodium {ECO:0000269|PubMed:16631377}. Cell projection, growth cone {ECO:0000269|PubMed:16631377}. Cell projection, filopodium tip {ECO:0000269|PubMed:16631377}. Synapse {ECO:0000269|PubMed:16631377}. Postsynaptic cell membrane {ECO:0000269|PubMed:19193898, ECO:0000269|PubMed:27770568}. Presynaptic cell membrane {ECO:0000269|PubMed:19193898, ECO:0000269|PubMed:27770568}. Cell membrane {ECO:0000269|PubMed:24709664}. Note=Mediates formation and localizes to cytoplasmic ribonucleoprotein membraneless compartments (By similarity). Localizes to cytoplasmic granules, also referred to as messenger ribonucleoprotein particles or mRNPs, along dendrites and dendritic spines (PubMed:15028757, PubMed:16631377). FMR1-containing cytoplasmic granules colocalize to F-actin-rich structures, including filopodium, spines and growth cone during the development of hippocampal neurons (By similarity). FMR1-containing cytoplasmic granules are transported out of the soma along axon and dendrite to synaptic contacts in a microtubule- and kinesin-dependent manner (PubMed:15312650, PubMed:16098134, PubMed:18539120). Colocalizes with FXR1 and FXR2 in discrete granules, called fragile X granules (FXGs), along axon and presynaptic compartments (PubMed:19193898). Colocalizes with TDRD3 in cytoplasmic stress granules (SGs) in response to various cellular stress (By similarity). Colocalizes with H2AX/H2A.x in pericentromeric heterochromatin in response to DNA damaging agents (PubMed:24813610). Localizes on meiotic pachytene-stage chromosomes (PubMed:24813610). Forms nuclear foci representing sites of ongoing DNA replication in response to DNA damaging agents (PubMed:24813610). Shuttles between nucleus and cytoplasm in a XPO1/CRM1-dependent manner (PubMed:8842725, PubMed:8895584). Colocalizes with CACNA1B in the cytoplasm and at the cell membrane of neurons (PubMed:24709664). Colocalizes with CYFIP1, CYFIP2, NXF2 and ribosomes in the perinuclear region (PubMed:11438699, PubMed:16790844). Colocalizes with CYFIP1 and EIF4E in dendrites and probably at synapses (PubMed:18805096). Colocalizes with FXR1, kinesin, 60S acidic ribosomal protein RPLP0 and SMN in cytoplasmic granules in the soma and neurite cell processes (By similarity). {ECO:0000250|UniProtKB:Q06787, ECO:0000250|UniProtKB:Q80WE1, ECO:0000269|PubMed:11438699, ECO:0000269|PubMed:15028757, ECO:0000269|PubMed:15312650, ECO:0000269|PubMed:16098134, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:16790844, ECO:0000269|PubMed:18539120, ECO:0000269|PubMed:18805096, ECO:0000269|PubMed:19193898, ECO:0000269|PubMed:24709664, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:8842725, ECO:0000269|PubMed:8895584}.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus {ECO:0000269|PubMed:8842725}. Nucleus, nucleoplasm {ECO:0000269|PubMed:8842725}.
uniprot
proteins