UniProtKB - Q06787 (FMR1_HUMAN)
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Protein
Synaptic functional regulator FMR1
Gene
FMR1
Organism
Homo sapiens (Human)
Status
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
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
- nervous system development Source: UniProtKB-KW
- 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
Keywordsi
Molecular function | Activator, Repressor, Ribonucleoprotein, RNA-binding |
Biological process | DNA damage, Host-virus interaction, mRNA processing, mRNA splicing, mRNA transport, Neurogenesis, RNA-mediated gene silencing, Translation regulation, Transport |
Enzyme and pathway databases
SIGNORi | Q06787. |
Names & Taxonomyi
Protein namesi | Recommended name: Synaptic functional regulator FMR1CuratedAlternative name(s): Fragile X mental retardation protein 1Imported Short name: FMRP1 Publication Short name: Protein FMR-11 Publication |
Gene namesi | Name:FMR1Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000102081.13. |
HGNCi | HGNC:3775. FMR1. |
MIMi | 309550. gene. |
neXtProti | NX_Q06787. |
Subcellular locationi
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Centromere, Chromosome, Cytoplasm, Membrane, Nucleus, Postsynaptic cell membrane, Synapse, SynaptosomePathology & Biotechi
Involvement in diseasei
Fragile X syndrome (FXS)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA X-linked dominant disease 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 patients results from an amplification of a CGG repeat region in the FMR1 gene and abnormal methylation.
See also OMIM:300624Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064507 | 138 | R → Q in FXS; 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_075977 | 266 | G → E in FXS; reduces association with polyribosome; reduces RNA-binding. 1 Publication | 1 | |
Natural variantiVAR_005234 | 304 | I → N in FXS; 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:300623Premature 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:311360Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 102 | T → A: Reduces binding to nucleosome. 1 Publication | 1 | |
Mutagenesisi | 103 | Y → L: Reduces binding to nucleosome. 1 Publication | 1 | |
Mutagenesisi | 125 – 126 | TF → AA: Alters the structural integrity of the N-terminus and leads to aggregation. 1 Publication | 2 | |
Mutagenesisi | 500 | S → A: Loss of phosphorylation. Does not affect interaction with MCRS1. Does not affect localization to cytoplasmic granules. Does not affect association with polyribosome. 3 Publications | 1 | |
Mutagenesisi | 500 | S → D: Does not affect RNA-binding to G-quadruplex structure. 1 Publication | 1 | |
Mutagenesisi | 527 – 534 | RRGDGRRR → EEGDGEEE: Reduces nucleolar localization. Strongly reduces nucleolar localization; when associated with 613-E--E-617. 1 Publication | 8 | |
Mutagenesisi | 544 | R → K: Reduces arginine methylation by 80%. 1 Publication | 1 | |
Mutagenesisi | 546 | R → K: Slightly reduced methylation. 1 Publication | 1 | |
Mutagenesisi | 613 – 617 | QKKEK → EEEEE: Reduces nucleolar localization. Strongly reduces nucleolar localization; when associated with 527-E--E-534. 1 Publication | 5 |
Keywords - Diseasei
Disease mutation, Mental retardation, Premature ovarian failureOrganism-specific databases
DisGeNETi | 2332. |
GeneReviewsi | FMR1. |
MalaCardsi | FMR1. |
MIMi | 300623. phenotype. 300624. phenotype. 311360. phenotype. 616034. phenotype. |
OpenTargetsi | ENSG00000102081. |
Orphaneti | 908. Fragile X syndrome. 93256. Fragile X-associated tremor/ataxia syndrome. 619. Primary ovarian failure. 261483. Xq27.3q28 duplication syndrome. |
PharmGKBi | PA28191. |
Polymorphism and mutation databases
BioMutai | FMR1. |
DMDMi | 544328. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000050102 | 1 – 632 | Synaptic functional regulator FMR1Add BLAST | 632 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 337 | PhosphoserineBy similarity | 1 | |
Modified residuei | 370 | PhosphoserineCombined sources | 1 | |
Modified residuei | 463 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 471 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 500 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 544 | Omega-N-methylarginine1 Publication | 1 | |
Modified residuei | 620 | PhosphoserineBy similarity | 1 |
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 conjugationProteomic databases
EPDi | Q06787. |
MaxQBi | Q06787. |
PaxDbi | Q06787. |
PeptideAtlasi | Q06787. |
PRIDEi | Q06787. |
PTM databases
iPTMneti | Q06787. |
PhosphoSitePlusi | Q06787. |
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
Bgeei | ENSG00000102081. |
CleanExi | HS_FMR1. |
ExpressionAtlasi | Q06787. baseline and differential. |
Genevisiblei | Q06787. HS. |
Organism-specific databases
HPAi | CAB012444. 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). Interacts with HABP4 (PubMed:21771594).By similarity31 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
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
Protein-protein interaction databases
BioGridi | 108619. 64 interactors. |
DIPi | DIP-29509N. |
IntActi | Q06787. 46 interactors. |
MINTi | Q06787. |
STRINGi | 9606.ENSP00000359506. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 5 – 9 | Combined sources | 5 | |
Beta strandi | 15 – 23 | Combined sources | 9 | |
Beta strandi | 25 – 32 | Combined sources | 8 | |
Helixi | 33 – 35 | Combined sources | 3 | |
Beta strandi | 40 – 43 | Combined sources | 4 | |
Helixi | 44 – 46 | Combined sources | 3 | |
Beta strandi | 64 – 69 | Combined sources | 6 | |
Beta strandi | 71 – 75 | Combined sources | 5 | |
Beta strandi | 78 – 88 | Combined sources | 11 | |
Beta strandi | 91 – 97 | Combined sources | 7 | |
Helixi | 100 – 103 | Combined sources | 4 | |
Beta strandi | 104 – 108 | Combined sources | 5 | |
Helixi | 109 – 111 | Combined sources | 3 | |
Beta strandi | 112 – 114 | Combined sources | 3 | |
Turni | 123 – 125 | Combined sources | 3 | |
Beta strandi | 127 – 132 | Combined sources | 6 | |
Turni | 135 – 138 | Combined sources | 4 | |
Helixi | 139 – 141 | Combined sources | 3 | |
Helixi | 144 – 147 | Combined sources | 4 | |
Helixi | 148 – 154 | Combined sources | 7 | |
Beta strandi | 157 – 162 | Combined sources | 6 | |
Turni | 163 – 166 | Combined sources | 4 | |
Beta strandi | 167 – 173 | Combined sources | 7 | |
Helixi | 177 – 198 | Combined sources | 22 | |
Beta strandi | 220 – 224 | Combined sources | 5 | |
Helixi | 227 – 229 | Combined sources | 3 | |
Helixi | 230 – 234 | Combined sources | 5 | |
Helixi | 236 – 238 | Combined sources | 3 | |
Helixi | 239 – 245 | Combined sources | 7 | |
Beta strandi | 250 – 256 | Combined sources | 7 | |
Turni | 257 – 260 | Combined sources | 4 | |
Beta strandi | 261 – 268 | Combined sources | 8 | |
Helixi | 269 – 279 | Combined sources | 11 | |
Beta strandi | 281 – 289 | Combined sources | 9 | |
Helixi | 290 – 292 | Combined sources | 3 | |
Helixi | 293 – 297 | Combined sources | 5 | |
Helixi | 299 – 301 | Combined sources | 3 | |
Helixi | 302 – 311 | Combined sources | 10 | |
Beta strandi | 314 – 321 | Combined sources | 8 | |
Beta strandi | 398 – 406 | Combined sources | 9 | |
Helixi | 407 – 422 | Combined sources | 16 | |
Helixi | 432 – 434 | Combined sources | 3 | |
Beta strandi | 535 – 538 | Combined sources | 4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2BKD | NMR | - | N | 1-134 | [»] | |
2FMR | NMR | - | A | 216-280 | [»] | |
2LA5 | NMR | - | B | 527-541 | [»] | |
2QND | X-ray | 1.90 | A/B | 216-425 | [»] | |
4OVA | X-ray | 3.00 | A/B/C/D | 1-209 | [»] | |
4QVZ | X-ray | 3.20 | A/B | 1-213 | [»] | |
4QW2 | X-ray | 2.99 | A/B | 1-213 | [»] | |
5DE5 | X-ray | 3.00 | B/D | 528-544 | [»] | |
5DE8 | X-ray | 3.10 | B/D | 528-544 | [»] | |
5DEA | X-ray | 2.80 | B/D | 528-544 | [»] | |
5UWJ | X-ray | 2.22 | D | 423-437 | [»] | |
5UWO | X-ray | 2.35 | D | 422-438 | [»] | |
DisProti | DP00134. | |||||
ProteinModelPortali | Q06787. | |||||
SMRi | Q06787. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q06787. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 50 | Agenet-like 1PROSITE-ProRule annotationAdd BLAST | 47 | |
Domaini | 63 – 115 | Agenet-like 2PROSITE-ProRule annotationAdd BLAST | 53 | |
Domaini | 222 – 251 | KH 1PROSITE-ProRule annotationAdd BLAST | 30 | |
Domaini | 285 – 314 | KH 2PROSITE-ProRule annotationAdd BLAST | 30 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 184 | Required for nuclear localizationBy similarityAdd BLAST | 184 | |
Regioni | 172 – 211 | Necessary for interaction with CYFIP1, CYFIP2, FXR1 and FXR2By similarity2 PublicationsAdd BLAST | 40 | |
Regioni | 397 – 491 | Required for nuclear export2 PublicationsAdd BLAST | 95 | |
Regioni | 419 – 632 | Interaction with RANBP91 PublicationAdd BLAST | 214 | |
Regioni | 534 – 548 | RNA-binding RGG-boxAdd BLAST | 15 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 424 – 443 | Nuclear export signalBy similarityAdd BLAST | 20 | |
Motifi | 527 – 534 | Nucleolar localization signal 11 Publication | 8 | |
Motifi | 613 – 617 | Nucleolar localization signal 21 Publication | 5 |
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
RepeatPhylogenomic databases
eggNOGi | ENOG410IF9J. Eukaryota. ENOG410ZDJG. LUCA. |
GeneTreei | ENSGT00390000017033. |
HOVERGENi | HBG005739. |
InParanoidi | Q06787. |
KOi | K15516. |
OMAi | NERETCG. |
OrthoDBi | EOG091G08EZ. |
PhylomeDBi | Q06787. |
TreeFami | TF105427. |
Family and domain databases
Gene3Di | 3.30.1370.10. 1 hit. |
InterProi | View protein in InterPro IPR008395. Agenet-like_dom. IPR032196. FXMR_C2. IPR022034. FXMRP1_C_core. IPR004087. KH_dom. IPR004088. KH_dom_type_1. IPR036612. KH_dom_type_1_sf. |
Pfami | View protein in Pfam PF05641. Agenet. 1 hit. PF16098. FXMR_C2. 1 hit. PF12235. FXMRP1_C_core. 1 hit. PF00013. KH_1. 2 hits. |
SMARTi | View protein in SMART SM00322. KH. 2 hits. |
SUPFAMi | SSF54791. SSF54791. 2 hits. |
PROSITEi | View protein in PROSITE PS51641. AGENET_LIKE. 2 hits. PS50084. KH_TYPE_1. 2 hits. |
s (11)i Sequence
Sequence statusi: Complete.
This entry describes 11 produced by isoformsialternative 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.
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
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
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
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 294 – 295 | Missing in AAA52458 (PubMed:1710175).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064507 | 138 | R → Q in FXS; 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_029278 | 145 | A → S. Corresponds to variant dbSNP:rs29281Ensembl. | 1 | |
Natural variantiVAR_075977 | 266 | G → E in FXS; reduces association with polyribosome; reduces RNA-binding. 1 Publication | 1 | |
Natural variantiVAR_005234 | 304 | I → N in FXS; 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_005235 | 546 | R → H1 PublicationCorresponds to variant dbSNP:rs782651077Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_002823 | 376 – 396 | Missing in isoform 1, isoform 8, isoform 9 and isoform 11. 3 PublicationsAdd BLAST | 21 | |
Alternative sequenceiVSP_058423 | 426 – 632 | EVDQL…VNGVP → LQQRKRGRASCAEETDGGVE GEEEDKEEEDVEEASKETTI TPEQIIVHVIQERLKEEQQM DPFRSELTAIMKGVSTLKHY RIPPVKVVGCARVKIVTRRK RSQTAWMVSNHS in isoform 10 and isoform 11. 1 PublicationAdd BLAST | 207 | |
Alternative sequenceiVSP_002825 | 491 – 515 | Missing in isoform 4, isoform 5 and isoform 8. 1 PublicationAdd BLAST | 25 | |
Alternative sequenceiVSP_002824 | 491 – 502 | Missing in isoform 2 and isoform 3. CuratedAdd BLAST | 12 | |
Alternative sequenceiVSP_002826 | 580 – 596 | Missing in isoform 1, isoform 3, isoform 5 and isoform 7. CuratedAdd BLAST | 17 |
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. |
CCDSi | CCDS14682.1. [Q06787-1] CCDS55518.1. [Q06787-10] CCDS55519.1. [Q06787-9] CCDS76039.1. [Q06787-8] |
PIRi | I68614. S45243. A40724. |
RefSeqi | NP_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] |
UniGenei | Hs.103183. |
Genome annotation databases
Ensembli | ENST00000218200; ENSP00000218200; ENSG00000102081. [Q06787-9] ENST00000370470; ENSP00000359501; ENSG00000102081. [Q06787-6] ENST00000370471; ENSP00000359502; ENSG00000102081. [Q06787-10] ENST00000370475; ENSP00000359506; ENSG00000102081. [Q06787-1] ENST00000440235; ENSP00000413764; ENSG00000102081. [Q06787-8] |
GeneIDi | 2332. |
KEGGi | hsa:2332. |
UCSCi | uc004fck.5. human. [Q06787-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | FMR1_HUMAN | |
Accessioni | Q06787Primary (citable) accession number: Q06787 Secondary accession number(s): A6NNH4 Q99054 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | June 1, 1994 | |
Last modified: | March 28, 2018 | |
This is version 196 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |