NucEnvDB

NucEnvDB

A database of Nuclear Envelope Proteins and their Interactions

Fragile X messenger ribonucleoprotein 1 - Rattus norvegicus - NucEnvDB

Fragile X messenger ribonucleoprotein 1 (Rattus norvegicus)

FASTA TEXT XML

Subcellular Location Biology & Function Interactions Cross-References

General Information

Protein Information
Protein Name	Fragile X messenger ribonucleoprotein 1
Accession Code	Q80WE1
Gene	Fmr1
Organism	Rattus norvegicus \| Norway rat (Taxonomy: 10116)
Part of Reference Proteome?	Yes
Sequence (Length: 593)
MEELVVEVRGSNGAFYKAFVKDVHEDSITVAFENNWQPERQIPFHDVRFPPPVGYNKDINESDEVEVYSRANEKEPCCWWLAKVRMIKGEFYVIEYAACDATYNEIVTIERLRSVNPNKPATKDTFHKIK LEVPEDLRQMCAKESAHKDFKKAVGAFSVTYDPENYQLVILSINEVTSKRAHMLIDMHFRSLRTKLSLILRNEEASKQLESSRQLASRFHEQFIVREDLMGLAIGTHGANIQQARKVPGVTAIDLDEDTC TFHIYGEDQDAVKKARSFLEFAEDVIQVPRNLVGKVIGKNGKLIQEIVDKSGVVRVRIEAENEKSVPQEEENLPPSSLPSNNSRVGSNSSEEKKHLDTKENTHFSQPNSTKVQRGMVPFVFVGTKDSIAN ATVLLDYHLNYLKEVDQLRLERLQIDEQLRQIGASSRPPPNRTDKEKGYVTDDGQGMGRGSRPYRNRGHGRRGPGYTSGTNSEASNASETESDHRDELSDWSLAPTEEERESFLRRGDGRRRGGGGRGQG GRGRGGGFKGNDDHSRTDNRPRNPRETKGRTTDGSLQSTSSEGSRLRTGKDRNQKKEKPDSVDGLQPLVNGVP

Subcellular Location

Description
Nucleus {Experimental EvidencePubMed:9030614}. Nucleus, nucleolus {By SimilarityUniProtKB:Q06787}. Chromosome, centromere {By SimilarityUniProtKB:P35922}. Chromosome {By SimilarityUniProtKB:P35922}. Cytoplasm, perinuclear region {By SimilarityUniProtKB:P35922}. Perikaryon {Experimental EvidencePubMed:14613971, Experimental EvidencePubMed:15028757, Experimental EvidencePubMed:15564573, Experimental EvidencePubMed:16571602, Experimental EvidencePubMed:24709664, Experimental EvidencePubMed:9030614, ECO:0000269\|PubMed:9144248}. Cytoplasm, Cytoplasmic ribonucleoprotein granule {Experimental EvidencePubMed:15028757, ECO:0000269\|PubMed:16098134, ECO:0000269\|PubMed:23891804}. Cytoplasm, Stress granule {By SimilarityUniProtKB:Q06787}. Cell projection, neuron projection {Experimental EvidencePubMed:14613971, Experimental EvidencePubMed:24709664}. Cell projection, dendrite {Experimental EvidencePubMed:15028757, Experimental EvidencePubMed:15564573, Experimental EvidencePubMed:16571602, Experimental EvidencePubMed:9030614, ECO:0000269\|PubMed:9144248}. Cell projection, dendritic spine {Experimental EvidencePubMed:15028757, ECO:0000269\|PubMed:16098134, Experimental EvidencePubMed:9030614, ECO:0000269\|PubMed:9144248}. Cell projection, growth cone {ECO:0000269\|PubMed:16098134}. Cell projection, filopodium {ECO:0000269\|PubMed:16098134}. Cell projection, filopodium tip {By SimilarityUniProtKB:P35922}. Cell projection, axon {Experimental EvidencePubMed:9030614}. Synapse {Experimental EvidencePubMed:15028757}. Synapse, synaptosome {Experimental EvidencePubMed:15564573, Experimental EvidencePubMed:24709664, Experimental EvidencePubMed:9030614, ECO:0000269\|PubMed:9144248}. Postsynaptic density {ECO:0000269\|PubMed:9144248}. Presynaptic cell membrane {By SimilarityUniProtKB:P35922}. Cell membrane {By SimilarityUniProtKB:P35922}. Note=Colocalizes with H2AX/H2A.x in pericentromeric heterochromatin in response to DNA damaging agents (By similarity). Localizes on meiotic pachytene-stage chromosomes (By similarity). Forms nuclear foci representing sites of ongoing DNA replication in response to DNA damaging agents (By similarity). Shuttles between nucleus and cytoplasm in a XPO1/CRM1-dependent manner (By similarity). Localizes to cytoplasmic granules, also referred to as messenger ribonucleoprotein particles or mRNPs, along dendrites and dendritic spines (PubMed:15028757, PubMed:23891804). FMR1-containing cytoplasmic granules colocalize to F-actin-rich structures, including filopodium, spines and growth cone during the development of hippocampal neurons (PubMed:16098134). FMR1-containing cytoplasmic granules are transported out of the soma along axon and dendrite to synaptic contacts in a microtubule- and kinesin-dependent manner (PubMed:16098134). Colocalizes with CACNA1B in the cytoplasm and at the cell membrane of neurons (By similarity). Colocalizes with CYFIP1, CYFIP2, NXF2 and ribosomes in the perinuclear region (By similarity). Colocalizes with CYFIP1 and EIF4E in dendrites and probably at synapses (By similarity). Colocalizes with FXR1, kinesin, 60S acidic ribosomal protein RPLP0 and SMN in cytoplasmic granules in the soma and neurite cell processes (By similarity). Colocalizes with FXR1 and FXR2 in discrete granules, called fragile X granules (FXGs), along axon and presynaptic compartments (By similarity). Colocalizes with TDRD3 in cytoplasmic stress granules (SGs) in response to various cellular stress (By similarity). {By SimilarityUniProtKB:P35922, By SimilarityUniProtKB:Q06787, Experimental EvidencePubMed:15028757, ECO:0000269\|PubMed:16098134, ECO:0000269\|PubMed:23891804}.
Position in the Nuclear Envelope
Location	Location ID	Description
Perinuclear Region	SL-0198	The perinuclear region is the cytoplasmic region just around the nucleus.
Membrane Topology
Topology	Source	Annotation Type
Unknown	UniProt	Sequence Analysis
Assigned Ontology terms

Cellular Component	Anchoring Junction (GO:0070161) Axon (GO:0030424) Axon Cytoplasm (GO:1904115) Axon Terminus (GO:0043679) Cajal Body (GO:0015030) Cell Body (GO:0044297) Cell Projection (GO:0042995) Chromocenter (GO:0010369) Chromosome (GO:0005694) Chromosome, Centromeric Region (GO:0000775) Cytoplasm (GO:0005737) Cytoplasmic Ribonucleoprotein Granule (GO:0036464) Cytoplasmic Stress Granule (GO:0010494) Cytosol (GO:0005829) Dendrite (GO:0030425) Dendritic Filopodium (GO:1902737) Dendritic Spine (GO:0043197) Dendritic Spine Head (GO:0044327) Dendritic Spine Neck (GO:0044326) Extrinsic Component Of Plasma Membrane (GO:0019897) Filopodium Tip (GO:0032433) Glial Cell Projection (GO:0097386) Glutamatergic Synapse (GO:0098978) Growth Cone (GO:0030426) Growth Cone Filopodium (GO:1990812) Hippocampal Mossy Fiber To CA3 Synapse (GO:0098686) Membrane (GO:0016020) Messenger Ribonucleoprotein Complex (GO:1990124) Microtubule Cytoskeleton (GO:0015630) MRNA Cap Binding Complex (GO:0005845) Neuron Projection (GO:0043005) Neuronal Cell Body (GO:0043025) Neuronal Ribonucleoprotein Granule (GO:0071598) Nucleolus (GO:0005730) Nucleoplasm (GO:0005654) Nucleus (GO:0005634) Perikaryon (GO:0043204) Perinuclear Region Of Cytoplasm (GO:0048471) Polysome (GO:0005844) Postsynapse (GO:0098794) Postsynaptic Cytosol (GO:0099524) Postsynaptic Density (GO:0014069) Presynapse (GO:0098793) Presynaptic Cytosol (GO:0099523) Presynaptic Membrane (GO:0042734) Proximal Dendrite (GO:1990635) Ribonucleoprotein Complex (GO:1990904) Rough Endoplasmic Reticulum (GO:0005791) Schaffer Collateral - CA1 Synapse (GO:0098685) SMN Complex (GO:0032797) Smooth Endoplasmic Reticulum (GO:0005790) Spine Apparatus (GO:0097444) Synapse (GO:0045202) Terminal Bouton (GO:0043195)

Biology & Function

Description
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:9144248). Plays a role in the alternative splicing of its own mRNA (By similarity). 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:9144248). 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 (By similarity). 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 (By similarity). Facilitates the assembly of miRNAs on specific target mRNAs (By similarity). Also plays a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (By similarity). 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 (By similarity). 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 (By similarity). Binds to intramolecular G- quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (By similarity). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (By similarity). Binds also to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (By similarity). Binds mRNAs containing U-rich target sequences (By similarity). 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 (By similarity). 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 (By similarity). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (By similarity). 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) (By similarity). Moreover, plays a role in the modulation of the sodium-activated potassium channel KCNT1 gating activity (By similarity). 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 (PubMed:24709664). 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 (By similarity). 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 (By similarity). {By SimilarityUniProtKB:P35922, By SimilarityUniProtKB:Q06787, Experimental EvidencePubMed:24709664, Experimental EvidencePubMed:9144248}.
Assigned Ontology terms

Biological Process	Anterograde Axonal Transport (GO:0008089) Cellular Response To DNA Damage Stimulus (GO:0006974) Cellular Response To Hydroxyurea (GO:0072711) Cellular Response To Monosodium Glutamate (GO:1904009) Cellular Response To Potassium Ion (GO:0035865) Cellular Response To UV (GO:0034644) Cellular Response To Virus (GO:0098586) Central Nervous System Development (GO:0007417) Dendritic Spine Development (GO:0060996) Detection Of Mechanical Stimulus Involved In Sensory Perception (GO:0050974) DNA Repair (GO:0006281) Excitatory Chemical Synaptic Transmission (GO:0098976) RNA-Mediated Gene Silencing (GO:0031047) Glutamate Receptor Signaling Pathway (GO:0007215) Inhibitory Chemical Synaptic Transmission (GO:0098977) Modulation By Host Of Viral RNA Genome Replication (GO:0044830) MRNA Processing (GO:0006397) MRNA Transport (GO:0051028) Negative Regulation Of Cytoplasmic Translation (GO:2000766) Negative Regulation Of Gene Expression (GO:0010629) Negative Regulation Of Long-Term Synaptic Depression (GO:1900453) Negative Regulation Of MRNA Catabolic Process (GO:1902373) Negative Regulation Of Neuron Apoptotic Process (GO:0043524) Negative Regulation Of Neuron Differentiation (GO:0045665) Negative Regulation Of Protein Processing (GO:0010955) Negative Regulation Of Receptor Internalization (GO:0002091) Negative Regulation Of Synaptic Vesicle Exocytosis (GO:2000301) Negative Regulation Of Translation (GO:0017148) Negative Regulation Of Translational Initiation (GO:0045947) Negative Regulation Of Voltage-Gated Calcium Channel Activity (GO:1901386) Ovarian Follicle Development (GO:0001541) Positive Regulation Of Dendritic Spine Development (GO:0060999) Positive Regulation Of Filopodium Assembly (GO:0051491) Positive Regulation Of Gene Expression (GO:0010628) Positive Regulation Of Intracellular Transport Of Viral Material (GO:1901254) Positive Regulation Of Long-Term Neuronal Synaptic Plasticity (GO:0048170) Positive Regulation Of Long-Term Synaptic Depression (GO:1900454) Positive Regulation Of Long-Term Synaptic Potentiation (GO:1900273) Positive Regulation Of MiRNA-Mediated Gene Silencing (GO:2000637) Positive Regulation Of MRNA Binding (GO:1902416) Positive Regulation Of Proteasomal Protein Catabolic Process (GO:1901800) Positive Regulation Of Protein Phosphorylation (GO:0001934) Positive Regulation Of Receptor Internalization (GO:0002092) Positive Regulation Of Response To DNA Damage Stimulus (GO:2001022) Positive Regulation Of Synaptic Transmission (GO:0050806) Positive Regulation Of Translation (GO:0045727) Regulation Of Alternative MRNA Splicing, Via Spliceosome (GO:0000381) Regulation Of Dendritic Spine Development (GO:0060998) Regulation Of Filopodium Assembly (GO:0051489) Regulation Of MiRNA-Mediated Gene Silencing (GO:0060964) Regulation Of Modification Of Synaptic Structure (GO:1905244) Regulation Of MRNA Stability (GO:0043488) Regulation Of Neuronal Action Potential (GO:0098908) Regulation Of Neurotransmitter Secretion (GO:0046928) Regulation Of Translation (GO:0006417) Regulation Of Translation At Postsynapse, Modulating Synaptic Transmission (GO:0099578) Regulation Of Translation At Presynapse, Modulating Synaptic Transmission (GO:0099577) Response To Activity (GO:0014823) Response To Cocaine (GO:0042220) Response To Electrical Stimulus (GO:0051602) Response To Gonadotropin (GO:0034698) Response To Interleukin-1 (GO:0070555) Response To Interleukin-17 (GO:0097396) Response To Light Stimulus (GO:0009416) RNA Splicing (GO:0008380) Skeletal Muscle Organ Development (GO:0060538) Social Behavior (GO:0035176) Transmission Of Nerve Impulse (GO:0019226)
Molecular Function	Chromatin Binding (GO:0003682) Dynein Complex Binding (GO:0070840) G-Quadruplex RNA Binding (GO:0002151) Identical Protein Binding (GO:0042802) Methylated Histone Binding (GO:0035064) Microtubule Binding (GO:0008017) MiRNA Binding (GO:0035198) MRNA 3'-UTR Binding (GO:0003730) MRNA 5'-UTR Binding (GO:0048027) MRNA Binding (GO:0003729) Poly(G) Binding (GO:0034046) Poly(U) RNA Binding (GO:0008266) Protein Domain Specific Binding (GO:0019904) Protein Heterodimerization Activity (GO:0046982) Protein Homodimerization Activity (GO:0042803) Protein Kinase Binding (GO:0019901) Protein Phosphatase Binding (GO:0019903) Ribosome Binding (GO:0043022) RNA 7-Methylguanosine Cap Binding (GO:0000340) RNA Binding (GO:0003723) RNA Stem-Loop Binding (GO:0035613) RNA Strand Annealing Activity (GO:0033592) Sequence-Specific MRNA Binding (GO:1990825) SiRNA Binding (GO:0035197) Translation Initiation Factor Binding (GO:0031369) Translation Regulator Activity (GO:0045182) Translation Repressor Activity (GO:0030371) Transmembrane Transporter Binding (GO:0044325)

Protein-Protein Interactions

Interactions with other proteins (2 interactors)

Partner (UniProt)		IntAct	Confidence score
Q9R0N3	Synaptotagmin-11 (Synaptotagmin XI) (SytXI)	EBI-9526900	0.35
F1M0Z1	Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein)	EBI-26961439	0.35

Cross-References

Database	Links
UNIPROT	Q80WE1 P70568
Pfam	PF05641 PF16098 PF12235 PF00013 PF17904 PF18336
PROSITE	PS51641 PS50084

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