The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors.
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 homomer poly(G) (PubMed:14532325).
Isoform 10
The C-terminal region contains a Cajal body localization signal at positions 490 through 506 (PubMed:24204304).
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:12417522, PubMed:16631377, PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). 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, PubMed:30765518, PubMed:31439799). 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 (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). 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 (PubMed:31439799). Acts as a repressor of mRNA translation in synaptic regions by mediating formation of neuronal ribonucleoprotein granules and promoting recruitmtent of EIF4EBP2 (PubMed:30765518). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11157796, PubMed:11532944, 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). Also plays 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:11157796, PubMed:11719189, PubMed:12594214, PubMed:17417632, PubMed:23235829, PubMed:24448548, PubMed:7692601). 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:11532944, PubMed:12594214, PubMed:15282548, PubMed:18653529, PubMed:7692601). 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). Plays a role in mRNA nuclear export (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:31753916). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (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 homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:12950170, PubMed:15381419, PubMed:7688265, PubMed:7781595, 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 proteasomal degradation (By similarity). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (By similarity). 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 (PubMed:39106863).
Isoform 10
Binds to RNA homomer; 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).
Isoform 6
Binds to RNA homomer; 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).
(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.
Fragile X syndrome
FXS
An X-linked dominant disease characterized by moderate to severe intellectual disability, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most patients results from an amplification of a CGG repeat region in the FMR1 gene and abnormal methylation.
None
The disease is caused by variants affecting the gene represented in this entry.
Fragile X tremor/ataxia syndrome
FXTAS
An X-linked neurodegenerative disorder characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive decline.
None
The disease is caused by variants affecting the gene represented in this entry.
Premature ovarian failure 1
POF1
An 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Phosphorylated on several serine residues (PubMed:14532325). 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 (PubMed:30765518, PubMed:31439799). Phosphorylation at Ser-500 by CK2 promotes secondary phosphorylation of other nearby serine residues (By similarity). Phosphorylation has no effect on the binding of individual mRNA species (By similarity). Unphosphorylated FMR1 is associated with actively translating polyribosome, whereas a fraction of phosphorylated FMR1 is associated with apparently stalled polyribosome (By similarity). Dephosphorylation by an activated phosphatase may release the FMR1-mediated translational repression and allow synthesis of a locally required protein at synapses (By similarity).
Monoubiquitinated. Polyubiquitinated. Ubiquitinated and targeted for proteasomal degradation after activation of metabotropic glutamate receptor (mGluR).
Monomethylated and asymmetrically dimethylated by PRMT1, PRMT3 and PRMT4 at four arginine residues of the arginine-glycine-glycine box (PubMed:16922515, PubMed:30765518). Methylation decreases ability to undergo liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment (PubMed:30765518). Methylation does not affect mRNA-binding (PubMed:30765518). Methylation is necessary for heterodimerization with FXR1, association with polyribosomes, recruitment into stress granules and translation of FMR1 target mRNAs (PubMed:16636078).
Isoform 10
Undergoes proteolytic cleavage; may be specifically cleaved by calpain-1/CAPN1 in cajal bodies (PubMed:24204304).
Belongs to the FMR1 family.
Expressed in the brain, cerebellum and testis (PubMed:8401578, PubMed:9259278). 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, PubMed:9259278). Expressed in brain, testis and placenta (PubMed:8504300, PubMed:9259278). Expressed in neurons and lymphocytes (PubMed:8504300).
Fragile X messenger ribonucleoprotein 1, Fragile X messenger ribonucleoprotein, Protein FMR-1, FMRP, FMR1
Proteins
Neuroscience
71174Da
We found 17 products in 4 categories
ab259335
Anti-FMRP antibody [EPR23852-90]
ab277489
Anti-FMRP antibody [EPR23852-90] - BSA and Azide free
ab109741
ab264380
ab132093