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Protein

Synaptic functional regulator FMR1

Gene

Fmr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 a subset of mRNAs (PubMed:11438589, PubMed:12032354, PubMed:15475576, PubMed:16631377, PubMed:16790844, PubMed:17417632, PubMed:17548835, PubMed:18539120, PubMed:18653529, PubMed:19640847, PubMed:19166269, PubMed:20159450, PubMed:21784246, PubMed:23235829, PubMed:24813610). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Plays a role in mRNA nuclear export (PubMed:16790844). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (PubMed:17548835). 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). 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 postnyaptic dendritic spines (PubMed:11376146, PubMed:12581522, PubMed:14570712, PubMed:12927206, 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). Plays also a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:14614133, PubMed:14613971, PubMed:15548614, PubMed:19640847, PubMed:19166269, 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:11719188, PubMed:11376146, PubMed:14613971, PubMed:17507556, PubMed:21784246, PubMed:21490210, 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). Binds also 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). 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 homopolymer; 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 proteosomal degradation (PubMed:24709664). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (PubMed:15475576). Recently, 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). Finally, FMR1 may be involved in the control of DNA damage response (DDR) mechanisms through the regulation of ATR-dependent signaling pathways such as histone H2AFX/H2A.x and BRCA1 phosphorylations (PubMed:24813610).By similarity33 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • dynein binding Source: UniProtKB
  • G-quadruplex RNA binding Source: UniProtKB
  • identical protein binding Source: MGI
  • ion channel binding Source: MGI
  • methylated histone binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • miRNA binding Source: UniProtKB
  • mRNA 3'-UTR binding Source: UniProtKB
  • mRNA 5'-UTR binding Source: UniProtKB
  • mRNA binding Source: UniProtKB
  • poly(A) RNA binding Source: MGI
  • poly(G) binding Source: UniProtKB
  • poly(U) RNA binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ribosome binding Source: MGI
  • RNA binding Source: MGI
  • RNA stem-loop binding Source: UniProtKB
  • RNA strand annealing activity Source: UniProtKB
  • sequence-specific mRNA binding Source: UniProtKB
  • siRNA binding Source: UniProtKB
  • translation initiation factor binding Source: MGI
  • translation repressor activity Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to hydroxyurea Source: UniProtKB
  • cellular response to UV Source: UniProtKB
  • cellular response to virus Source: MGI
  • central nervous system development Source: MGI
  • dendritic spine development Source: MGI
  • gene silencing by RNA Source: UniProtKB-KW
  • glutamate receptor signaling pathway Source: UniProtKB
  • modulation by host of viral RNA genome replication Source: MGI
  • mRNA processing Source: UniProtKB-KW
  • mRNA transport Source: UniProtKB
  • negative regulation of cytoplasmic translation Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of long term synaptic depression Source: UniProtKB
  • negative regulation of synaptic vesicle exocytosis Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • negative regulation of translational initiation Source: UniProtKB
  • negative regulation of voltage-gated calcium channel activity Source: UniProtKB
  • positive regulation of dendritic spine development Source: UniProtKB
  • positive regulation of filopodium assembly Source: UniProtKB
  • positive regulation of gene silencing by miRNA Source: UniProtKB
  • positive regulation of histone phosphorylation Source: UniProtKB
  • positive regulation of intracellular transport of viral material Source: MGI
  • positive regulation of mRNA binding Source: UniProtKB
  • positive regulation of proteasomal protein catabolic process Source: UniProtKB
  • positive regulation of receptor internalization Source: UniProtKB
  • positive regulation of response to DNA damage stimulus Source: UniProtKB
  • positive regulation of translation Source: UniProtKB
  • regulation of alternative mRNA splicing, via spliceosome Source: UniProtKB
  • regulation of dendritic spine development Source: UniProtKB
  • regulation of filopodium assembly Source: UniProtKB
  • regulation of gene silencing by miRNA Source: MGI
  • regulation of mRNA stability Source: UniProtKB
  • regulation of neuronal action potential Source: UniProtKB
  • regulation of neurotransmitter secretion Source: UniProtKB
  • RNA splicing Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor, Ribonucleoprotein

Keywords - Biological processi

DNA damage, mRNA processing, mRNA splicing, mRNA transport, Neurogenesis, RNA-mediated gene silencing, Translation regulation, Transport

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptic functional regulator FMR1Curated
Alternative name(s):
Fragile X mental retardation protein 1 homologBy similarity
Short name:
FMRP1 Publication
Short name:
Protein FMR-11 Publication
Short name:
mFmr1p
Gene namesi
Name:Fmr1Imported
Synonyms:Fmr-11 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:95564. Fmr1.

Subcellular locationi

Isoform 4 :
  • Nucleus 1 Publication
  • Nucleusnucleoplasm 1 Publication

GO - Cellular componenti

  • axon Source: UniProtKB
  • axon terminus Source: UniProtKB
  • cell body Source: MGI
  • cell junction Source: UniProtKB-KW
  • cell projection Source: MGI
  • chromocenter Source: UniProtKB
  • chromosome Source: UniProtKB
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoplasmic ribonucleoprotein granule Source: UniProtKB
  • cytoplasmic stress granule Source: MGI
  • dendrite Source: UniProtKB
  • dendritic filopodium Source: UniProtKB
  • dendritic spine Source: UniProtKB
  • extrinsic component of plasma membrane Source: UniProtKB
  • filopodium tip Source: UniProtKB
  • glial cell projection Source: UniProtKB
  • growth cone Source: UniProtKB
  • growth cone filopodium Source: UniProtKB
  • intracellular ribonucleoprotein complex Source: MGI
  • membrane Source: MGI
  • mRNA cap binding complex Source: UniProtKB
  • neuronal ribonucleoprotein granule Source: UniProtKB
  • neuron projection Source: MGI
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: MGI
  • perikaryon Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • polysome Source: UniProtKB
  • postsynapse Source: UniProtKB
  • postsynaptic density Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-SubCell
  • presynapse Source: UniProtKB
  • presynaptic membrane Source: UniProtKB-SubCell
  • ribonucleoprotein complex Source: MGI
  • synapse Source: UniProtKB
  • viral replication complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Centromere, Chromosome, Cytoplasm, Membrane, Nucleus, Postsynaptic cell membrane, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

Show normal fertility (PubMed:8033209). Display enlarged testes and ovaries (PubMed:8033209, PubMed:23235829). Display learning deficits and hyperactivity, in the absence of gross pathological abnormalities of the brain (PubMed:8033209). Display immature neurons with excess of long, thin growth cone filopodia and dendritic filopodia and spine protrusions with less synaptic contacts (PubMed:9144249, PubMed:11438589, PubMed:16631377, PubMed:17417632, PubMed:18539120). Show no increase in the number of dendritic filopodia-spine protrusions in response to KCL-mediated depolarization (PubMed:16631377). Display alterations in the appearance, distribution and volume of nuclear speckles (PubMed:24349419). Display enhanced metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) in the hippocampus (PubMed:11438589, PubMed:16908410, PubMed:12032354). Leads to excessive presynaptic action potential (AP) broadening in hippocampal and cortical neurons (PubMed:25561520). Show alteration in the splicing pattern of its own FMR1 mRNA in the cortex (PubMed:18653529). Alters the abundance and subcellular distribution of a subset of mRNAs in the brain (PubMed:12575950, PubMed:17417632). Display a reduction in the recruitment of certain FMR1 target mRNAs in actively translating polyribosomes at synapses (PubMed:12575950, PubMed:17507556). Display decreased delivery of specific mRNAs into dendrites in mGluR-stimulated neurons (PubMed:18539120). Display a delayed MAPB1 protein expression decline in the developing hippocampus (PubMed:15475576). Show a relief of ribosome stalling on dendritic FMR1 target mRNAs (PubMed:21784246). Display enhanced postsynaptic protein synthesis of a subset of FMR1 target mRNAs (PubMed:12581522, PubMed:16908410, PubMed:19640847, PubMed:21784246). Unable to induce postsynaptic protein synthesis of a subset of FMR1 mRNA targets in response to mGluR activation (PubMed:16908410, PubMed:17507556). Display enhanced presynaptic protein synthesis of the voltage-dependent calcium channel CACNA1B (PubMed:24709664). Display also enhanced protein synthesis of a subset of FMR1 target mRNAs in ovaries (PubMed:23235829). Display reduced postsynaptic protein synthesis of a subset of FMR1 target mRNAs (PubMed:12927206, PubMed:14614133, PubMed:19640847, PubMed:19166269, PubMed:21490210). Display reduced general protein synthesis in synapses in response to mGluR activation (PubMed:15548614). Show brain-region specific reduction in the expression and/or localization of FAM206A/Simiate (PubMed:24349419). Display similar myelin basic protein (MBP) nexpression level in brain cerebrum than in wild-type mice (PubMed:23891804). Display an absence of nuclear foci on meiotic pachytene-stage chromosomes (PubMed:24813610). Show incomplete resolution of single-strand repair intermediates, crossing over and pairing of homologous chromosomes during meiotic prophase in a subset of spermatocytes (PubMed:24813610).26 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi429 – 434LRLERL → ARAERA: Inhibits nuclear export. 1 Publication6
Mutagenesisi429 – 431LRL → ARA: Inhibits nuclear export. 1 Publication3
Mutagenesisi499S → A: Loss of phosphorylation. 1 Publication1
Mutagenesisi499S → D: Leads to phosphorylation on other serine residues. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000501031 – 614Synaptic functional regulator FMR1Add BLAST614

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei336PhosphoserineBy similarity1
Modified residuei337PhosphoserineBy similarity1
Modified residuei349PhosphoserineBy similarity1
Modified residuei350PhosphoserineBy similarity1
Modified residuei369PhosphoserineBy similarity1
Modified residuei462PhosphothreonineCombined sources1
Modified residuei470Omega-N-methylarginineCombined sources1
Modified residuei499Phosphoserine1 Publication1
Modified residuei543Omega-N-methylarginine; alternateBy similarity1
Modified residuei543Omega-N-methylated arginine; alternateBy similarity1
Modified residuei602PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on several serine residues (PubMed:14570712). Phosphorylation at Ser-499 is required for phosphorylation of other nearby serine residues (PubMed:14570712). Phosphorylation has no effect on the binding of individual mRNA species, but may affect the association with polyribosome (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 snypases (PubMed:14570712).1 Publication
Monoubiquitinated (PubMed:16908410). Polyubiquitinated (PubMed:16908410). Ubiquitinated and targeted for proteasomal degradation after activation of metabotropic glutamate receptor (mGluR) (PubMed:16908410).1 Publication
Methylated; methylation is necessary for heterodimerization with FXR1, association with polyribosomes, recruitment into stress granules and translation of FMR1 target mRNAs. Methylated by PRMT1, PRMT3 and PRMT4, in vitro.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP35922.
PaxDbiP35922.
PeptideAtlasiP35922.
PRIDEiP35922.

PTM databases

iPTMnetiP35922.
PhosphoSitePlusiP35922.

Expressioni

Tissue specificityi

Expressed in brain (PubMed:8033209). Strongly expressed in the neonatal hippocampus (PubMed:15475576). Expressed in the brainstem (PubMed:14613971). Expressed in the cerebellum (PubMed:19193898). Expressed in neurons of hippocampal area CA3 (PubMed:17548835, PubMed:19193898). Expressed in neurons of the olfactory bulb including the granule, mitral, tufted and juxtaglomerular cells (PubMed:19193898). Expressed in both mature and immature olfactory sensory neurons (OSNs) (PubMed:19193898). Expressed in neurons in all layers and in all regions of cerebral cortex (PubMed:19193898). Expressed in mature oligodendrocytes (OLGs) (PubMed:23891804). Expressed in spermatogonia (at protein level) (PubMed:16790844). Expressed predominantly in the brain (PubMed:16000371). Expressed in testis (PubMed:8033209).8 Publications

Inductioni

Rapidly and transiently up-regulated in response to metabotropic glutamate receptor activation in a protein synthesis-dependent manner in neurons (at protein level).2 Publications

Gene expression databases

CleanExiMM_FMR1.

Interactioni

Subunit structurei

Homodimer (By similarity). Forms heterodimer with FXR1; heterodimerization occurs in a methylation-dependent manner (By similarity). Forms heterodimer with FXR2 (By similarity). Homooligomer (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex at least composed of CYFIP, EIF4E and FMR1; this mRNA cap binding complex formation increases in presence of the brain cytoplasmic RNA BC1 and is dynamically regulated in an activity-dependent manner to repress and then possibly release dendritic mRNAs for translation in response to mGluR stimulation (PubMed:18805096). Associates with the SMN core complex that contains SMN, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:18093976). Part of a ribonucleoprotein complex with AGO2/EIF2C2 and miRNAs (By similarity). Interacts with AGO2/EIF2C2 (By similarity). Interacts (via C-terminus) with CACNA1B; this interaction induces a deacrease in the number of presynaptic functional CACNA1B channels at the cell surface (PubMed:24709664). Interacts with CYFIP1; this interaction recruits CYFIP1 to capped mRNA (PubMed:11438699, PubMed:18805096). Interacts with CYFIP2 (PubMed:11438699). Interacts with EIF5; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with dynein (PubMed:18539120). Interacts with FXR1 and FXR2 (PubMed:10567518). Interacts with methylated histone H3 (By similarity). Interacts with IGF2BP1; this interaction allows to recruit IGF2BP1 to mRNA in a FMR1-dependent manner (By similarity). Interacts (via N-terminus) with KCNMB4 (PubMed:25561520). Interacts with KCNT1 (via C-terminus); this interaction alters gating properties of KCNT1 (PubMed:20512134). Interacts (via C-terminus) with KIF5A; this interaction is increased in a mGluR-dependent manner (PubMed:18539120). Interacts (via phosphorylated form) with MCRS1 (via N-terminus) (By similarity). Interacts with MOV10; this interaction is direct, occurs in an RNA-dependent manner on polysomes and induces association of MOV10 with RNAs (PubMed:25464849). Interacts with MYO5A and PURA; these interactions occur in association with polyribosome (PubMed:12147688). Interacts with NCL (PubMed:10567518). Interacts with NUFIP1 (PubMed:10556305). Interacts (via N-terminus) with NUFIP2 (By similarity). Interacts with NXF1; this interaction occurs in a mRNA-dependent and polyribosome-independent manner in the nucleus (By similarity). Interacts with NXF2 (via N-terminus); this interaction is direct and occurs in a NXF1 mRNA-containing mRNP complexes (PubMed:16790844, PubMed:17548835). Interacts with RANBP9; this interaction is direct and inhibits binding of FMR1 to RNA homopolymer (PubMed:15381419). Interacts with RPLP0 (PubMed:21784246). Interacts (via C-terminus) with SMN (via C-terminus); this interaction is direct and occurs in a RNA-independent manner (By similarity). Interacts with TDRD3 (via C-terminus); this interaction is direct (By similarity). Interacts with YBX1; this interaction occurs in association with polyribosome (PubMed:11162447). Interacts with nucleosome (By similarity). Associates with polyribosome; this association occurs in a mRNA-dependent manner (PubMed:8842725, PubMed:9285783, PubMed:12581522, PubMed:12575950, PubMed:14613971, PubMed:15317853, PubMed:15805463, PubMed:21784246). Associates with messenger ribonucleoprotein particles (mRNPs) (PubMed:8842725, PubMed:9285783, PubMed:11719188, PubMed:12581522, PubMed:12575950, PubMed:15329415, PubMed:18805096). Associates with microtubules in a kinesin- and dynein-dependent manner (PubMed:18539120).By similarity25 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rcan1Q9JHG63EBI-645094,EBI-644061

GO - Molecular functioni

Protein-protein interaction databases

IntActiP35922. 7 interactors.
MINTiMINT-111096.
STRINGi10090.ENSMUSP00000085906.

Structurei

3D structure databases

ProteinModelPortaliP35922.
SMRiP35922.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 50Agenet-like 1PROSITE-ProRule annotationAdd BLAST47
Domaini63 – 115Agenet-like 2PROSITE-ProRule annotationAdd BLAST53
Domaini222 – 251KH 1PROSITE-ProRule annotationAdd BLAST30
Domaini285 – 314KH 2PROSITE-ProRule annotationAdd BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 184Required for nuclear localization1 PublicationAdd BLAST184
Regioni172 – 211Necessary for interaction with CYFIP1, CYFIP2, FXR1 and FXR2By similarity1 PublicationAdd BLAST40
Regioni396 – 490Required for nuclear exportBy similarityAdd BLAST95
Regioni418 – 614Interaction with RANBP9By similarityAdd BLAST197
Regioni534 – 547RNA-binding RGG-boxAdd BLAST14

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi423 – 442Nuclear export signal1 PublicationAdd BLAST20
Motifi526 – 533Nucleolar localization signal 1By similarity8
Motifi595 – 599Nucleolar localization signal 2By similarity5

Domaini

The N-terminal 134 amino acids are necessary for homodimerization and RNA-binding. The N-terminal 298 amino acids are sufficient to interact with KCNMB4 and to regulate presynaptic action potential (AP) duration in neurons. The two agenet-like domains are necessary for binding to histone H3 in a methylation-dependent manner. The KH domains are necessary for mediating miRNA annealing to specific RNA targets. The KH 2 domain is necessary for binding to kissing complex (kc) RNA ligands. The RGG box domain is necessary for binding to mRNA targets that contain G-quadruplex structures. The RGG-box domain is necessary for binding to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the superoxide dismutase SOD1 mRNA. The RGG box domain is necessary for binding to its own mRNA. The RGG-box domain is necessary for binding to homopolymer poly(G).By similarity

Sequence similaritiesi

Belongs to the FMR1 family.Curated
Contains 2 Agenet-like domains.PROSITE-ProRule annotation
Contains 2 KH domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IF9J. Eukaryota.
ENOG410ZDJG. LUCA.
HOGENOMiHOG000293377.
HOVERGENiHBG005739.
InParanoidiP35922.
PhylomeDBiP35922.

Family and domain databases

Gene3Di3.30.1370.10. 3 hits.
InterProiIPR008395. Agenet-like_dom.
IPR032196. FXMR_C2.
IPR022034. FXMRP1_C_core.
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
[Graphical view]
PfamiPF05641. Agenet. 1 hit.
PF16098. FXMR_C2. 2 hits.
PF12235. FXMRP1_C_core. 1 hit.
PF00013. KH_1. 2 hits.
[Graphical view]
SMARTiSM00322. KH. 2 hits.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 2 hits.
PROSITEiPS51641. AGENET_LIKE. 2 hits.
PS50084. KH_TYPE_1. 2 hits.
[Graphical view]

Sequences (12)i

Sequence statusi: Complete.

This entry describes 12 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35922-1) [UniParc]FASTAAdd to basket
Also known as: ISO1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEELVVEVRG SNGAFYKAFV KDVHEDSITV AFENNWQPER QIPFHDVRFP
60 70 80 90 100
PPVGYNKDIN ESDEVEVYSR ANEKEPCCWW LAKVRMIKGE FYVIEYAACD
110 120 130 140 150
ATYNEIVTIE RLRSVNPNKP ATKDTFHKIK LEVPEDLRQM CAKESAHKDF
160 170 180 190 200
KKAVGAFSVT YDPENYQLVI LSINEVTSKR AHMLIDMHFR SLRTKLSLIL
210 220 230 240 250
RNEEASKQLE SSRQLASRFH EQFIVREDLM GLAIGTHGAN IQQARKVPGV
260 270 280 290 300
TAIDLDEDTC TFHIYGEDQD AVKKARSFLE FAEDVIQVPR NLVGKVIGKN
310 320 330 340 350
GKLIQEIVDK SGVVRVRIEA ENEKSVPQEE EIMPPSSLPS NNSRVGPNSS
360 370 380 390 400
EEKKHLDTKE NTHFSQPNST KVQRVLVVSS IVAGGPQKPE PKAWQGMVPF
410 420 430 440 450
VFVGTKDSIA NATVLLDYHL NYLKEVDQLR LERLQIDEQL RQIGASSRPP
460 470 480 490 500
PNRTDKEKGY VTDDGQGMGR GSRPYRNRGH GRRGPGYTSG TNSEASNASE
510 520 530 540 550
TESDHRDELS DWSLAPTEEE RESFLRRGDG RRRRGGGRGQ GGRGRGGGFK
560 570 580 590 600
GNDDHSRTDN RPRNPREAKG RTADGSLQSA SSEGSRLRTG KDRNQKKEKP
610
DSVDGLQPLV NGVP
Length:614
Mass (Da):68,989
Last modified:June 1, 1994 - v1
Checksum:i093DD90D589ED066
GO
Isoform 2 (identifier: P35922-2) [UniParc]FASTAAdd to basket
Also known as: ISO2

The sequence of this isoform differs from the canonical sequence as follows:
     490-501: Missing.

Show »
Length:602
Mass (Da):67,840
Checksum:i731A506F0359F0E5
GO
Isoform 3 (identifier: P35922-3) [UniParc]FASTAAdd to basket
Also known as: ISO3

The sequence of this isoform differs from the canonical sequence as follows:
     490-514: Missing.

Show »
Length:589
Mass (Da):66,269
Checksum:i9462AD5A666E906A
GO
Isoform 4 (identifier: P35922-4) [UniParc]FASTAAdd to basket
Also known as: ISO4

The sequence of this isoform differs from the canonical sequence as follows:
     425-448: EVDQLRLERLQIDEQLRQIGASSR → ELILKHQMLLKQNLTTETNSVIGH
     449-614: Missing.

Show »
Length:448
Mass (Da):50,829
Checksum:i0F25006E964AD90C
GO
Isoform 5 (identifier: P35922-5) [UniParc]FASTAAdd to basket
Also known as: ISO5

The sequence of this isoform differs from the canonical sequence as follows:
     425-436: EVDQLRLERLQI → NLTTETNSVIGH
     437-614: Missing.

Show »
Length:436
Mass (Da):49,353
Checksum:i5AB0A796CC0CF180
GO
Isoform 6 (identifier: P35922-6) [UniParc]FASTAAdd to basket
Also known as: ISO6

The sequence of this isoform differs from the canonical sequence as follows:
     425-512: EVDQLRLERL...SDHRDELSDW → LQQRKRGRAS...VTRRRKSQTA
     513-614: Missing.

Show »
Length:512
Mass (Da):58,113
Checksum:i093A5C6493C61131
GO
Isoform 7 (identifier: P35922-7) [UniParc]FASTAAdd to basket
Also known as: ISO7

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.

Show »
Length:593
Mass (Da):66,817
Checksum:iA5775ADA3613D93D
GO
Isoform 8 (identifier: P35922-8) [UniParc]FASTAAdd to basket
Also known as: ISO8

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.
     490-501: Missing.

Show »
Length:581
Mass (Da):65,667
Checksum:i64ED438071325D40
GO
Isoform 9 (identifier: P35922-9) [UniParc]FASTAAdd to basket
Also known as: ISO9

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.
     490-514: Missing.

Show »
Length:568
Mass (Da):64,097
Checksum:i94B1FEC72A1C7D1D
GO
Isoform 10 (identifier: P35922-10) [UniParc]FASTAAdd to basket
Also known as: ISO10

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.
     425-448: EVDQLRLERLQIDEQLRQIGASSR → ELILKHQMLLKQNLTTETNSVIGH
     449-614: Missing.

Show »
Length:427
Mass (Da):48,656
Checksum:i8F1236A4CBBAE6FA
GO
Isoform 11 (identifier: P35922-11) [UniParc]FASTAAdd to basket
Also known as: ISO11

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.
     425-436: EVDQLRLERLQI → NLTTETNSVIGH
     437-614: Missing.

Show »
Length:415
Mass (Da):47,180
Checksum:i8F5306E3316AAFF1
GO
Isoform 12 (identifier: P35922-12) [UniParc]FASTAAdd to basket
Also known as: ISO12

The sequence of this isoform differs from the canonical sequence as follows:
     375-395: Missing.
     425-512: EVDQLRLERL...SDHRDELSDW → LQQRKRGRAS...VTRRRKSQTA
     513-614: Missing.

Show »
Length:491
Mass (Da):55,940
Checksum:iF16075B4136A226F
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002827375 – 395Missing in isoform 7, isoform 8, isoform 9, isoform 10, isoform 11 and isoform 12. CuratedAdd BLAST21
Alternative sequenceiVSP_002834425 – 512EVDQL…ELSDW → LQQRKRGRASCAEETDGGVE EEEEDKEEEEEEEASKETTI IPEQIIVHVIQERLKEEQLM DPCRVPPVKGAGCARVKIVT RRRKSQTA in isoform 6 and isoform 12. CuratedAdd BLAST88
Alternative sequenceiVSP_002831425 – 448EVDQL…GASSR → ELILKHQMLLKQNLTTETNS VIGH in isoform 4 and isoform 10. CuratedAdd BLAST24
Alternative sequenceiVSP_002832425 – 436EVDQL…ERLQI → NLTTETNSVIGH in isoform 5 and isoform 11. CuratedAdd BLAST12
Alternative sequenceiVSP_002833437 – 614Missing in isoform 5 and isoform 11. CuratedAdd BLAST178
Alternative sequenceiVSP_002830449 – 614Missing in isoform 4 and isoform 10. CuratedAdd BLAST166
Alternative sequenceiVSP_002829490 – 514Missing in isoform 3 and isoform 9. CuratedAdd BLAST25
Alternative sequenceiVSP_002828490 – 501Missing in isoform 2 and isoform 8. CuratedAdd BLAST12
Alternative sequenceiVSP_002835513 – 614Missing in isoform 6 and isoform 12. CuratedAdd BLAST102

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L23971 mRNA. Translation: AAA37635.1.
CCDSiCCDS30171.1. [P35922-1]
CCDS72385.1. [P35922-3]
PIRiS36173.
UniGeneiMm.3451.

Genome annotation databases

UCSCiuc009tiu.2. mouse. [P35922-1]
uc009tiv.2. mouse. [P35922-11]
uc009tiy.1. mouse. [P35922-5]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L23971 mRNA. Translation: AAA37635.1.
CCDSiCCDS30171.1. [P35922-1]
CCDS72385.1. [P35922-3]
PIRiS36173.
UniGeneiMm.3451.

3D structure databases

ProteinModelPortaliP35922.
SMRiP35922.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP35922. 7 interactors.
MINTiMINT-111096.
STRINGi10090.ENSMUSP00000085906.

PTM databases

iPTMnetiP35922.
PhosphoSitePlusiP35922.

Proteomic databases

MaxQBiP35922.
PaxDbiP35922.
PeptideAtlasiP35922.
PRIDEiP35922.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiuc009tiu.2. mouse. [P35922-1]
uc009tiv.2. mouse. [P35922-11]
uc009tiy.1. mouse. [P35922-5]

Organism-specific databases

MGIiMGI:95564. Fmr1.

Phylogenomic databases

eggNOGiENOG410IF9J. Eukaryota.
ENOG410ZDJG. LUCA.
HOGENOMiHOG000293377.
HOVERGENiHBG005739.
InParanoidiP35922.
PhylomeDBiP35922.

Miscellaneous databases

ChiTaRSiFmr1. mouse.
PROiP35922.
SOURCEiSearch...

Gene expression databases

CleanExiMM_FMR1.

Family and domain databases

Gene3Di3.30.1370.10. 3 hits.
InterProiIPR008395. Agenet-like_dom.
IPR032196. FXMR_C2.
IPR022034. FXMRP1_C_core.
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
[Graphical view]
PfamiPF05641. Agenet. 1 hit.
PF16098. FXMR_C2. 2 hits.
PF12235. FXMRP1_C_core. 1 hit.
PF00013. KH_1. 2 hits.
[Graphical view]
SMARTiSM00322. KH. 2 hits.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 2 hits.
PROSITEiPS51641. AGENET_LIKE. 2 hits.
PS50084. KH_TYPE_1. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFMR1_MOUSE
AccessioniPrimary (citable) accession number: P35922
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.