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IID00719
UniprotQ06787
ProteinSynaptic functional regulator FMR1
GeneFMR1
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
632
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 1-134 Monomer :
 Evidence NMR 2bkd N Reference
       Region 2bkd N 1-134 order
Seq 1-209 Homo tetramer :
 Evidence X-RAY 4ova D Reference
       Region 4ova D 1-200 order
       Region 4ova D 201-209 disorder
 Evidence X-RAY 4ova C Reference
       Region 4ova C 1-199 order
       Region 4ova C 200-209 disorder
 Evidence X-RAY 4ova B Reference
       Region 4ova B 1-200 order
       Region 4ova B 201-209 disorder
 Evidence X-RAY 4ova A Reference
       Region 4ova A 1-200 order
       Region 4ova A 201-209 disorder
Seq 1-213 Monomer :
 Evidence X-RAY 4qw2 B Reference
       Region 4qw2 B 1-2 disorder
       Region 4qw2 B 3-202 order
       Region 4qw2 B 203-213 disorder
 Evidence X-RAY 4qw2 A Reference
       Region 4qw2 A 1-1 disorder
       Region 4qw2 A 2-99 order
       Region 4qw2 A 100-101 disorder
       Region 4qw2 A 102-201 order
       Region 4qw2 A 202-213 disorder
 Evidence X-RAY 4qvz B Reference
       Region 4qvz B 1-98 order
       Region 4qvz B 99-101 disorder
       Region 4qvz B 102-207 order
       Region 4qvz B 208-213 disorder
 Evidence X-RAY 4qvz A Reference
       Region 4qvz A 1-1 disorder
       Region 4qvz A 2-97 order
       Region 4qvz A 98-103 disorder
       Region 4qvz A 104-201 order
       Region 4qvz A 202-213 disorder
Seq 216-280 Monomer :
 Evidence NMR 2fmr A Reference
       Region 2fmr A 216-280 order
       Region 2fmr A 232-237 high_rmsd
Seq 216-330,397-425 Monomer :
 Evidence X-RAY 2qnd B Reference
       Region 2qnd B 216-216 disorder
       Region 2qnd B 217-330 order
       Region 2qnd B 397-425 order
 Evidence X-RAY 2qnd A Reference
       Region 2qnd A 216-218 disorder
       Region 2qnd A 219-330 order
       Region 2qnd A 397-425 order
Seq 422-438 Hetero tetramer : IID50169Complex
 Evidence X-RAY 5uwo D Reference
       Region 5uwo D 422-429 disorder
       Region 5uwo D 430-438 order
 Evidence X-RAY 5uwj D Reference
       Region 5uwj D 423-426 disorder
       Region 5uwj D 427-437 order
Seqdisorder 527-541
 Evidence Reference
       Region 527-541 disorder
Seq 527-544 Monomer :
 Evidence NMR 2la5 B Reference
       Region 2la5 B 527-541 order
 Evidence X-RAY 5dea D Reference
       Region 5dea D 528-528 disorder
       Region 5dea D 529-542 order
       Region 5dea D 543-544 disorder
 Evidence X-RAY 5dea B Reference
       Region 5dea B 528-528 disorder
       Region 5dea B 529-542 order
       Region 5dea B 543-544 disorder
 Evidence X-RAY 5de8 D Reference
       Region 5de8 D 528-529 disorder
       Region 5de8 D 530-543 order
       Region 5de8 D 544-544 disorder
 Evidence X-RAY 5de8 B Reference
       Region 5de8 B 528-528 disorder
       Region 5de8 B 529-542 order
       Region 5de8 B 543-544 disorder
 Evidence X-RAY 5de5 D Reference
       Region 5de5 D 528-529 disorder
       Region 5de5 D 530-542 order
       Region 5de5 D 543-544 disorder
 Evidence X-RAY 5de5 B Reference
       Region 5de5 B 528-528 disorder
       Region 5de5 B 529-542 order
       Region 5de5 B 543-544 disorder
SeqProS verified 527-541 :
       Region 2la5 B 527-541 order
       Region 5de8 B 529-542 order
       Region 5de8 D 530-543 order
       Region 5dea B 529-542 order
       Region 5dea D 529-542 order
       Region 5de5 B 529-542 order
       Region 5de5 D 530-542 order
       Region 527-541 disorder
Seqphosphorylation
    337-337 Phosphoserine
    370-370 Phosphoserine
    460-460 Phosphoserine
    463-463 Phosphothreonine
    500-500 Phosphoserine; by CK2
    502-502 Phosphothreonine
    504-504 Phosphoserine
    511-511 Phosphoserine
    514-514 Phosphoserine
    518-518 Phosphothreonine
    573-573 Phosphothreonine
    574-574 Phosphothreonine
    592-592 Phosphothreonine
    594-594 Phosphothreonine
    598-598 Phosphothreonine
    620-620 Phosphoserine
Seqacetylation
    1-1 N-acetylmethionine
 
Prediction
NeProc
Disorder 202-216,342-632
Order 1-201,217-341
ProS 342-379,390-480,485-515,521-524,535-558,564-571,576-584,625-632
AlphaFold
Disorder 1-1,99-102,212-217,320-396,445-632
Order 2-98,103-211,218-319,397-444
Pfam Hmmer
PF05641 59-120 1.5e-09
PF00013 220-279 8.4e-07
PF00013 283-333 2.4e-06
SEG 492-504 ,527-549
Function
Function in SwissProt
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 postsynaptic 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 homomer; 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 H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610).
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.