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UniProtKB - Q06787 (FMR1_HUMAN)

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Protein

Synaptic functional regulator FMR1

Gene

FMR1

Organism
Homo sapiens (Human)
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:16631377, PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Plays a role in mRNA nuclear export (By similarity). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (By similarity). 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 (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 (By similarity). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postnyaptic dendritic spines (PubMed:11532944, PubMed:11157796, PubMed:12594214, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (By similarity). Represses mRNA translation by stalling ribosomal translocation during elongation (By similarity). Reports are contradictory with regards to its ability to mediate translation inhibition of MBP mRNA in oligodendrocytes (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:14703574, PubMed:17057366, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (PubMed:17057366). Plays also a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:19097999, PubMed:19166269). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (By similarity). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:7692601, PubMed:11719189, PubMed:11157796, PubMed:12594214, PubMed:17417632, PubMed:23235829, PubMed:24448548). 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 (PubMed:23235829). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:11719189, PubMed:18579868, PubMed:25464849, PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (PubMed:7692601, PubMed:11532944, PubMed:12594214, PubMed:15282548, PubMed:18653529). Binds also to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (PubMed:15805463). Binds mRNAs containing U-rich target sequences (PubMed:12927206). 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 (By similarity). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (By similarity). Binds to a subset of miRNAs in the brain (PubMed:14703574, PubMed:17057366). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (PubMed:18936162). 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) (PubMed:7688265, PubMed:7781595, PubMed:12950170, PubMed:15381419, PubMed:8156595). 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 (By similarity). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (By similarity). 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 similarity30 Publications
Isoform 10: binds to RNA homopolymer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304).1 Publication
Isoform 6: binds to RNA homopolymer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304).1 Publication
(Microbial infection) Acts as a positive regulator of influenza A virus (IAV) replication. Required for the assembly and nuclear export of the viral ribonucleoprotein (vRNP) components.1 Publication

Miscellaneous

The mechanism of the severe phenotype in the Asn-304 patient lies in the sequestration of bound mRNAs in nontranslatable mRNP particles. In the absence of FMRP, these same mRNAs may be partially translated via alternate mRNPs, although perhaps abnormally localized or regulated, resulting in typical fragile X syndrome. Asn-304 mutation maps to a position within the second KH domain of FMRP that is critical for stabilizing sequence-specific RNA-protein interactions. Asn-304 mutation abrogates the association of the FMRP KH 2 domain with its target, kissing complex RNA.

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • dynein complex binding Source: UniProtKB
  • G-quadruplex RNA binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • ion channel binding Source: UniProtKB
  • 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(G) binding Source: UniProtKB
  • poly(U) RNA binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ribosome binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • 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: UniProtKB
  • translation repressor activity Source: UniProtKB
Complete GO annotation...

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: UniProtKB
  • gene silencing by RNA Source: UniProtKB-KW
  • glutamate receptor signaling pathway Source: UniProtKB
  • modulation by host of viral RNA genome replication Source: UniProtKB
  • mRNA processing Source: UniProtKB-KW
  • mRNA transport Source: UniProtKB
  • negative regulation of cytoplasmic translation Source: UniProtKB
  • negative regulation of long term synaptic depression Source: UniProtKB
  • negative regulation of mRNA catabolic process Source: CAFA
  • negative regulation of synaptic vesicle exocytosis 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: UniProtKB
  • 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: UniProtKB
  • regulation of mRNA stability Source: UniProtKB
  • regulation of neuronal action potential Source: UniProtKB
  • regulation of neurotransmitter secretion Source: UniProtKB
  • RNA splicing Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywordsi

Molecular functionActivator, Repressor, Ribonucleoprotein, RNA-binding
Biological processDNA damage, Host-virus interaction, mRNA processing, mRNA splicing, mRNA transport, Neurogenesis, RNA-mediated gene silencing, Translation regulation, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptic functional regulator FMR1Curated
Alternative name(s):
Fragile X mental retardation protein 1Imported
Short name:
FMRP1 Publication
Short name:
Protein FMR-11 Publication
Gene namesi
Name:FMR1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:3775. FMR1.

Subcellular locationi

Isoform 6 :
Isoform 9 :
Isoform 10 :
  • Nucleus 1 Publication
  • Nucleus › Cajal body 1 Publication

    • Note: Colocalizes with Colin and SMN in Cajal bodies (PubMed:24204304).
Isoform 11 :
  • Nucleus 1 Publication
  • Nucleus › Cajal body 1 Publication

GO - Cellular componenti

  • axon Source: UniProtKB
  • axon terminus Source: UniProtKB
  • Cajal body Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • cell projection Source: UniProtKB
  • chromocenter Source: UniProtKB
  • chromosome Source: UniProtKB
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoplasmic ribonucleoprotein granule Source: UniProtKB
  • cytosol Source: HPA
  • 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: UniProtKB
  • membrane Source: UniProtKB
  • messenger ribonucleoprotein complex Source: CAFA
  • mRNA cap binding complex Source: UniProtKB
  • neuronal ribonucleoprotein granule Source: UniProtKB
  • neuron projection Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • 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: UniProtKB
  • synapse Source: UniProtKB
  • viral replication complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Fragile X syndrome (FRAX)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCommon genetic disease (has a prevalence of one in every 2000 children) which is characterized by moderate to severe mental retardation, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most fragile X syndrome patients results from an amplification of a CGG repeat region which is directly in front of the coding region.
See also OMIM:300624
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064507138R → Q in FRAX; rare variant found in a developmentally delayed male; inhibits nucleosome binding; reduces interaction with KCNMB4; inhibits presynaptic action potential (AP) broadening; does not alter postsynaptic RNA-binding and polyribosome association. 3 PublicationsCorresponds to variant dbSNP:rs200163413Ensembl.1
Natural variantiVAR_075977266G → E in FRAX; reduces association with polyribosome; reduces RNA-binding. 1 Publication1
Natural variantiVAR_005234304I → N in FRAX; alters protein folding and stability; increases nucleocytoplasmic shuttling; reduces localization in Cajal bodies; reduces the association with cytoplasmic granules; reduces association with polyribosome; reduces RNA-binding; attenuates mRNA translation repression; impairs homooligomerization; reduces interaction with TDRD3; reduces interaction with viral influenza A nucleoprotein (NP); does not inhibit interaction with SMN1, FXR1 and FXR2. 14 PublicationsCorresponds to variant dbSNP:rs121434622Ensembl.1
Fragile X tremor/ataxia syndrome (FXTAS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionIn FXTAS, the expanded repeats range in size from 55 to 200 repeats and are referred to as 'premutations'. Full repeat expansions with greater than 200 repeats results in fragile X mental retardation syndrome [MIM:300624]. Carriers of the premutation typically do not show the full fragile X syndrome phenotype, but comprise a subgroup that may have some physical features of fragile X syndrome or mild cognitive and emotional problems.
See also OMIM:300623
Premature ovarian failure 1 (POF1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
See also OMIM:311360

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi102T → A: Reduces binding to nucleosome. 1 Publication1
Mutagenesisi103Y → L: Reduces binding to nucleosome. 1 Publication1
Mutagenesisi125 – 126TF → AA: Alters the structural integrity of the N-terminus and leads to aggregation. 1 Publication2
Mutagenesisi500S → A: Loss of phosphorylation. Does not affect interaction with MCRS1. Does not affect localization to cytoplasmic granules. Does not affect association with polyribosome. 3 Publications1
Mutagenesisi500S → D: Does not affect RNA-binding to G-quadruplex structure. 1 Publication1
Mutagenesisi527 – 534RRGDGRRR → EEGDGEEE: Reduces nucleolar localization. Strongly reduces nucleolar localization; when associated with 613-E--E-617. 1 Publication8
Mutagenesisi544R → K: Reduces arginine methylation by 80%. 1 Publication1
Mutagenesisi546R → K: Slightly reduced methylation. 1 Publication1
Mutagenesisi613 – 617QKKEK → EEEEE: Reduces nucleolar localization. Strongly reduces nucleolar localization; when associated with 527-E--E-534. 1 Publication5

Keywords - Diseasei

Disease mutation, Mental retardation, Premature ovarian failure

Organism-specific databases

DisGeNETi2332.
GeneReviewsiFMR1.
MalaCardsiFMR1.
MIMi300623. phenotype.
300624. phenotype.
311360. phenotype.
616034. phenotype.
OpenTargetsiENSG00000102081.
Orphaneti908. Fragile X syndrome.
93256. Fragile X-associated tremor/ataxia syndrome.
619. Primary ovarian failure.
261483. Xq27.3q28 duplication syndrome.
PharmGKBiPA28191.

Polymorphism and mutation databases

BioMutaiFMR1.
DMDMi544328.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000501021 – 632Synaptic functional regulator FMR1Add BLAST632

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei337PhosphoserineBy similarity1
Modified residuei370PhosphoserineCombined sources1
Modified residuei463PhosphothreonineBy similarity1
Modified residuei471Omega-N-methylarginineBy similarity1
Modified residuei500PhosphoserineCombined sources1 Publication1
Modified residuei544Omega-N-methylarginine1 Publication1
Modified residuei620PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated (PubMed:14532325). Phosphorylated on several serine residues. Phosphorylation at Ser-500 is required for phosphorylation of other nearby serine residues. Phosphorylation has no effect on the binding of individual mRNA species, but may affect the association with polyribosome. Unphosphorylated FMR1 is associated with actively translating polyribosome, whereas a fraction of phosphorylated FMR1 is associated with apparently stalled polyribosome. Dephosphorylation by an activated phosphatase may release the FMR1-mediated translational repression and allow synthesis of a locally required protein at snypases (By similarity).By similarity1 Publication
Monoubiquitinated. Polyubiquitinated. Ubiquitinated and targeted for proteasomal degradation after activation of metabotropic glutamate receptor (mGluR).By similarity
Methylated; methylation is necessary for heterodimerization with FXR1, association with polyribosomes, recruitment into stress granules and translation of FMR1 target mRNAs (PubMed:16636078). Methylated by PRMT1, PRMT3 and PRMT4, in vitro (PubMed:16922515).2 Publications
Isoform 10: Undergoes proteolytic cleavage; may be specifically cleaved by calpain-1/CAPN1 in cajal bodies (PubMed:24204304).1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ06787.
MaxQBiQ06787.
PaxDbiQ06787.
PeptideAtlasiQ06787.
PRIDEiQ06787.

PTM databases

iPTMnetiQ06787.
PhosphoSitePlusiQ06787.

Expressioni

Tissue specificityi

Expressed in the brain, cerebellum and testis (PubMed:8401578). Also expressed in epithelial tissues (PubMed:8401578). Expressed in mature oligodendrocytes (OLGs) (PubMed:23891804). Expressed in fibroblast (PubMed:24204304). Expressed in neurons, Purkinje cells and spermatogonias (at protein level) (PubMed:8401578). Expressed in brain, testis and placenta (PubMed:8504300). Expressed in neurons and lymphocytes (PubMed:8504300).4 Publications

Inductioni

(Microbial infection) Up-regulated in response to infection by influenza A virus.1 Publication

Gene expression databases

BgeeiENSG00000102081.
CleanExiHS_FMR1.
ExpressionAtlasiQ06787. baseline and differential.
GenevisibleiQ06787. HS.

Organism-specific databases

HPAiCAB012444.
HPA050118.
HPA056084.

Interactioni

Subunit structurei

Homodimer (PubMed:7489725, PubMed:12950170, PubMed:16636078). Forms heterodimer with FXR1; heterodimerization occurs in a methylation-dependent manner (PubMed:7489725, PubMed:11157796, PubMed:16636078). Forms heterodimer with FXR2 (PubMed:7489725, PubMed:11157796). Homooligomer (PubMed:11157796, PubMed:18664458). 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 (By similarity). 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 (PubMed:14703574). Interacts with AGO2/EIF2C2 (PubMed:14703574). Interacts (via C-terminus) with CACNA1B; this interaction induces a deacrease in the number of presynaptic functional CACNA1B channels at the cell surface (By similarity). Interacts with CYFIP1; this interaction recruits CYFIP1 to capped mRNA (By similarity). Interacts with CYFIP2 (By similarity). Interacts with EIF5; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with dynein (By similarity). Interacts with FXR1 and FXR2 (PubMed:8668200, PubMed:14532325, PubMed:15380484). Interacts with methylated histone H3 (PubMed:24813610). Interacts with IGF2BP1; this interaction allows to recruit IGF2BP1 to mRNA in a FMR1-dependent manner (PubMed:15282548). 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 phosphorylated form) with MCRS1 (via N-terminus) (PubMed:16571602). 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 (By similarity). Interacts with NCL (By similarity). Interacts with NUFIP1 (PubMed:10556305). Interacts (via N-terminus) with NUFIP2 (PubMed:12837692, PubMed:16407062). Interacts with NXF1; this interaction occurs in a mRNA-dependent and polyribosome-independent manner in the nucleus (PubMed:18936162). Interacts with NXF2 (via N-terminus); this interaction is direct and occurs in a NXF1 mRNA-containing mRNP complexes (By similarity). Interacts with RANBP9 (via C-terminus); this interaction is direct and inhibits binding of FMR1 to RNA homopolymer (PubMed:15381419). Interacts with RPLP0 (PubMed:15380484). Interacts (via C-terminus) with SMN (via C-terminus); this interaction is direct and occurs in a RNA-independent manner (PubMed:18093976). Interacts with TDRD3 (via C-terminus); this interaction is direct (PubMed:18632687, PubMed:18664458). Interacts with YBX1; this interaction occurs in association with polyribosome (By similarity). Interacts with nucleosome (PubMed:24813610). Associates with polyribosome; this association occurs in a mRNA-dependent manner (PubMed:9659908, PubMed:11719188, PubMed:12594214, PubMed:19097999, PubMed:24448548). Associates with cytoplasmic messenger ribonucleoprotein particles (mRNPs) (PubMed:7692601, PubMed:9659908, PubMed:12575950, PubMed:19097999). Associates with microtubules in a kinesin- and dynein-dependent manner (By similarity). Isoform 6 interacts (via N-terminus) with NCL (via C-terminus) (PubMed:24658146). Isoform 6 interacts with CYFIP2; this interaction occurs in a RNA-dependent manner (PubMed:24658146). Isoform 6 interacts with EIF5; this interaction occurs in a RNA-dependent manner (PubMed:24658146). Isoform 6 interacts with RPLP0 (PubMed:24658146).By similarity30 Publications
(Microbial infection) Interacts (via KH 2 domain) with influenza A nucleoprotein (NP); this interaction occurs in a RNA-dependent manner and stimulates viral ribonucleoprotein (vRNP) assembly and subsequent RNA synthesis.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • dynein complex binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • ion channel binding Source: UniProtKB
  • methylated histone binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • translation initiation factor binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi108619. 59 interactors.
DIPiDIP-29022N.
DIP-29509N.
IntActiQ06787. 42 interactors.
MINTiMINT-108156.
STRINGi9606.ENSP00000359506.

Structurei

Secondary structure

1632
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 9Combined sources5
Beta strandi15 – 23Combined sources9
Beta strandi25 – 32Combined sources8
Helixi33 – 35Combined sources3
Beta strandi40 – 43Combined sources4
Helixi44 – 46Combined sources3
Beta strandi64 – 69Combined sources6
Beta strandi71 – 75Combined sources5
Beta strandi78 – 88Combined sources11
Beta strandi91 – 97Combined sources7
Helixi100 – 103Combined sources4
Beta strandi104 – 108Combined sources5
Helixi109 – 111Combined sources3
Beta strandi112 – 114Combined sources3
Turni123 – 125Combined sources3
Beta strandi127 – 132Combined sources6
Turni135 – 138Combined sources4
Helixi139 – 141Combined sources3
Helixi144 – 147Combined sources4
Helixi148 – 154Combined sources7
Beta strandi157 – 162Combined sources6
Turni163 – 166Combined sources4
Beta strandi167 – 173Combined sources7
Helixi177 – 198Combined sources22
Beta strandi220 – 224Combined sources5
Helixi227 – 229Combined sources3
Helixi230 – 234Combined sources5
Helixi236 – 238Combined sources3
Helixi239 – 245Combined sources7
Beta strandi250 – 256Combined sources7
Turni257 – 260Combined sources4
Beta strandi261 – 268Combined sources8
Helixi269 – 279Combined sources11
Beta strandi281 – 289Combined sources9
Helixi290 – 292Combined sources3
Helixi293 – 297Combined sources5
Helixi299 – 301Combined sources3
Helixi302 – 311Combined sources10
Beta strandi314 – 321Combined sources8
Beta strandi398 – 406Combined sources9
Helixi407 – 422Combined sources16
Beta strandi535 – 538Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BKDNMR-N1-134[»]
2FMRNMR-A216-280[»]
2LA5NMR-B527-541[»]
2QNDX-ray1.90A/B216-425[»]
4OVAX-ray3.00A/B/C/D1-209[»]
4QVZX-ray3.20A/B1-213[»]
4QW2X-ray2.99A/B1-213[»]
5DE5X-ray3.00B/D528-544[»]
5DE8X-ray3.10B/D528-544[»]
5DEAX-ray2.80B/D528-544[»]
5UWJX-ray2.22D423-437[»]
5UWOX-ray2.35D422-438[»]
DisProtiDP00134.
ProteinModelPortaliQ06787.
SMRiQ06787.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06787.

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 localizationBy similarityAdd BLAST184
Regioni172 – 211Necessary for interaction with CYFIP1, CYFIP2, FXR1 and FXR2By similarity2 PublicationsAdd BLAST40
Regioni397 – 491Required for nuclear export2 PublicationsAdd BLAST95
Regioni419 – 632Interaction with RANBP91 PublicationAdd BLAST214
Regioni534 – 548RNA-binding RGG-boxAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi424 – 443Nuclear export signalBy similarityAdd BLAST20
Motifi527 – 534Nucleolar localization signal 11 Publication8
Motifi613 – 617Nucleolar localization signal 21 Publication5

Domaini

The N-terminal 134 amino acids are necessary for homodimerization and RNA-binding (PubMed:12950170). The N-terminal 298 amino acids are sufficient to interact with KCNMB4 and to regulate presynaptic action potential (AP) duration in neurons (PubMed:25561520). The two agenet-like domains are necessary for binding to histone H3 in a methylation-dependent manner (PubMed:24813610). The KH domains are necessary for mediating miRNA annealing to specific RNA targets (PubMed:17057366). The KH 2 domain is necessary for binding to kissing complex (kc) RNA ligands (PubMed:15805463). The RGG box domain is necessary for binding to mRNA targets that contain G-quadruplex structures (PubMed:11719189, PubMed:18579868, PubMed:25692235). 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 (PubMed:19166269). The RGG box domain is necessary for binding to its own mRNA (PubMed:11532944). The RGG-box domain is necessary for binding to homopolymer poly(G) (PubMed:14532325).11 Publications
Isoform 10: The C-terminal region contains a Cajal body localization signal at positions 490 through 506 (PubMed:24204304).1 Publication

Sequence similaritiesi

Belongs to the FMR1 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IF9J. Eukaryota.
ENOG410ZDJG. LUCA.
GeneTreeiENSGT00390000017033.
HOVERGENiHBG005739.
InParanoidiQ06787.
KOiK15516.
OMAiRETCGWW.
OrthoDBiEOG091G08EZ.
PhylomeDBiQ06787.
TreeFamiTF105427.

Family and domain databases

Gene3Di3.30.1370.10. 2 hits.
InterProiView protein in InterPro
IPR008395. Agenet-like_dom.
IPR032196. FXMR_C2.
IPR022034. FXMRP1_C_core.
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
PfamiView protein in Pfam
PF05641. Agenet. 1 hit.
PF16098. FXMR_C2. 1 hit.
PF12235. FXMRP1_C_core. 1 hit.
PF00013. KH_1. 2 hits.
SMARTiView protein in SMART
SM00322. KH. 2 hits.
SUPFAMiSSF54791. SSF54791. 2 hits.
PROSITEiView protein in PROSITE
PS51641. AGENET_LIKE. 2 hits.
PS50084. KH_TYPE_1. 2 hits.

Sequences (11)i

Sequence statusi: Complete.

This entry describes 11 isoformsi produced by alternative splicing. AlignAdd to basket

Note: At least 12 different isoforms are produced.
Isoform 6 (identifier: Q06787-1) [UniParc]FASTAAdd to basket

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 AFENNWQPDR QIPFHDVRFP 
        60         70         80         90        100
PPVGYNKDIN ESDEVEVYSR ANEKEPCCWW LAKVRMIKGE FYVIEYAACD 
       110        120        130        140        150
ATYNEIVTIE RLRSVNPNKP ATKDTFHKIK LDVPEDLRQM CAKEAAHKDF 
       160        170        180        190        200
KKAVGAFSVT YDPENYQLVI LSINEVTSKR AHMLIDMHFR SLRTKLSLIM 
       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 ENEKNVPQEE EIMPPNSLPS NNSRVGPNAP 
       360        370        380        390        400
EEKKHLDIKE NSTHFSQPNS TKVQRVLVAS SVVAGESQKP ELKAWQGMVP 
       410        420        430        440        450
FVFVGTKDSI ANATVLLDYH LNYLKEVDQL RLERLQIDEQ LRQIGASSRP 
       460        470        480        490        500
PPNRTDKEKS YVTDDGQGMG RGSRPYRNRG HGRRGPGYTS GTNSEASNAS 
       510        520        530        540        550
ETESDHRDEL SDWSLAPTEE ERESFLRRGD GRRRGGGGRG QGGRGRGGGF 
       560        570        580        590        600
KGNDDHSRTD NRPRNPREAK GRTTDGSLQI RVDCNNERSV HTKTLQNTSS 
       610        620        630 
EGSRLRTGKD RNQKKEKPDS VDGQQPLVNG VP
Length:632
Mass (Da):71,174
Last modified:June 1, 1994 - v1
Checksum:iF853D6C82E3489B9
GO
Isoform 1 (identifier: Q06787-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     376-396: Missing.
     580-596: Missing.

Show »
Length:594
Mass (Da):66,971
Checksum:iBC65C14768EB268C
GO
Isoform 2 (identifier: Q06787-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-502: Missing.

Show »
Length:620
Mass (Da):70,025
Checksum:i8C8BC3876E1D92CA
GO
Isoform 3 (identifier: Q06787-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-502: Missing.
     580-596: Missing.

Show »
Length:603
Mass (Da):68,030
Checksum:iB8F3364E88A3489B
GO
Isoform 4 (identifier: Q06787-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-515: Missing.

Show »
Length:607
Mass (Da):68,455
Checksum:i561113CBB00CCAD0
GO
Isoform 5 (identifier: Q06787-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-515: Missing.
     580-596: Missing.

Show »
Length:590
Mass (Da):66,460
Checksum:i643FA1A3826879A3
GO
Isoform 7 (identifier: Q06787-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     580-596: Missing.

Show »
Length:615
Mass (Da):69,179
Checksum:iFE061178DA0A7ABB
GO
Isoform 8 (identifier: Q06787-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     376-396: Missing.
     491-515: Missing.

Show »
Length:586
Mass (Da):66,246
Checksum:iB413D4F8FA0D697F
GO
Isoform 9 (identifier: Q06787-9) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     376-396: Missing.

Show »
Length:611
Mass (Da):68,966
Checksum:iE69936008EABA9D6
GO
Isoform 10 (identifier: Q06787-10) [UniParc]FASTAAdd to basket
Also known as: ISO61 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     426-632: EVDQLRLERL...GQQPLVNGVP → LQQRKRGRAS...QTAWMVSNHS

Show »
Length:537
Mass (Da):61,043
Checksum:i5E1324A8B0C34C26
GO
Isoform 11 (identifier: Q06787-11) [UniParc]FASTAAdd to basket
Also known as: ISO121 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     376-396: Missing.
     426-632: EVDQLRLERL...GQQPLVNGVP → LQQRKRGRAS...QTAWMVSNHS

Show »
Length:516
Mass (Da):58,835
Checksum:i3E95B836A3811D3C
GO

Sequence cautioni

The sequence AAA52458 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAA62466 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAA62467 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti294 – 295Missing in AAA52458 (PubMed:1710175).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064507138R → Q in FRAX; rare variant found in a developmentally delayed male; inhibits nucleosome binding; reduces interaction with KCNMB4; inhibits presynaptic action potential (AP) broadening; does not alter postsynaptic RNA-binding and polyribosome association. 3 PublicationsCorresponds to variant dbSNP:rs200163413Ensembl.1
Natural variantiVAR_029278145A → S. Corresponds to variant dbSNP:rs29281Ensembl.1
Natural variantiVAR_075977266G → E in FRAX; reduces association with polyribosome; reduces RNA-binding. 1 Publication1
Natural variantiVAR_005234304I → N in FRAX; alters protein folding and stability; increases nucleocytoplasmic shuttling; reduces localization in Cajal bodies; reduces the association with cytoplasmic granules; reduces association with polyribosome; reduces RNA-binding; attenuates mRNA translation repression; impairs homooligomerization; reduces interaction with TDRD3; reduces interaction with viral influenza A nucleoprotein (NP); does not inhibit interaction with SMN1, FXR1 and FXR2. 14 PublicationsCorresponds to variant dbSNP:rs121434622Ensembl.1
Natural variantiVAR_005235546R → H1 PublicationCorresponds to variant dbSNP:rs782651077Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002823376 – 396Missing in isoform 1, isoform 8, isoform 9 and isoform 11. 3 PublicationsAdd BLAST21
Alternative sequenceiVSP_058423426 – 632EVDQL…VNGVP → LQQRKRGRASCAEETDGGVE GEEEDKEEEDVEEASKETTI TPEQIIVHVIQERLKEEQQM DPFRSELTAIMKGVSTLKHY RIPPVKVVGCARVKIVTRRK RSQTAWMVSNHS in isoform 10 and isoform 11. 1 PublicationAdd BLAST207
Alternative sequenceiVSP_002825491 – 515Missing in isoform 4, isoform 5 and isoform 8. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_002824491 – 502Missing in isoform 2 and isoform 3. CuratedAdd BLAST12
Alternative sequenceiVSP_002826580 – 596Missing in isoform 1, isoform 3, isoform 5 and isoform 7. CuratedAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29074 Genomic DNA. Translation: AAB18828.1.
L29074 Genomic DNA. Translation: AAB18829.1.
L29074 Genomic DNA. Translation: AAB18830.1.
L29074 Genomic DNA. Translation: AAB18831.1.
L29074 Genomic DNA. Translation: AAB18832.1.
L29074 Genomic DNA. Translation: AAB18833.1.
KJ534836 mRNA. Translation: AHW56476.1.
CH471171 Genomic DNA. Translation: EAW61294.1.
CH471171 Genomic DNA. Translation: EAW61296.1.
CH471171 Genomic DNA. Translation: EAW61298.1.
CH471171 Genomic DNA. Translation: EAW61301.1.
CH471171 Genomic DNA. Translation: EAW61302.1.
CH471171 Genomic DNA. Translation: EAW61303.1.
BC086957 mRNA. Translation: AAH86957.1.
M67468 mRNA. Translation: AAA52458.1. Different initiation.
X69962 mRNA. Translation: CAA49586.1.
S65791 mRNA. Translation: AAB28395.2.
L19476 Genomic DNA. Translation: AAA62452.2.
L19477 Genomic DNA. Translation: AAA62453.1.
L19478 Genomic DNA. Translation: AAA62454.1.
L19479 Genomic DNA. Translation: AAA62455.1.
L19480 Genomic DNA. Translation: AAA62456.1.
L19481 Genomic DNA. Translation: AAA62457.1.
L19482 Genomic DNA. Translation: AAA62458.1.
L19483 Genomic DNA. Translation: AAA62459.1.
L19484 Genomic DNA. Translation: AAA62460.1.
L19485 Genomic DNA. Translation: AAA62461.1.
L19486 Genomic DNA. Translation: AAA62462.1.
L19487 Genomic DNA. Translation: AAA62463.1.
L19488 Genomic DNA. Translation: AAA62464.1.
L19489 Genomic DNA. Translation: AAA62465.1.
L19490 Genomic DNA. Translation: AAA62466.1. Sequence problems.
L19491 Genomic DNA. Translation: AAA62467.1. Sequence problems.
L19492 Genomic DNA. Translation: AAA62468.1.
L19493 Genomic DNA. Translation: AAA62469.1.
S76590 Genomic DNA. Translation: AAD14228.1.
CCDSiCCDS14682.1. [Q06787-1]
CCDS55518.1. [Q06787-10]
CCDS55519.1. [Q06787-9]
CCDS76039.1. [Q06787-8]
PIRiI68614.
S45243. A40724.
RefSeqiNP_001172004.1. NM_001185075.1. [Q06787-10]
NP_001172005.1. NM_001185076.1. [Q06787-9]
NP_001172010.1. NM_001185081.1. [Q06787-11]
NP_001172011.1. NM_001185082.1. [Q06787-8]
NP_002015.1. NM_002024.5. [Q06787-1]
UniGeneiHs.103183.

Genome annotation databases

EnsembliENST00000218200; ENSP00000218200; ENSG00000102081. [Q06787-9]
ENST00000370470; ENSP00000359501; ENSG00000102081. [Q06787-6]
ENST00000370471; ENSP00000359502; ENSG00000102081. [Q06787-10]
ENST00000370475; ENSP00000359506; ENSG00000102081. [Q06787-1]
ENST00000440235; ENSP00000413764; ENSG00000102081. [Q06787-8]
GeneIDi2332.
KEGGihsa:2332.
UCSCiuc004fck.5. human. [Q06787-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFMR1_HUMAN
AccessioniPrimary (citable) accession number: Q06787
Secondary accession number(s): A6NNH4
, D3DWT0, D3DWT1, D3DWT2, G8JL90, Q16578, Q5PQZ6, Q99054
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: August 30, 2017
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families