Synaptic functional regulator FMR1 (Fragile X mental retardation protein 1) (FMRP) (Protein FMR-1)
1_MEELV 6_ VEVRG 11_ SNGAF 16_ YKAFV 21_ KDVHE 26_ DSITV 31_ AFENN 36_ WQPDR 41_ QIPFH 46_ DVRFP 51_ PPVGY 56_ NKDIN 61_ ESDEV 66_ EVYSR 71_ ANEKE 76_ PCCWW 81_ LAKVR 86_ MIKGE 91_ FYVIE 96_ YAACD 101_ ATYNE 106_ IVTIE 111_ RLRSV 116_ NPNKP 121_ ATKDT 126_ FHKIK 131_ LDVPE 136_ DLRQM 141_ CAKEA 146_ AHKDF 151_ KKAVG 156_ AFSVT 161_ YDPEN 166_ YQLVI 171_ LSINE 176_ VTSKR 181_ AHMLI 186_ DMHFR 191_ SLRTK 196_ LSLIM 201_ RNEEA 206_ SKQLE 211_ SSRQL 216_ ASRFH 221_ EQFIV 226_ REDLM 231_ GLAIG 236_ THGAN 241_ IQQAR 246_ KVPGV 251_ TAIDL 256_ DEDTC 261_ TFHIY 266_ GEDQD 271_ AVKKA 276_ RSFLE 281_ FAEDV 286_ IQVPR 291_ NLVGK 296_ VIGKN 301_ GKLIQ 306_ EIVDK 311_ SGVVR 316_ VRIEA 321_ ENEKN 326_ VPQEE 331_ EIMPP 336_ NSLPS 341_ NNSRV 346_ GPNAP 351_ EEKKH 356_ LDIKE 361_ NSTHF 366_ SQPNS 371_ TKVQR 376_ VLVAS 381_ SVVAG 386_ ESQKP 391_ ELKAW 396_ QGMVP 401_ FVFVG 406_ TKDSI 411_ ANATV 416_ LLDYH 421_ LNYLK 426_ EVDQL 431_ RLERL 436_ QIDEQ 441_ LRQIG 446_ ASSRP 451_ PPNRT 456_ DKEKS 461_ YVTDD 466_ GQGMG 471_ RGSRP 476_ YRNRG 481_ HGRRG 486_ PGYTS 491_ GTNSE 496_ ASNAS 501_ ETESD 506_ HRDEL 511_ SDWSL 516_ APTEE 521_ ERESF 526_ LRRGD 531_ GRRRG 536_ GGGRG 541_ QGGRG 546_ RGGGF 551_ KGNDD 556_ HSRTD 561_ NRPRN 566_ PREAK 571_ GRTTD 576_ GSLQI 581_ RVDCN 586_ NERSV 591_ HTKTL 596_ QNTSS 601_ EGSRL 606_ RTGKD 611_ RNQKK 616_ EKPDS 621_ VDGQQ 626_PLVNG
1: 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). Also binds 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)
2: 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)
3: 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)
4: (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