FMR1 encodes FMRP, an RNA-binding protein that recognizes selected RNA sequences and structures and organizes messenger ribonucleoprotein particles. It regulates the translation, stability and intracellular transport of target mRNAs, with prominent roles in neuronal processes and synapses. Its effects on translation depend on the target RNA and regulatory context and include both repression and activation. The low-complexity region can scaffold RNA-containing condensates, with assembly and translation influenced by phosphorylation, methylation and interacting proteins. FMRP occurs in cytoplasmic RNA complexes and granules, while alternative splicing and cellular conditions permit nuclear and nucleolar pools. FMRP also modulates selected ion-channel complexes and excitability in studied neuronal systems.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IDA PMID:18653529 The G-quartet containing FMRP binding site in FMR1 mRNA is a... | KEEP AS NON CORE | Summary: The original study supports FMRP-dependent changes in Fmr1 splicing. Reason: PMID:18653529 separates the intrinsic splicing-enhancer activity of an FMR1 RNA element from protein-mediated autoregulation. Induction of human FMRP in rat PC12 cells changes endogenous exon usage, and mouse cortex supplies a separate loss-of-function comparison. Retain this limited splicing-regulatory role without assigning general spliceosome catalysis or equating the paper’s isoform numbers with current UniProt products. |
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FMRP can regulate alternative splicing of its own transcript. Reason: The ARBA inference is consistent with PMID:18653529: induced human FMRP in rat PC12 cells changes endogenous Fmr1 splice-form proportions, with a complementary knockout-mouse observation. This is contextual autoregulation rather than a principal spliceosomal activity. The RNA element itself is an exonic splicing enhancer, but its minigene enhancer activity was not detectably altered by the tested FMRP isoforms; those two findings should not be conflated. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centromeric-region association is a conditional chromatin-localization context. Reason: The UniProt subcellular-location mapping is supported by the mouse chromatin work in PMID:24813610: after leptomycin B, FMRP foci occur near peri-centromeric chromocenters, overlap the paper’s CENTB marker, and can wrap chromocenters; aphidicolin increases this signal. Retain the regional association context, with the boundary that peri-centromeric/chromocenter localization is not a demonstrated constitutive kinetochore component or an all-product human localization. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0002092 positive regulation of receptor internalization | IDA PMID:25561520 Independent role for presynaptic FMRP revealed by an FMR1 mi... | MODIFY | Summary: FMRP suppresses excessive AMPA-receptor internalization in the cited rescue experiments. Reason: PMID:25561520 reports restoration of excessive AMPAR internalization in Fmr1-knockout mouse hippocampal neurons by wild-type or R138Q FMRP. The related original PMID:24813610 supplement independently shows the lower internalized/total receptor ratio after rescue. This supports negative, rather than positive, regulation of receptor internalization. The ratio assay does not isolate an endocytosis rate constant, and the earlier paper’s construct identity is not filled from the later study. Preserve the original 2015 citation and source term while correcting the direction in the proposed term. Proposed replacements: negative regulation of receptor internalization |
| GO:0002151 G-quadruplex RNA binding | EXP PMID:21642970 Structure-function studies of FMRP RGG peptide recognition o... | ACCEPT | Summary: The FMRP RGG region recognizes a structured G-quadruplex RNA junction. Reason: PMID:21642970 resolves a 28-residue RGG peptide with selected sc1 RNA and tests recognition-site mutants. The peptide contacts the duplex–quadruplex junction; the reported absence of intermolecular NOEs to the quadruplex segment does not negate binding to the structured RNA. Retain the original RNAcentral input. This establishes fragment-level recognition, not endogenous target occupancy or activity of every natural product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0002151 G-quadruplex RNA binding | EXP PMID:26374839 Crystal structure reveals specific recognition of a G-quadru... | ACCEPT | Summary: The RGG-region structural experiment supports G-quadruplex RNA binding. Reason: The original PMID:26374839 Methods/Results distinguish a synthetic human 527–544 R1A peptide in the crystal from separate 28-residue peptide binding and footprinting experiments. They support recognition of selected structured RNA, with the original RNAcentral input retained. They do not establish binding by every full-length natural product or the identity of an endogenous neuronal target. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0002151 G-quadruplex RNA binding | IDA PMID:18653529 The G-quartet containing FMRP binding site in FMR1 mRNA is a... | ACCEPT | Summary: FMRP recognizes G-quadruplex-containing RNA. Reason: The inspected binding experiments in PMID:18653529 compare GST-FMRP binding to the FMR1 N19 RNA and a structure-disrupting mutant; disrupting the G-quartets reduces specific binding. This is a directly supported RNA-recognition activity. The same paper found no detectable effect on FMR1 translation, stability or localization in the tested cells, so recognition alone does not imply repression of that transcript. Paper isoform labels are not assigned to UniProt products by number. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0002151 G-quadruplex RNA binding | IDA PMID:25464849 MOV10 and FMRP regulate AGO2 association with microRNA recog... | ACCEPT | Summary: G-quadruplex RNA recognition is supported by the sc1 comparison. Reason: The inspected PMID:25464849 Results explicitly compare FMRP and MOV10 binding to sc1 and a structure-disrupting mutant in Figure 3E. FMRP is a tested participant, despite MOV10 being the main focus. Preserve the distinction between this model-RNA experiment and endogenous MOV10 iCLIP or whole-brain complexes. Detailed supplementary construct methods were not inspected. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: RNA binding is a more informative description of this nucleic-acid-binding inference. Reason: The KH-domain mapping is consistent with nucleic-acid binding, but the experimentally established activity of FMRP is RNA recognition. Replace this very broad inference with RNA binding (GO:0003723), supported independently by the existing biochemical and cellular RNA-binding annotations; this does not infer a DNA-binding activity from the KH domain. Proposed replacements: RNA binding Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003682 chromatin binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chromatin association is retained as a specialized nuclear activity. Reason: This is an ISS transfer from mouse Fmr1, not a direct human assay. Independent PMID:24813610 experiments with Agenet-containing constructs, methylated histones and nucleosomes support a nuclear chromatin-binding role. Keep it distinct from the principal mRNA-regulatory function and from DNA-repair catalysis. Neither precise histone-site selectivity nor activity of every natural product follows from those constructs. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: Retain the experimentally curated RNA-binding annotation. Reason: PMID:22658674 reports a HeLa UV-crosslinking mRNA-interactome experiment. The FMRP-specific supplementary identification was not independently inspected, so the source-specific detection remains unverified. The annotation is retained by deferring to the experimental curator and the independently established RNA-binding function, not by assuming that every protein in the study was directly checked here. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: Retain the experimentally curated RNA-binding annotation. Reason: PMID:22681889 reports RNA crosslinking and poly(A)-RNA capture in human embryonic kidney cells. Its FMRP-specific identification was not independently inspected. RNA binding is independently established for FMRP, supporting retention of the function while leaving the precise high-throughput source assignment unverified. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | IDA PMID:15381419 The C terminus of fragile X mental retardation protein inter... | ACCEPT | Summary: Retain the established RNA-binding function while distinguishing the source-access limit. Reason: RNA binding is firmly established by independent FMRP biochemical and cellular experiments. The accessible PMID:15381419 abstract identifies the human 419–632 FMRP bait and RanBP9 interaction, but does not expose the precise RNA-binding assay used for this GOA assertion. Defer to the experimental curator for the source-specific assay; do not describe that assay as independently verified or reject it because the paper foregrounds a protein partner. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: RNA binding is a core activity supported beyond the domain inference. Reason: The InterPro KH and FMRP-family assignments are consistent with the existing direct RNA-binding and sequence-specific mRNA-binding experiments. Retain the broad RNA-binding function without interpreting a domain match as proof of one exclusive RNA motif or of equivalent activity in all alternative products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | IMP PMID:10496225 Dissecting FMR1, the protein responsible for fragile X syndr... | ACCEPT | Summary: RNA binding is experimentally supported for FMRP domains. Reason: The authentic PMID:10496225 abstract reports recombinant N-terminal, KH and C-terminal fragments and RNA homopolymer binding. It directly supports RNA interaction while documenting domain-dependent preferences. The isolated KH2 fragment was not stably folded under those conditions; that is not evidence that intact FMRP lacks KH2-dependent RNA recognition. Detailed full-text assay conditions were not inspected. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003723 RNA binding | TAS PMID:8156595 Essential role for KH domains in RNA binding: impaired RNA b... | ACCEPT | Summary: RNA recognition is a well-supported core molecular activity. Reason: The authentic PMID:8156595 abstract reports impaired RNA interaction for disease-associated KH-domain mutants, including I304N. This supports the RNA-binding function, alongside the existing direct mRNA-binding experiments. Full Methods and product-specific constructs were not inspected, and mutation effects are not interpreted as proving identical recognition by all natural products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | IDA PMID:11157796 Evidence that fragile X mental retardation protein is a nega... | ACCEPT | Summary: FMRP binds mRNA in the translation-repression experiments. Reason: The authentic PMID:11157796 abstract reports RNA-affinity measurements alongside translation repression in rabbit reticulocyte lysate and Xenopus oocytes; the I304N mutant does not simply lose all RNA affinity. Retain mRNA binding. Detailed protein construct/species and full assay methods were not inspected, so no natural-product assignment is inferred. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | IDA PMID:18936162 Fragile X mental retardation protein FMRP binds mRNAs in the... | ACCEPT | Summary: Retain mRNA binding in the nuclear-export-associated experiments. Reason: The authentic PMID:18936162 abstract reports RNA-dependent NXF1/FMRP complexes containing FMR1 mRNA, with engineered localization constructs in COS-7 cells and separate amphibian-oocyte experiments. These are not all native human-cell observations. mRNA interaction is independently established, supporting the curator’s assertion while leaving exact construct identity and directness of this source-specific interaction qualified. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | IDA PMID:25561520 Independent role for presynaptic FMRP revealed by an FMR1 mi... | ACCEPT | Summary: Human FMRP associates with target mRNAs in the reported cell assay. Reason: Original PMID:25561520 Results/Methods report tagged full-length human FMRP co-immunoprecipitating Map1b, Dlg4 and CamKIIa RNA in mouse cells. Keep that human-protein/heterologous-cell scope separate from the paper’s fly rescue and its human N-terminal fragment/BK-channel experiments. This supports mRNA association, not a claim that every tested channel effect is RNA dependent. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | IDA PMID:30765518 Phosphoregulated FMRP phase separation models activity-depen... | ACCEPT | Summary: RNA-dependent condensate assembly accompanies translation repression in vitro. Reason: PMID:30765518 uses recombinant human full-length and low-complexity-region constructs, model sc1 RNA and a separate luciferase-mRNA/rabbit-reticulocyte translation system. RNA promotes phase separation, and translation inhibition correlates with condensate formation. Retain the conjunctive original extension with this biochemical scope; it is not a direct endogenous-neuron experiment or proof that all repression uses condensates. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | UNDECIDED | Summary: mRNA binding is established; the complete signaling-adaptor extension remains undecided. Reason: The original PMID:31439799 main and supplementary experiments support FMRP-region RNA binding, CAPRIN1/FMRP condensate assembly and translation-related effects. The unresolved claim is the full source conjunction: this mRNA-binding activity is part of negative translation regulation and directly positively regulates signaling adaptor activity. The paper proposes integration of cellular signaling pathways through phosphorylation-sensitive condensates, but the inspected experiments do not settle that precise causal interpretation. This is not a negative judgment on mRNA binding, which is accepted in other source contexts. Preserve both extension atoms and retain UNDECIDED for the complete assertion rather than dropping the unresolved relation. |
| GO:0003729 mRNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: The family inference agrees with direct mRNA-binding evidence. Reason: The FMRP-family assignment supports mRNA binding and is corroborated by the gene’s existing direct mRNA binding, crosslinking and sequence-recognition experiments. Retain it as a core activity without turning the electronic inference into evidence for a particular endogenous transcript or natural product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003729 mRNA binding | TAS PMID:7692601 FMR1 protein: conserved RNP family domains and selective RNA... | ACCEPT | Summary: Direct binding to mRNA was reported in the foundational study. Reason: The authentic PMID:7692601 abstract reports FMRP binding to its own message and a subset of human fetal-brain mRNAs, including a measured affinity for the former. This supports the core mRNA-binding activity. The exact protein preparation and natural-product mapping were not established from the accessible abstract. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003730 mRNA 3'-UTR binding | IBA GO_REF:0000033 | ACCEPT | Summary: The curated phylogenetic inference supports conserved 3′-UTR recognition. Reason: The PTHR10603 target path places human FMRP below the actual PTN001318100 assertion node. Direct FMRP experiments, including PMID:17417632, independently support 3′-UTR binding. The human target appearing in the source set is valid descendant experimental grounding, not circularity, and donor count is not used to assess support. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003730 mRNA 3'-UTR binding | IDA PMID:17417632 A new function for the fragile X mental retardation protein ... | ACCEPT | Summary: Human FMRP directly binds a defined PSD-95 3′-UTR segment. Reason: Inspected PMID:17417632 Results use purified baculovirus-expressed human FMRP and fragments spanning the mouse PSD-95 3′-UTR; only fragment 5 binds, with competition and domain mapping. Mouse neuronal complexes are separate evidence. The tested G-rich site does not behave as a G-quartet, and binding does not by itself imply translational repression of PSD-95. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0003730 mRNA 3'-UTR binding | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic 3′-UTR-binding inference is independently supported. Reason: Direct binding to the PSD-95 3′-UTR in PMID:17417632 and human FMRP PAR-CLIP/biochemical work in PMID:23235829 support this specificity. Retain the ARBA inference without treating it as an additional independent experiment or claiming an exclusive 3′-UTR preference. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005515 protein binding | IPI PMID:10556305 A novel RNA-binding nuclear protein that interacts with the ... | KEEP AS NON CORE | Summary: NUFIP1 association is supported, with the original mouse-partner context retained. Reason: PMID:10556305 identifies NUFIP as an FMRP interactor by a two-hybrid screen and reports nuclear colocalization with an FMRP splice product. The curated Q9QXX8 partner is mouse Nufip1. The accessible abstract does not resolve the species of every experimental insert, so this source supports the reported interaction without a claim of independently audited cross-species construct identity. NUFIP1's RNA-binding activity is not a molecular function conferred on its protein partner. Retain this contextual interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:10556305 A novel RNA-binding nuclear protein that interacts with the ... | KEEP AS NON CORE | Summary: The human NUFIP1 partner annotation is retained with explicit primary-access limits. Reason: The NUFIP–FMRP interaction and nuclear colocalization described in PMID:10556305 support this curated association. The original Q9UHK0 partner identifies human NUFIP1; the abstract-only read does not independently verify the exact human construct used for this particular source context. Retain the experimentally curated interaction without inventing a native complex stoichiometry, an exclusive natural-product assignment, or a narrower binding class from NUFIP1's RNA-binding function. |
| GO:0005515 protein binding | IPI PMID:11157796 Evidence that fragile X mental retardation protein is a nega... | KEEP AS NON CORE | Summary: FMRP–FXR1 heteromeric association is supported. Reason: PMID:11157796 reports that the FMRP I304N mutation disrupts homooligomerization but does not reduce affinity for the related proteins FXR1 and FXR2. This is positive support for the FXR1 interaction, not evidence against it. Retain the generic association as non-core; the accessible abstract does not establish an exactly two-subunit native heterodimer or map the effect to every natural FMRP product. |
| GO:0005515 protein binding | IPI PMID:11157796 Evidence that fragile X mental retardation protein is a nega... | KEEP AS NON CORE | Summary: FMRP–FXR2 heteromeric association is supported. Reason: PMID:11157796 distinguishes altered I304N FMRP homooligomerization from preserved association with FXR2 and FXR1. Retain the FXR2 interaction as non-core. The reported heteromeric association does not by itself specify a native dimer stoichiometry or justify treating all natural FMRP products identically; no such extra claim is added. |
| GO:0005515 protein binding | IPI PMID:11438699 A highly conserved protein family interacting with the fragi... | KEEP AS NON CORE | Summary: FMRP association with CYFIP1 is supported. Reason: PMID:11438699 identifies CYFIP1 and CYFIP2 as FMRP-interacting proteins and maps binding to the FMRP N-terminal heteromerization region. The paper distinguishes CYFIP1 specificity for FMRP from CYFIP2 association with other FXR-family proteins. Retain the CYFIP1 interaction as non-core. CYFIP1's separate Rac1 interaction does not make this FMRP annotation a small-GTPase-binding assertion, and the interaction alone does not demonstrate a translation-initiation mechanism in every tested context. |
| GO:0005515 protein binding | IPI PMID:11438699 A highly conserved protein family interacting with the fragi... | KEEP AS NON CORE | Summary: FMRP association with CYFIP2 is supported. Reason: PMID:11438699 reports binding of CYFIP2 to FMRP and related FXR proteins, with the FMRP N-terminal region implicated. Retain the exact CYFIP2 partner context as non-core. Association with this regulatory protein does not transfer CYFIP2's other binding partners or biological activities to FMRP, and no native stoichiometry or all-product specificity is inferred from the accessible source. |
| GO:0005515 protein binding | IPI PMID:12837692 82-FIP, a novel FMRP (fragile X mental retardation protein) ... | KEEP AS NON CORE | Summary: The 82-FIP/NUFIP2 interaction is supported. Reason: PMID:12837692 identifies the protein later named NUFIP2 as an FMRP N-terminal interactor and describes its association with polyribosomal messenger ribonucleoprotein complexes. The abstract supports the curated interaction, while exact construct and species details beyond those stated remain unverified. Retain the binding context as non-core rather than infer a dedicated ribosome-binding or catalytic activity from membership in a larger ribonucleoprotein assembly. |
| GO:0005515 protein binding | IPI PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | KEEP AS NON CORE | Summary: RPLP0 association is supported in the tested I304N-FMRP context. Reason: PMID:15380484 reports coimmunoprecipitation of ribosomal protein P0 with inducibly expressed I304N-FMRP–EGFP in rat PC12 cells. This supports the reported interaction in that mutant, tagged cellular context. It does not establish purified binary affinity, contact with every ribosomal subunit, or an effect shared by all untagged wild-type FMRP products. Retain the source-specific protein association as non-core without replacing it solely from RPLP0's ribosomal identity. |
| GO:0005515 protein binding | IPI PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | KEEP AS NON CORE | Summary: FXR1 association persists in the tested I304N-FMRP complex. Reason: PMID:15380484 reports FXR1 coimmunoprecipitation with I304N-FMRP–EGFP in the inducible rat PC12 system. The mutation's abnormal granule behavior does not negate that association. Retain the contextual binding annotation; a mutant cellular complex is not proof of purified binary affinity, exact heterodimer stoichiometry, or a shared behavior of every natural FMRP product. |
| GO:0005515 protein binding | IPI PMID:15381419 The C terminus of fragile X mental retardation protein inter... | KEEP AS NON CORE | Summary: The FMRP C-terminal interaction with RANBP9 is supported. Reason: PMID:15381419 used the human FMRP C-terminal region, residues 419–632, as two-hybrid bait and identified interaction with the CRA region of RANBP9/RanBPM, with further in vitro and cellular confirmation reported in the abstract. Retain this partner-specific association as non-core. RANBP9's name and its own interaction network do not establish GTPase binding by FMRP, and this fragment assay does not map binding to every natural FMRP product. |
| GO:0005515 protein binding | IPI PMID:16407062 The structure of the N-terminal domain of the fragile X ment... | KEEP AS NON CORE | Summary: NUFIP2 binding to the N-terminal FMRP Tudor region is supported. Reason: PMID:16407062 combines structural characterization of the FMRP N-terminal region with binding analysis of 82-FIP/NUFIP2, implicating the second Tudor domain. Retain the original association as non-core. The Tudor fold does not alone establish recognition of a methylated amino acid or another modification-specific binding class. The two original source contexts project to one unchanged stored annotation and retain their separate provenance. |
| GO:0005515 protein binding | IPI PMID:16571602 The nuclear microspherule protein 58 is a novel RNA-binding ... | KEEP AS NON CORE | Summary: FMRP binds MSP58/MCRS1 in mapped fragment and cellular assays. Reason: Selected original Methods and Results in PMID:16571602 support interaction of the paper's human FMRP isoform 7 construct with MSP58/MCRS1. Yeast screening, nuclease-resistant reticulocyte/GST assays and cellular experiments implicate the FMRP region around residues 490–526. Retain the interaction as non-core. The paper's isoform numbering is not equated with a UniProt suffix; nucleolar recruitment of a separate overexpressed FMRP product does not establish all-product localization or a modification-specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:18093976 In vitro and in cellulo evidences for association of the sur... | KEEP AS NON CORE | Summary: SMN association is supported without making FMRP a constitutive SMN-complex subunit. Reason: PMID:18093976 provides cellular coimmunoprecipitation, reconstitution with an isolated SMN complex and nuclease-treated reticulocyte/GST binding evidence. The selected experiments distinguish human SH-SY5Y and HeLa material, mouse MN1 cells and tagged rat-neuron imaging. Mapping used the paper's 632-residue isoform 7 construct; that label is not a UniProt product assignment. Retain SMN protein binding as non-core without inferring a fixed core-SMN stoichiometry, snRNP-assembly catalysis or identical binding by every FMRP product. |
| GO:0005515 protein binding | IPI PMID:18936162 Fragile X mental retardation protein FMRP binds mRNAs in the... | KEEP AS NON CORE | Summary: RNA-dependent association with NXF1 is supported. Reason: PMID:18936162 reports RNA-dependent coimmunoprecipitation of FMRP and NXF1 in COS7 cells using EGFP-tagged FMRP and nuclear-localization/export variants. Retain the association in this ribonucleoprotein context as non-core. RNA dependence prevents interpreting the experiment as purified binary affinity; separate oocyte observations and engineered localization constructs do not establish a native human transport complex or an exclusive natural-product function. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | UNDECIDED | Summary: The source-specific FMRP–SFPQ pair remains unverified. Reason: PMID:21653829 describes a retested two-hybrid interaction network and validation of a subset in HEK293T cells, but the relevant Table S2 pair record was not recovered. The available main text and current target-specific IntAct query do not independently establish this exact SFPQ assay context. Keep the experimental assertion unresolved rather than infer a wrong partner or nonbinding. Independent SFPQ evidence from other papers does not verify which assay supported this particular source row. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | KEEP AS NON CORE | Summary: The reported FMRP–FXR1 network interaction is retained. Reason: PMID:21653829 explicitly describes the FMRP/FXR interaction network, consistent with the well-established FXR1 association. Retain the curated FXR1 interaction as non-core while acknowledging that its exact Table S2 entry was not recovered. The paper's HEK293T follow-up applies to a selected subset and is not asserted for this pair; a generic heteromeric interaction does not establish native dimer stoichiometry. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | KEEP AS NON CORE | Summary: The reported FMRP–FXR2 network interaction is retained. Reason: The FMRP/FXR network described in PMID:21653829 supports retaining this FXR2 association as non-core. Exact Table S2 pair details were not recovered, and global HEK293T validation of a subset is not assigned to this row. No exact heterodimer stoichiometry, native complex composition or product-specific affinity is inferred from the general interaction-network evidence. |
| GO:0005515 protein binding | IPI PMID:21771594 Evidence for the association of the human regulatory protein... | KEEP AS NON CORE | Summary: The FMRP–HABP4/Ki1-57 association is supported. Reason: PMID:21771594 reports immunoprecipitation evidence connecting human Ki1-57/HABP4 with FMRP in the context of translation-related ribonucleoproteins and stress granules. Retain this contextual association as non-core. The partner's localization and regulatory effects do not by themselves establish a narrower catalytic or binding activity for FMRP, and the accessible source does not resolve a purified binary interface or exact complex stoichiometry. |
| GO:0005515 protein binding | IPI PMID:24514761 Fragile X mental retardation protein stimulates ribonucleopr... | KEEP AS NON CORE | Summary: RNA-mediated association with influenza nucleoprotein is supported. Reason: PMID:24514761 reports FMRP association with influenza nucleoprotein in an RNA-mediated viral ribonucleoprotein context, with the FMRP KH2 I304N mutation disrupting the interaction. Retain the original viral-partner annotation as non-core. This evidence does not establish a purified binary nucleoprotein interface or make the infection-dependent association a constitutive function of every FMRP product. |
| GO:0005515 protein binding | IPI PMID:24658146 Subcellular fractionation and localization studies reveal a ... | KEEP AS NON CORE | Summary: Nucleolin association has both cellular and fragment-level support. Reason: Selected Results and Methods in PMID:24658146 show endogenous FMRP–nucleolin coimmunoprecipitation in HeLa cells that persists after RNase treatment, and fluorescence-polarization binding between the FMRP N-terminal region and a nucleolin RGG fragment. Full-length His-FMRP assays used bacterial lysate and are not described as purified full-length kinetics. Retain this specific interaction as non-core without transferring nucleolin's RNA-binding activity, claiming native dimer stoichiometry or assigning the fragment evidence to every natural product. |
| GO:0005515 protein binding | IPI PMID:24658146 Subcellular fractionation and localization studies reveal a ... | KEEP AS NON CORE | Summary: RNA-dependent CYFIP2 association is supported in HeLa cells. Reason: PMID:24658146 reports endogenous FMRP–CYFIP2 coimmunoprecipitation in HeLa cells with RNase sensitivity. Retain the association in its ribonucleoprotein context as non-core. This experiment is distinct from the paper's nucleolin fragment-binding measurements and does not establish purified binary CYFIP2 affinity or a universal association across all natural FMRP products. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | UNDECIDED | Summary: The precise FXR1 interaction in this large AP-MS source remains unverified. Reason: PMID:24981860 is an authentic study of tagged human-protein affinity purification and mass spectrometry, but the accessible abstract and publisher summary do not identify the exact FMRP–FXR1 experiment. The target-specific pair table was not recovered. Leave this source context unresolved rather than reject it because the paper foregrounds chromatin proteins. Independent FXR1 association is not a substitute for verifying this source-specific assay. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | UNDECIDED | Summary: The precise FXR2 interaction in this AP-MS source remains unverified. Reason: The authentic PMID:24981860 abstract supports a large human-protein affinity-purification study, but neither the accessible publisher summary nor the recovered target query supplies this exact FMRP–FXR2 pair record. Retain UNDECIDED for the source-specific claim. The chromatin emphasis is not evidence of wrong-gene attribution, and established FXR2 association elsewhere does not identify the experiment behind this row. |
| GO:0005515 protein binding | IPI PMID:25464849 MOV10 and FMRP regulate AGO2 association with microRNA recog... | MODIFY | Summary: Replace generic binding with enzyme binding for the experimentally supported MOV10 interaction. Reason: PMID:25464849 reports FMRP–MOV10 coimmunoprecipitation and RNase-treated association of recombinant proteins, supporting binding beyond partner co-occurrence. MOV10 is an RNA helicase/ATPase, so GO:0019899 enzyme binding is an informative replacement. The exact species of every purified insert was not independently established from the selected main text, whereas human HEK293T cellular evidence is explicit. MOV10 belongs to the DNA2/NAM7/SDE3 group; its helicase identity does not justify the narrower DEAD/H-box-helicase-binding term or helicase activity by FMRP. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | MODIFY | Summary: Replace generic binding with enzyme binding for ACOT7. Reason: PMID:26949739 identifies ACOT7 in the FMRP interactome of differentiated human SH-SY5Y cells and reports a targeted coimmunoprecipitation check with negative controls. ACOT7 is an acyl-CoA thioesterase, making GO:0019899 enzyme binding more informative than generic protein binding. Preserve the cellular association scope: this is not purified binary affinity, and association with ACOT7 does not give FMRP lipid-hydrolysis activity or establish the interaction in every neural cell type. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | KEEP AS NON CORE | Summary: FXR1 association is supported in the neuronal-cell interactome. Reason: PMID:26949739 explicitly reports recovery of FXR1 and FXR2 in the FMRP interactome from differentiated human SH-SY5Y cells. Retain the FXR1 association as non-core. The paper's targeted ACOT7 validation is not transferred to this pair, and the unreplayed supplementary pair table limits claims about individual scores, direct binary affinity and native heterodimer stoichiometry. |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | KEEP AS NON CORE | Summary: FXR2 association is supported in the neuronal-cell interactome. Reason: The selected primary text of PMID:26949739 names FXR2 among proteins recovered with FMRP in differentiated human SH-SY5Y cells. Retain the association as non-core while preserving the cellular AP-MS scope. No pair-specific ACOT7-style validation, purified affinity, exact dimer stoichiometry or universal neuronal occurrence is inferred for FXR2. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | KEEP AS NON CORE | Summary: The SFPQ interaction is supported by an exact fragment-screen record. Reason: The source-specific IntAct record for PMID:31413325 joins human FMRP and SFPQ in a yeast two-hybrid fragment-pooling assay, with the SFPQ sufficient-binding region recorded as residues 322–568. The aggregate FMRP bait information does not uniquely resolve one construct. Retain the experimentally supported interaction as non-core without turning fragment-screen binding into a native cellular complex, a defined dimer or an RNA-splicing activity of FMRP. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | KEEP AS NON CORE | Summary: The FXR1 interaction is supported by an exact fragment-screen record. Reason: For PMID:31413325, the exact human FMRP–FXR1 IntAct record reports yeast two-hybrid fragment pooling with FXR1 fragment regions and positive screen scores. The aggregate FMRP bait details do not isolate a unique native construct. Retain the association as non-core; fragment compatibility is not a measurement of full-length native heterodimer stoichiometry or an all-product binding claim. |
| GO:0005515 protein binding | IPI PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | KEEP AS NON CORE | Summary: The experimentally tested FMRP–CAPRIN1 association is supported. Reason: PMID:31439799 uses bacterially produced human FMRP residues 445–632 and CAPRIN1 residues 607–709 in biochemical condensate and translation assays. Retain the specific protein association as non-core, with phosphorylation and fragment context preserved. These constructs do not establish identical behavior of every full-length FMRP product. Deadenylation in the reconstituted system is performed by CNOT7, so it is not inferred as an enzymatic function of FMRP from this interaction. |
| GO:0005515 protein binding | IPI PMID:32525608 Novel FMRP interaction networks linked to cellular stress. | KEEP AS NON CORE | Summary: The primary table directly supports SFPQ association. Reason: PMID:32525608 Table 1 identifies SFPQ P23246 among human FMRP-fragment pull-down hits from HeLa lysate. Retain the association as non-core without claiming purified binary affinity. |
| GO:0005515 protein binding | IPI PMID:32525608 Novel FMRP interaction networks linked to cellular stress. | KEEP AS NON CORE | Summary: The source explicitly recovers FXR1 with FMRP. Reason: PMID:32525608 names FXR1 among recovered known interactors. Retain the fragment/HeLa-lysate association as non-core; native dimer stoichiometry and all-product binding were not established. |
| GO:0005515 protein binding | IPI PMID:32525608 Novel FMRP interaction networks linked to cellular stress. | KEEP AS NON CORE | Summary: G3BP1 association and the original stress-granule context are supported. Reason: PMID:32525608 supports cellular association and stress-granule colocalization; preserve occurs_in GO:0010494. Fragment mapping implicates G3BP1's proline-rich region, but cell-free specific binding was unresolved over GST controls. Retain non-core association without claiming an SH3-mediated interface. |
| GO:0005515 protein binding | IPI PMID:32525608 Novel FMRP interaction networks linked to cellular stress. | KEEP AS NON CORE | Summary: NUFIP2 is recovered in the source-specific interaction screen. Reason: PMID:32525608 explicitly names NUFIP2 among recovered known FMRP partners. Retain this fragment/lysate association as non-core, without purified binary affinity or product exclusivity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: FXR2 association is supported in two tagged cellular AP-MS contexts. Reason: Exact source-specific IntAct records for PMID:33961781 identify FXR2 bait and FMRP prey in anti-tag immunoprecipitation experiments in human HCT116 and HEK293T cells. Retain these cellular associations as non-core. The tandem-tagged bait experiments do not establish purified binary contact, native two-subunit stoichiometry or association of every endogenous FMRP product. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | UNDECIDED | Summary: The exact DYRK1A–FMRP assay requires source-specific confirmation. Reason: PMID:36950384 provides human induced-neuron interaction proteomics, but the selected main text and recovered target-specific IntAct response do not verify the exact DYRK1A–FMRP pair behind this annotation. An antibody listing is not pair validation, and no relevant supplementary pair record was recovered. Leave the interaction unresolved rather than remove it or promote it to protein-kinase binding solely from DYRK1A's catalytic identity. |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | MODIFY | Summary: Replace generic binding with transmembrane transporter binding for HCN1. Reason: The exact PMID:37207277 records include HCN1-bait association and a reverse FMRP-bait physical-association experiment in human induced neurons, with source locators for the validation data. HCN1 is an ion channel, fitting GO:0044325 transmembrane transporter binding, whose official narrow synonym is ion channel binding. Preserve the endogenous cellular immunoprecipitation scope; this does not demonstrate purified binary affinity, channel gating by FMRP or a shared interaction of all natural products. Proposed replacements: transmembrane transporter binding |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | MODIFY | Summary: Replace generic binding with GTPase activating protein binding for SYNGAP1. Reason: The PMID:37207277 source-specific records support SYNGAP1-bait association and a reverse FMRP-bait physical-association assay in human induced neurons. SYNGAP1 is a GTPase-activating protein, so GO:0032794 GTPase activating protein binding identifies the supported partner class. This preserves cellular complex evidence without assigning SYNGAP1's catalytic activity to FMRP, claiming purified binary affinity or assuming every natural FMRP product was tested. Proposed replacements: GTPase activating protein binding |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | UNDECIDED | Summary: The exact source records proximity, leaving protein binding unresolved. Reason: The PMID:39251607 IntAct record identifies an N-terminal BirA-tagged FXR2 bait and FMRP in a BioID proximity-labeling experiment in human K562 cells. Such proximity is compatible with association but does not by itself distinguish physical binding from shared local environment. Leave the inherited protein-binding assertion unresolved rather than claim biological nonbinding. HEK293T cells used for virus production are not the assay cell type, and the BioID record is not relabeled as coimmunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | UNDECIDED | Summary: The exact FXR2–FMRP modality and pair record remain unresolved. Reason: PMID:40205054 integrates several proteomic and structural modalities, including tagged-ORF affinity purification in human U2OS cells. The relevant FMRP–FXR2 pair record was not recovered from the selected main text or target-specific IntAct response. Do not assign a particular structural, cross-linking or binary assay from the overall study design. Preserve the original experimental annotation as UNDECIDED until the pair-specific supporting data can be checked. |
| GO:0005515 protein binding | IPI PMID:7489725 The fragile X mental retardation syndrome protein interacts ... | KEEP AS NON CORE | Summary: FXR1 heteromeric association is supported by the original family study. Reason: PMID:7489725 describes FMRP, FXR1 and FXR2 forming tight heteromeric and homomeric complexes in vivo and in vitro. Retain the FXR1 interaction as non-core. The accessible abstract does not establish an exactly two-subunit native heterodimer or distinguish every construct and natural product, so the generic association is retained without adding those stronger structural claims. |
| GO:0005515 protein binding | IPI PMID:7489725 The fragile X mental retardation syndrome protein interacts ... | KEEP AS NON CORE | Summary: FXR2 heteromeric association is supported by the original family study. Reason: The original PMID:7489725 abstract supports FMRP–FXR2 heteromeric association in cellular and in vitro contexts. Retain the interaction as non-core. The report of heteromers does not itself establish native dimer stoichiometry, purified affinity for every construct or exclusive binding by a particular natural FMRP product. |
| GO:0005634 nucleus | EXP PMID:10196376 Different targets for the fragile X-related proteins reveale... | KEEP AS NON CORE | Summary: Nuclear FMRP is supported in a nucleocytoplasmic-localization study. Reason: The PMID:10196376 abstract explicitly distinguishes FMRP nucleoplasmic shuttling from FXR2 nucleolar shuttling, including leptomycin-B/export-signal experiments and greater shuttling of I304N. Retain the nuclear assertion without transferring the paralog’s nucleolar targeting, asserting an unperturbed steady-state abundance, or assigning the same behavior to all products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | EXP PMID:16571602 The nuclear microspherule protein 58 is a novel RNA-binding ... | KEEP AS NON CORE | Summary: A nuclear FMRP splice construct occupies the nucleoplasm. Reason: Selected original PMID:16571602 Results/Methods show paper isoform 6 lacking exon 14/NES in the nucleoplasm when expressed alone, whereas paper isoform 7 remains cytoplasmic. MSP58 coexpression can recruit Iso 6 into nucleoli in COS-1; the paper reports related HeLa/STEK observations. Retain the nuclear/nucleoplasmic location contextually and distinguish overexpression from endogenous rat neural observations. Paper isoform labels are not inferred to equal UniProt numeric suffixes. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | EXP PMID:8789445 Alternative splicing of exon 14 determines nuclear or cytopl... | KEEP AS NON CORE | Summary: Exon 14-lacking FMRP splice forms show nuclear localization. Reason: PMID:8789445 explicitly reports nuclear immunofluorescence for transfected exon 14-excluding variants, while its subcellular fractionation did not show the same differential localization. Retain the product-dependent nuclear observation with that assay limitation. Current UniProt names/suffixes must be distinguished from the historical ISO names; no blanket nuclear assignment to all eleven products follows. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically supported nuclear localization is retained with product and state limits. Reason: The actual positive GO:0005634 IBD at PTN001318100 lies on the verified human FMR1 path in PTHR10603. Nuclear FMRP is supported independently by human localization/export studies, but nuclear abundance, splice product and experimental treatment matter. The IBA is not weakened by donor count or by human FMRP appearing among descendant evidence. Retain a contextual nuclear pool without assigning every current product the same distribution. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | IDA PMID:18936162 Fragile X mental retardation protein FMRP binds mRNAs in the... | KEEP AS NON CORE | Summary: Nuclear FMRP is supported in targeted export and RNA-association experiments. Reason: The authentic PMID:18936162 abstract describes EGFP-FMRP in COS-7, export-sequence/NLS manipulations, NXF1 knockdown, and RNA-dependent nuclear retention, with separate engineered construct/endogenous Xenopus chromosome observations. Retain nuclear localization with these perturbation and host limits. It does not establish constitutive nuclear residence of all human products or demonstrate the same nuclear itinerary under all conditions. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | IDA PMID:31753916 The RNA-binding protein FMRP facilitates the nuclear export ... | KEEP AS NON CORE | Summary: Nuclear FMRP is supported in the m6A-RNA export study. Reason: PMID:31753916 studies human HEK293T FMRP-associated RNA and FMR1-dependent nuclear/cytoplasmic RNA distribution. Selected original main Results and Methods were inspected; the main-text FMRP localization statements cite prior work, and the fractionation-control Figure S2 was not inspected. Retain the curator-supported nuclear assertion with independently established human nuclear FMRP observations (PMID:24204304 and PMID:16571602). Do not present the RNA distribution measurements as new image-based proof of FMRP localization, equate the mouse knockout cortex with human imaging, or assign every splice product constitutive nuclear residence. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The electronic nuclear-location mapping is supported but product dependent. Reason: The original ARBA/UniProt subcellular-location mapping agrees with experimental human nuclear FMRP observations. Preserve the electronic source fields and retain nuclear localization contextually, distinguishing the nuclear splice products and experimental treatment from the predominant cytoplasmic pool. A nuclear label alone does not establish chromatin, nucleolar or Cajal-body function for every product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rat-supported nuclear localization is retained as a contextual human inference. Reason: The exact donor Q80WE1 has a current experimental nuclear annotation from PMID:9030614, and the reviewed human record has independent nuclear observations. The existing ISS inference is biologically coherent. The rat experiment is not relabeled as a human experiment, and nuclear staining does not resolve every splice product or every nuclear subcompartment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005654 nucleoplasm | IDA PMID:16571602 The nuclear microspherule protein 58 is a novel RNA-binding ... | KEEP AS NON CORE | Summary: A nuclear FMRP splice construct occupies the nucleoplasm. Reason: Selected original PMID:16571602 Results/Methods show paper isoform 6 lacking exon 14/NES in the nucleoplasm when expressed alone, whereas paper isoform 7 remains cytoplasmic. MSP58 coexpression can recruit Iso 6 into nucleoli in COS-1; the paper reports related HeLa/STEK observations. Retain the nuclear/nucleoplasmic location contextually and distinguish overexpression from endogenous rat neural observations. Paper isoform labels are not inferred to equal UniProt numeric suffixes. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005654 nucleoplasm | TAS PMID:10888599 The fragile X-related proteins FXR1P and FXR2P contain a fun... | KEEP AS NON CORE | Summary: Nucleoplasmic FMRP is explicitly distinguished from paralog nucleolar targeting. Reason: The PMID:10888599 abstract explicitly states that prior FMRP localization was nucleoplasmic, while the main new nucleolar-targeting experiments concern FXR1/FXR2 isoforms. This is a legitimate traceable background assertion for the TAS nucleoplasm row, corroborated by PMID:16571602. Retain it contextually; do not transfer the paralogs’ nucleolar-targeting sequence or claim that FMRP was absent from the paper. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005694 chromosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Chromosome association is retained in replication-stress and meiotic contexts. Reason: The mouse donor P35922 carries the exact chromosome IDA from PMID:24813610. The actual primary evidence includes stress-enhanced chromatin association and meiotic chromosome context; the reviewed human UniProt location mapping derives from this evidence. Retain the contextual inference/electronic mapping without describing FMRP as a constitutive chromosome structural protein, a DNA-repair enzyme or universally chromosomal across products. Both original ISS contexts are preserved even though they share one exported seed row. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005694 chromosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chromosome association is retained in replication-stress and meiotic contexts. Reason: The mouse donor P35922 carries the exact chromosome IDA from PMID:24813610. The actual primary evidence includes stress-enhanced chromatin association and meiotic chromosome context; the reviewed human UniProt location mapping derives from this evidence. Retain the contextual inference/electronic mapping without describing FMRP as a constitutive chromosome structural protein, a DNA-repair enzyme or universally chromosomal across products. Both original ISS contexts are preserved even though they share one exported seed row. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005730 nucleolus | IDA PMID:16571602 The nuclear microspherule protein 58 is a novel RNA-binding ... | KEEP AS NON CORE | Summary: MSP58 coexpression recruits a nuclear FMRP construct to nucleoli. Reason: Selected original PMID:16571602 Results/Methods show paper isoform 6, which is nucleoplasmic alone, recruited to nucleoli after MSP58 coexpression in COS-1; paper isoform 7 remains cytoplasmic. The report also describes related HeLa/STEK observations. Retain this genuine contextual location, with overexpression and construct limits; do not reinterpret it as a universal endogenous human product distribution. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005730 nucleolus | IDA PMID:24658146 Subcellular fractionation and localization studies reveal a ... | KEEP AS NON CORE | Summary: Endogenous human FMRP has a nucleolar-associated pool. Reason: PMID:24658146 combines HeLa detergent-free fractionation and localization with evidence for approximately 200-kDa nucleolar FMRP complexes. Ordinary whole-cell nuclear/nucleolar staining is weak; artificial C-terminal fragments target nucleoli more strongly. Retain the endogenous contextual pool without transferring fragment behavior to all natural products or asserting a demonstrated nucleolar RNA-processing function. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A nucleolar FMRP pool is supported in defined cellular and product contexts. Reason: The UniProt nucleolar-location mapping is corroborated by endogenous human HeLa fractionation/localization in PMID:24658146 and the restricted nuclear construct experiments in PMID:16571602. Retain a contextual nucleolar pool without implying that all nuclear FMRP products reside there or that localization establishes ribosome-biogenesis activity. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005730 nucleolus | TAS PMID:16407062 The structure of the N-terminal domain of the fragile X ment... | KEEP AS NON CORE | Summary: The structural study supports a context-dependent nucleolar localization determinant. Reason: PMID:16407062 explicitly reports an N-terminal-domain fold associated with nucleolar localization and altered localization after fold destabilization. Its abstract does not provide full construct/cell or natural-product mapping. Retain the TAS location with independent human nucleolar corroboration; do not infer universal nucleolar residence, a catalytic role, or exact interface/product specificity from the structural abstract. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:10196376 Different targets for the fragile X-related proteins reveale... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is retained alongside regulated nuclear localization. Reason: PMID:10196376 explicitly reports cytoplasmic polyribosomal mRNP association and regulated nuclear shuttling of FMRP. Keep this broad experimentally supported pool without assuming that all cytoplasmic molecules are stress granules, that a particular splice product was uniquely responsible, or that nuclear perturbation results erase the cytoplasmic observation. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:12837692 82-FIP, a novel FMRP (fragile X mental retardation protein) ... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is retained in the 82-FIP interaction study. Reason: The authentic PMID:12837692 abstract identifies FMRP-containing polyribosomal mRNPs and contrasts FMRP localization with cell-cycle-dependent nuclear/cytoplasmic 82-FIP. Retain the broad cytoplasmic context. The partner’s cell-cycle behavior is not automatically assigned to FMRP, and exact product/compartment assays remain limited to the original curated claim. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:18664458 Tdrd3 is a novel stress granule-associated protein interacti... | KEEP AS NON CORE | Summary: The source supports a conditional cytoplasmic localization of endogenous FMRP. Reason: The PMID:18664458 abstract explicitly reports that TDRD3 overexpression induces stress granules and recruits endogenous FMRP into them. Retain the original cytoplasm assertion as non-core, with that induced stress-granule context stated explicitly. Induction does not invalidate the observed localization, but the experiment does not make stress granules the sole cytoplasmic pool, establish a constitutive basal distribution or test every natural product. Independent stress-granule annotations already retain the more specific compartment. |
| GO:0005737 cytoplasm | EXP PMID:24204304 Nuclear Fragile X Mental Retardation Protein is localized to... | MODIFY | Summary: Perinuclear cytoplasm captures a directly measured compartment in this study. Reason: PMID:24204304 directly distinguishes cytoplasmic/perinuclear FMRP from nuclear ISO6/12-related Cajal-body signals. Gentle in-situ lysis of HeLa cells leaves perinuclear FMRP granules outside the nucleus in a cytoskeletal framework (Results/Figure 2), while full-length GFP products remain cytoplasmic. Refine this broad source row to GO:0048471 perinuclear region of cytoplasm, already represented elsewhere. This refinement does not deny other cytoplasmic pools or transfer nuclear-product localization to the full-length products. Proposed replacements: perinuclear region of cytoplasm Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:7781595 FXR1, an autosomal homolog of the fragile X mental retardati... | KEEP AS NON CORE | Summary: The FXR1 paper explicitly includes cytoplasmic FMRP. Reason: The authentic PMID:7781595 abstract states that FMR1 and FXR1 proteins are cytoplasmic and can be coexpressed in the same cells, including human fragile-X comparison material. Retain the FMRP location; a title foregrounding FXR1 is not evidence of wrong-gene attribution. The abstract does not independently resolve a particular product or finer compartment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:8401578 The FMR-1 protein is cytoplasmic, most abundant in neurons a... | KEEP AS NON CORE | Summary: Human cytoplasmic FMRP is directly supported by tissue staining. Reason: PMID:8401578 reports specific antibodies, absent protein bands in affected full-mutation males, and cytoplasmic immunohistochemistry with strong neuronal expression. Retain the directly observed broad compartment, distinguishing tissue/cell differences and multiple detected bands from exact modern product identities. A separate cytosol assay cannot retroactively resolve all of these histological signals. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:8515814 Characterization and localization of the FMR-1 gene product ... | KEEP AS NON CORE | Summary: Cytoplasmic localization is supported with explicit cell and tissue limits. Reason: PMID:8515814 reports cytoplasmic localization after transient COS-1 expression and predominantly cytoplasmic epithelial staining, with some epithelial cells clearly nuclear. Multiple immunoblot products were detected but not mapped here to current accession suffixes. Retain the broad cytoplasmic observation without converting it into an exclusive localization or rejecting the nuclear minority. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | EXP PMID:8789445 Alternative splicing of exon 14 determines nuclear or cytopl... | KEEP AS NON CORE | Summary: Cytoplasmic splice products are retained separately from exon 14-excluding nuclear variants. Reason: PMID:8789445 compares transfected splice forms and reports nuclear immunofluorescence for exon 14-excluding variants, while conventional forms are cytoplasmic. Fractionation did not reproduce all imaging differences. Retain the cytoplasmic product context without assuming a paper ISO number equals the same current UniProt numeric suffix or that all products share one compartment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:15381419 The C terminus of fragile X mental retardation protein inter... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is retained without inferring a centrosomal location. Reason: PMID:15381419 describes FMRP as mainly cytoplasmic and assays a human 419–632 bait/interaction with RanBPM. The partner’s name does not locate FMRP at the microtubule-organizing center. Retain cytoplasm contextually, preserving the human fragment/whole-protein distinction and the lack of independently replayed finer localization from the abstract. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:16571602 The nuclear microspherule protein 58 is a novel RNA-binding ... | KEEP AS NON CORE | Summary: The cytoplasmic FMRP construct remains distinct from the nuclear splice construct. Reason: Selected original PMID:16571602 experiments show paper isoform 7 remaining cytoplasmic during MSP58 coexpression, unlike nuclear paper isoform 6. Endogenous neuronal co-localization was assessed in rat material. Retain the cytoplasmic context without assigning the paper’s isoform names directly to current UniProt suffixes or treating the rat observations as endogenous human imaging. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:18936162 Fragile X mental retardation protein FMRP binds mRNAs in the... | KEEP AS NON CORE | Summary: The cytoplasmic pool is retained in a study of experimentally perturbed nuclear export. Reason: PMID:18936162 contrasts cytoplasmic and nuclear distribution of engineered EGFP-FMRP under NLS/export-sequence and NXF1 perturbations in COS-7. Retain the broad cytoplasmic observation, without treating those engineered targeting experiments as a direct mapping to an endogenous human granule subtype or to all natural products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:19097999 Translational regulation of the human achaete-scute homologu... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is retained in the ASCL1 translation study. Reason: PMID:19097999 reports FMRP/hASH1 co-staining in newborn rat brain and FMRP-dependent translation/polysome redistribution in transfected human HEK293 cells. Full-length and naturally truncated proteins differ in reporter effects. Retain the broad cytoplasmic context while keeping rat tissue, human cell and product-function observations separate; no universal granular or nuclear location is inferred. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:25464849 MOV10 and FMRP regulate AGO2 association with microRNA recog... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is supported in polysomal RNA-regulatory complexes. Reason: Selected PMID:25464849 Results show FMRP/MOV10 in HEK293T and brain RNA-containing fractions and polysomes, with EDTA-sensitive sedimentation and partially RNA-dependent co-IP. Retain the broad cytoplasmic context; these actively translating complexes are not automatically equivalent to translationally silent stress granules. Detailed supplementary cell/product procedures were not replayed for every assay. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:25561520 Independent role for presynaptic FMRP revealed by an FMR1 mi... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is retained in translation and presynaptic-channel experiments. Reason: The original PMID:25561520 experiments include full-length N-terminally tagged human FMRP expressed in mouse cells and separate recombinant human 1–298 fragments tested against mouse-brain material/neurons. Retain the broad cytoplasmic location without assigning the fragment’s rapid physiological effect or the fly rescue experiment to every full-length human product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | KEEP AS NON CORE | Summary: The broad cytoplasmic location is retained without overstating the condensate model. Reason: PMID:31439799 directly examines minimal recombinant human FMRP 445–632/CAPRIN1 607–709 condensates and rabbit-reticulocyte translation. That is a mechanistic model, not imaging of all full-length products in human cytoplasm. The existing cytoplasmic assignment is independently well supported by human localization studies and is retained contextually; the paper-specific construct limitation remains explicit. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:9259278 Differential expression of FMR1, FXR1 and FXR2 proteins in h... | KEEP AS NON CORE | Summary: Cytoplasmic FMRP is observed in human tissue. Reason: The authentic PMID:9259278 abstract describes immunohistochemistry in human brain and testis and cytoplasmic coexpression of FMR1, FXR1 and FXR2 in selected differentiated neurons, with different fetal/tissue patterns. Retain this independently measured broad cellular pool. The abstract does not map the staining to a particular natural product or resolve it into one universal cytosolic/granule compartment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IDA PMID:9659908 FMRP associates with polyribosomes as an mRNP, and the I304N... | KEEP AS NON CORE | Summary: FMRP occupies cytoplasmic mRNP/polyribosomal pools. Reason: The PMID:9659908 abstract directly reports normal FMRP in large mRNP particles associated with elongating polyribosomes; I304N remains associated with cytoplasmic RNA but enters abnormal non-polysomal particles. Retain the broad cytoplasmic location and distinguish mutant from normal pools. These data do not reduce all cytoplasmic FMRP to one type of silent or stress granule. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The broad cytoplasmic mapping is retained across distinct FMRP pools. Reason: Reviewed UniProt localization and multiple human studies support cytoplasmic FMRP, including diffuse, polysomal, perinuclear and RNA-granule pools. Preserve this electronic broad-location assertion as contextual. A separate HPA cytosol call or one granule experiment does not establish that every independently observed cytoplasmic pool can be replaced by the same narrower location. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005737 cytoplasm | TAS PMID:16407062 The structure of the N-terminal domain of the fragile X ment... | KEEP AS NON CORE | Summary: The structural paper’s broad cytoplasmic context is retained. Reason: The TAS cytoplasm assertion is consistent with established human FMRP localization. PMID:16407062 primarily addresses the N-terminal domain and localization-sensitive folding; it does not justify assigning every cytoplasmic product to one granule subtype. Retain this broad contextual location, with independent human cytoplasmic evidence, rather than treating the nucleolar fragment/fold result as exclusion of the cytoplasmic pool. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: A cytosolic FMRP pool is consistent with its core RNA-regulatory activity. Reason: Preserve the original HPA or ARBA cytosol source assertion. Cytoplasmic RNA complexes and biochemical fractionation provide independent biological support for a cytosolic pool, but do not identify every product or abolish the separately supported nuclear, perinuclear and membrane-associated contexts. No HPA image or full ARBA rule replay is claimed here. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: A cytosolic FMRP pool is consistent with its core RNA-regulatory activity. Reason: Preserve the original HPA or ARBA cytosol source assertion. Cytoplasmic RNA complexes and biochemical fractionation provide independent biological support for a cytosolic pool, but do not identify every product or abolish the separately supported nuclear, perinuclear and membrane-associated contexts. No HPA image or full ARBA rule replay is claimed here. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: FMRP can associate with the plasma-membrane compartment in a channel-regulatory context. Reason: The reviewed human mapping/inference derives from mouse P35922; its exact current plasma-membrane experimental record cites PMID:24709664. The selected primary reading distinguishes mouse expression constructs, heterologous cells and rat neuronal assays. Retain contextual membrane association without asserting an integral transmembrane topology, endogenous human-neuron imaging, or identical localization of all products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP can associate with the plasma-membrane compartment in a channel-regulatory context. Reason: The reviewed human mapping/inference derives from mouse P35922; its exact current plasma-membrane experimental record cites PMID:24709664. The selected primary reading distinguishes mouse expression constructs, heterologous cells and rat neuronal assays. Retain contextual membrane association without asserting an integral transmembrane topology, endogenous human-neuron imaging, or identical localization of all products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0006281 DNA repair | IDA PMID:24813610 A chromatin-dependent role of the fragile X mental retardati... | KEEP AS NON CORE | Summary: FMRP contributes to chromatin-associated responses needed for repair after replication stress. Reason: PMID:24813610 combines endogenous human-cell depletion/rescue with mouse chromatin-binding mutants and meiotic analyses. Impaired BRCA1 recruitment and accumulated single-stranded intermediates support the repair-related annotation beyond localization alone. Retain it as a contextual function, with the repair chemistry performed by other proteins. The proposed docking mechanism remains incompletely defined, and an intact ionizing-radiation response in the tested knockout cells argues against a universal damage-response claim. |
| GO:0006281 DNA repair | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: A chromatin-associated DNA-damage-response role supports a contextual repair contribution. Reason: The ARBA inference is consistent with PMID:24813610. Human HeLa depletion/complementation and mouse experiments link FMRP chromatin binding to replication-stress responses, BRCA1 recruitment and unresolved repair intermediates. Retain a contextual contribution to DNA repair, distinct from the principal RNA-regulatory role. The experiments do not assign DNA-cleavage, synthesis or ligation activity to FMRP, nor a response to every kind of DNA damage. |
| GO:0006325 chromatin organization | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Chromatin-associated FMRP helps organize a damage-response context. Reason: This electronic inference originates from histone-H3 recognition. GO:0006325 includes organization of chromatin with associated proteins; PMID:24813610 connects FMRP chromatin binding to recruitment of damage-response proteins and processing of repair intermediates. Retain that contextual organization role rather than infer a general nucleosome-remodeling enzyme. Histone binding alone would not establish every form of chromatin organization, and the paper’s chromatin-accessibility/docking model is explicitly proposed. |
| GO:0006406 mRNA export from nucleus | IDA PMID:31753916 The RNA-binding protein FMRP facilitates the nuclear export ... | KEEP AS NON CORE | Summary: The original human-cell experiments support mRNA-export regulation. Reason: PMID:31753916 measures altered nuclear/cytoplasmic distribution after endogenous FMR1 depletion and uses nascent-RNA, transcription and decay controls. This supports a contextual export contribution, particularly for the examined methylated transcripts, rather than a pore-forming transporter. Mouse cortex is separate corroboration; the tagged construct is not assigned an unverified natural-product identity. The authors retain indirect and nuclear-decay possibilities for some targets. |
| GO:0006406 mRNA export from nucleus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FMRP can facilitate export of a subset of mRNAs from the nucleus. Reason: PMID:31753916 supports this ARBA inference through endogenous FMR1 depletion in human HEK293T cells, nuclear/cytoplasmic measurements and nascent-RNA experiments, with separate mouse-cortex data. Retain a nuclear RNA-trafficking role alongside the better-characterized cytoplasmic functions. The results do not establish a universal export receptor, direct nuclear-pore transport, or complete exclusion of nuclear-decay and indirect-target effects. |
| GO:0006417 regulation of translation | IEA GO_REF:0000002 | TOO GENERAL | Summary: More specific positive and negative translational-regulation annotations capture this function. Reason: FMRP is a genuine translational regulator, with target-dependent repression and activation. The InterPro-derived parent term is already represented by the retained GO:0017148 and GO:0045727 annotations, which are official descendants of GO:0006417. Mark this broad annotation as too general without denying regulation or forcing all RNA targets into one direction. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0007215 glutamate receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse evidence supports FMRP participation in glutamate-responsive RNA regulation. Reason: The original transfer points to mouse P35922. Current donor annotations include PMID:17417632 and PMID:18539120, linking glutamate-receptor stimulation to FMRP-dependent RNA stability and dendritic transport. These are downstream regulatory contributions, not glutamate-receptor activity of FMRP itself. Retain the conserved signaling-context annotation with neuronal and stimulus limits; the individual donor references do not all establish the same endpoint. |
| GO:0007215 glutamate receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The rat transfer is compatible with a glutamate-responsive regulatory role. Reason: The original donor is rat Q80WE1; PMID:9144248 reports rapid synaptic FMRP production after metabotropic-glutamate-receptor stimulation. That observation alone measures a response, not every downstream step performed by FMRP. Independent mouse RNA-stability and transport experiments provide the functional regulatory context. Retain this broader conserved pathway contribution without treating FMRP as the receptor or asserting an identical response in all neurons. |
| GO:0008017 microtubule binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse-donor microtubule association is supported. Reason: The exact mouse P35922 donor carries experimental support from PMID:18539120. Recovered original Results report nucleotide-dependent cosedimentation with taxol-stabilized microtubules; Methods use embryonic brain extracts. Retain the curated ISS as non-core, with extract association distinguished from purified binary affinity. The original GO_REF and donor are unchanged. |
| GO:0008143 poly(A) binding | IEP PMID:10496225 Dissecting FMR1, the protein responsible for fragile X syndr... | KEEP AS NON CORE | Summary: Poly(A) homopolymer interaction is retained as an assay-level binding property. Reason: The authentic PMID:10496225 abstract reports a recombinant C-terminal region that binds all four RNA homopolymers rather than a selective poly(A)-tail-recognition mechanism. Retain the original IEP evidence code and this binding property without making it a core physiological poly(A)-binding function. Full assay details were not inspected. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0008266 poly(U) RNA binding | IDA PMID:7688265 The protein product of the fragile X gene, FMR1, has charact... | UNDECIDED | Summary: The precise poly(U)-binding experiment remains unverified. Reason: The accessible PMID:7688265 abstract supports FMRP RNA binding in vitro but does not expose the poly(U)-specific assay. Other studies support RNA/homopolymer recognition, but they do not independently verify this exact source assertion. Leave the annotation undecided rather than infer a wrong-gene error or nonbinding from an incomplete abstract. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0008266 poly(U) RNA binding | IDA PMID:8156595 Essential role for KH domains in RNA binding: impaired RNA b... | UNDECIDED | Summary: The source-specific poly(U) assay could not be adjudicated. Reason: The authentic PMID:8156595 abstract establishes effects of KH mutations on RNA interaction, but the inspected material does not resolve the specific poly(U)-binding experiment. Preserve the curated experimental context as undecided; the general RNA-binding activity is accepted separately. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0008266 poly(U) RNA binding | IEP PMID:10496225 Dissecting FMR1, the protein responsible for fragile X syndr... | KEEP AS NON CORE | Summary: Poly(U) interaction is a supported biochemical property with domain-dependent specificity. Reason: PMID:10496225 reports RNA homopolymer assays on isolated FMRP domains, including nonselective C-terminal binding to the four bases. Retain this as non-core, with the original IEP code unchanged. It does not establish a specialized physiological poly(U) receptor or equivalence of all natural products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010369 chromocenter | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chromocenter association is supported under nuclear-export inhibition and replication stress. Reason: The exact mouse donor chromocenter IDA cites PMID:24813610. Actual Results describe FMRP foci near peri-centromeric chromocenters after leptomycin B, CENTB overlap and increased association following aphidicolin. Retain the human ISS inference contextually, without presenting it as an unperturbed constitutive nuclear compartment or a demonstrated kinetochore/repair catalytic role. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010494 cytoplasmic stress granule | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic stress granules are a supported FMRP RNA-regulatory compartment. Reason: The actual positive stress-granule IBD at PTN001318100 is on the verified human target path. Direct FMRP granule studies and endogenous FMRP recruitment into TDRD3-induced stress granules corroborate the biology. Retain this core RNA-granule localization without treating all basal FMRP particles as stress granules or using donor count as a confidence measure. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010494 cytoplasmic stress granule | IDA PMID:12417522 Trapping of messenger RNA by Fragile X Mental Retardation pr... | ACCEPT | Summary: FMRP is retained in cytoplasmic stress-granule assemblies. Reason: PMID:12417522 reports FMRP-containing RNA granules after transfection of the Fmr1-null STEK system, dynamic partitioning with polyribosomes, and translation repression. The accessible abstract describes granules reminiscent of stress granules; full assay/marker details were not independently recovered. The original curated assertion is retained with independent endogenous-FMRP stress-granule corroboration from PMID:18664458. This is not a claim that every neuronal RNP granule or natural product is constitutively stress-granular. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010494 cytoplasmic stress granule | IDA PMID:12417522 Trapping of messenger RNA by Fragile X Mental Retardation pr... | ACCEPT | Summary: FMRP is retained in cytoplasmic stress-granule assemblies. Reason: PMID:12417522 reports FMRP-containing RNA granules after transfection of the Fmr1-null STEK system, dynamic partitioning with polyribosomes, and translation repression. The accessible abstract describes granules reminiscent of stress granules; full assay/marker details were not independently recovered. The original curated assertion is retained with independent endogenous-FMRP stress-granule corroboration from PMID:18664458. This is not a claim that every neuronal RNP granule or natural product is constitutively stress-granular. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010494 cytoplasmic stress granule | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic stress-granule mapping is biologically supported. Reason: Preserve the original ARBA/UniProt source mapping. FMRP-containing RNA assemblies and recruitment of endogenous FMRP into TDRD3-induced stress granules support GO:0010494. This location is conditional on the granule/stress state, not a claim that every FMRP-containing mRNP particle is a stress granule. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0010646 regulation of cell communication | IEA GO_REF:0000117 | TOO GENERAL | Summary: Specific synaptic-transmission and action-potential annotations provide the useful coverage. Reason: The cell-communication parent is biologically compatible with FMRP’s neuronal regulatory roles, but it adds no distinct process specificity to the retained action-potential, synaptic-plasticity and neurotransmitter-secretion annotations. Official ancestry places those terms beneath regulation of cell communication. This is a specificity judgment, not a claim that the communication effects are false. |
| GO:0014069 postsynaptic density | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Postsynaptic-density localization is a supported rat-to-human contextual inference. Reason: The exact rat Q80WE1 donor has the postsynaptic-density IDA from PMID:9144248. Retain the curated human inference in the broader context of FMRP synaptic RNA regulation. The donor experiment was not independently recovered here, so no specific purification, residence time, endogenous human assay or all-product structural PSD role is claimed. The general dendritic/synaptic evidence does not make the source assertion false. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0015030 Cajal body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cajal-body localization is supported for restricted nuclear FMRP products. Reason: Actual PMID:24204304 Results/Methods show endogenous human FMRP-associated nuclear foci with coilin/SMN markers and fragile-X fibroblast controls, plus human ISO6/12 construct targeting. The tested mouse ISO6 variant lacks a 17-residue sequence and remains nucleoplasmic. Current UniProt links Cajal bodies to named isoforms 10/11 (Q06787-10/-11); that is curator-provided product correspondence, not an independent sequence replay here. Retain the location without assigning it to all eleven products or inferring snRNP-assembly function. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Membrane-associated recovery is retained with the proteomics limitation explicit. Reason: PMID:19946888 describes the YTS NK-like-cell membrane proteome and explicitly allows transiently associated non-integral proteins. The exact FMRP target table was not recovered in the abstract-only cache. Retain the curator-supported broad membrane context, consistent with independently observed FMRP membrane-associated/perinuclear fractions, without claiming a target-table replay, integral membrane insertion, or that this YTS signal specifically represents the neuronal plasma membrane. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0017148 negative regulation of translation | IDA PMID:12417522 Trapping of messenger RNA by Fragile X Mental Retardation pr... | ACCEPT | Summary: Translation repression is directly reported by the original transfection study. Reason: The authentic PMID:12417522 abstract reports repression of cotransfected reporters and RGG-dependent accumulation of RNA-containing granules in Fmr1-null STEK cells expressing FMRP. Although complete Methods were not recovered, this establishes the relevant core activity and agrees with independent human-protein reconstitution studies. Retain the curated direct annotation while keeping exact construct and granule-subtype limits explicit; no natural-product mapping is inferred. |
| GO:0017148 negative regulation of translation | IDA PMID:30765518 Phosphoregulated FMRP phase separation models activity-depen... | ACCEPT | Summary: Recombinant human FMRP low-complexity-region constructs repress translation in vitro. Reason: PMID:30765518 directly measures inhibition of luciferase-mRNA translation in rabbit-reticulocyte lysate after addition of human FMRP low-complexity-region protein. Inhibition correlates with RNA-containing condensate formation and shifts with phosphorylation or methylation. This supports the core repressive capacity, with a heterologous cell-free and artificial-fragment scope; correlation does not establish that every physiological repression mechanism requires phase separation. |
| GO:0017148 negative regulation of translation | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | ACCEPT | Summary: The FMRP–CAPRIN1 reconstitution supports translation repression. Reason: PMID:31439799 uses defined human FMRP and CAPRIN1 low-complexity-region constructs, RNA and translation-related reconstitution to connect phosphostate-dependent condensation with repression. Retain the core regulatory annotation with those construct and assay limits. CNOT7 is the catalytic deadenylase in the associated experiments; FMRP is not assigned that enzymatic activity, and the fragments are not treated as natural products. |
| GO:0017148 negative regulation of translation | NAS PMID:18805096 The fragile X syndrome protein represses activity-dependent ... | ACCEPT | Summary: FMRP-containing complexes repress translation through a CYFIP1-associated mechanism. Reason: PMID:18805096 supports translational repression involving FMRP and CYFIP1, with CYFIP1 supplying the demonstrated eIF4E interface. Retain the original NAS context as support for the core negative regulatory function. The accessible original selected Results and abstract do not justify assigning purified FMRP–eIF4E binding or assuming that this initiation mechanism explains all FMRP-dependent repression. |
| GO:0030371 translation repressor activity | IDA PMID:11157796 Evidence that fragile X mental retardation protein is a nega... | ACCEPT | Summary: FMRP represses translation in the reported cell-free and oocyte systems. Reason: The authentic PMID:11157796 abstract reports nanomolar inhibition of several mRNAs in rabbit reticulocyte lysate and Xenopus oocytes, with impaired repression by I304N. The suggested 80S-assembly mechanism was preliminary and should not be generalized into an exclusive mechanism. Exact construct/product details were not inspected. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030371 translation repressor activity | IEA GO_REF:0000117 | ACCEPT | Summary: Translation repression is supported independently of the electronic rule. Reason: Existing direct FMRP experiments in PMID:11157796 and recombinant human low-complexity-region experiments in PMID:30765518 support repression of translation. Retain the ARBA assertion as a core molecular activity while recognizing that FMRP can also promote translation of particular targets and that the mechanism is context dependent. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: Axonal FMRP localization supports its neuronal RNA-regulatory distribution. Reason: The exact mouse P35922 donor has axonal IDAs from PMID:16631377 and PMID:19193898; the reviewed human UniProt mapping retains this location. Preserve the original ISS/electronic source and accept the core compartment. These donor records establish curated experimental provenance, not a new direct human experiment, exact modern product mapping or a claim that FMRP is an axonal transport motor. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030424 axon | ISS GO_REF:0000024 | ACCEPT | Summary: Axonal FMRP localization supports its neuronal RNA-regulatory distribution. Reason: The exact mouse P35922 donor has axonal IDAs from PMID:16631377 and PMID:19193898; the reviewed human UniProt mapping retains this location. Preserve the original ISS/electronic source and accept the core compartment. These donor records establish curated experimental provenance, not a new direct human experiment, exact modern product mapping or a claim that FMRP is an axonal transport motor. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030425 dendrite | IEA GO_REF:0000044 | ACCEPT | Summary: Dendrites are a core compartment for FMRP RNA regulation. Reason: The exact mouse/rat donors have current experimental dendritic annotations, and the reviewed human record agrees with FMRP-containing RNA particles in neuronal processes. Retain the original ISS/electronic mapping, distinguishing donor experiments from direct human imaging and not assigning every splice product to dendrites. The more specific spine annotations describe a subset, not all dendritic FMRP. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030425 dendrite | ISS GO_REF:0000024 | ACCEPT | Summary: Dendrites are a core compartment for FMRP RNA regulation. Reason: The exact mouse/rat donors have current experimental dendritic annotations, and the reviewed human record agrees with FMRP-containing RNA particles in neuronal processes. Retain the original ISS/electronic mapping, distinguishing donor experiments from direct human imaging and not assigning every splice product to dendrites. The more specific spine annotations describe a subset, not all dendritic FMRP. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030425 dendrite | ISS GO_REF:0000024 | ACCEPT | Summary: Dendrites are a core compartment for FMRP RNA regulation. Reason: The exact mouse/rat donors have current experimental dendritic annotations, and the reviewed human record agrees with FMRP-containing RNA particles in neuronal processes. Retain the original ISS/electronic mapping, distinguishing donor experiments from direct human imaging and not assigning every splice product to dendrites. The more specific spine annotations describe a subset, not all dendritic FMRP. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030426 growth cone | IDA PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | ACCEPT | Summary: Growth-cone FMRP localization is retained with the neuronal-model limitation. Reason: The reviewed human location includes growth cones. PMID:15380484 uses inducible FMRP-I304N-EGFP in rat PC12 cells and contrasts the mutant’s diffuse neuritic distribution with normal FMRP granules; the accessible abstract does not replay the exact wild-type growth-cone panel or construct accession. The existing curated location is retained with independently coherent neuronal-granule localization, not rejected from the mutant-focused title and not relabeled as endogenous human growth-cone imaging. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0030426 growth cone | IEA GO_REF:0000120 | ACCEPT | Summary: Growth-cone FMRP localization is retained with the neuronal-model limitation. Reason: The reviewed human location includes growth cones. PMID:15380484 uses inducible FMRP-I304N-EGFP in rat PC12 cells and contrasts the mutant’s diffuse neuritic distribution with normal FMRP granules; the accessible abstract does not replay the exact wild-type growth-cone panel or construct accession. The existing curated location is retained with independently coherent neuronal-granule localization, not rejected from the mutant-focused title and not relabeled as endogenous human growth-cone imaging. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0031369 translation initiation factor binding | IPI PMID:24658146 Subcellular fractionation and localization studies reveal a ... | KEEP AS NON CORE | Summary: Retain the RNA-dependent association with translation initiation factor eIF5. Reason: Inspected PMID:24658146 Results/Methods show endogenous human HeLa FMRP co-immunoprecipitating eIF5; the association is lost after RNase treatment. Preserve the P55010/eIF5 partner and the observed association as non-core. This is not purified binary binding, an established initiation-factor regulatory mechanism, or eIF4E identification. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0032433 filopodium tip | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Filopodium-tip localization is retained as a neuronal-development context. Reason: The exact mouse P35922 donor carries a filopodium-tip IDA from PMID:16631377, also reflected in reviewed human UniProt localization. Retain this specific peripheral localization without claiming an independently replayed human tip assay, a motor/structural filopodial activity, or universal product targeting. It is a context of the broader neuronal RNA-granule biology. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0032433 filopodium tip | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Filopodium-tip localization is retained as a neuronal-development context. Reason: The exact mouse P35922 donor carries a filopodium-tip IDA from PMID:16631377, also reflected in reviewed human UniProt localization. Retain this specific peripheral localization without claiming an independently replayed human tip assay, a motor/structural filopodial activity, or universal product targeting. It is a context of the broader neuronal RNA-granule biology. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0032797 SMN complex | IDA PMID:18093976 In vitro and in cellulo evidences for association of the sur... | KEEP AS NON CORE | Summary: FMRP associates with the SMN complex in a restricted experimental context. Reason: PMID:18093976 supports FMRP–SMN association, including human SH-SY5Y tagged-FMRP co-IP, endogenous mouse MN1 co-IP, and partially overlapping tagged granules in rat hypothalamic neurons. Affinity-purified HeLa SMN complexes lacked detectable FMRP after stringent washing; recombinant FMRP could subsequently capture the complex. Retain the existing location/association assertion as contextual. These results do not establish a stoichiometric core SMN subunit, universal product membership, or FMRP participation in snRNP assembly. Paper iso 7 is not equated with the current UniProt suffix 7. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0033592 RNA strand annealing activity | IDA PMID:17057366 Dicer-derived microRNAs are utilized by the fragile X mental... | KEEP AS NON CORE | Summary: RNA strand annealing is directly measured as a biochemical activity. Reason: Inspected PMID:17057366 Methods/Results use recombinant FMRP, defined small RNAs and complementary target RNAs, remove protein before native-gel analysis, and include BSA and mismatched-target controls. Annealing is impaired by KH-domain deletion but retained by I304N. Keep this activity non-core pending its physiological contribution; it does not establish an obligatory universal role in RISC or an RNA-unwinding ATPase. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0034046 poly(G) binding | IDA PMID:7688265 The protein product of the fragile X gene, FMR1, has charact... | UNDECIDED | Summary: The exact poly(G)-binding assay is not independently verified. Reason: The accessible PMID:7688265 abstract supports RNA binding but does not specify the poly(G) experiment. Other FMRP studies support G-rich RNA recognition; they do not establish the exact assay or construct in this reference. Preserve the experimental assertion as undecided rather than infer its absence or falsity. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0034046 poly(G) binding | IEP PMID:10496225 Dissecting FMR1, the protein responsible for fragile X syndr... | KEEP AS NON CORE | Summary: Poly(G) binding reflects the tested domain preferences. Reason: The authentic PMID:10496225 abstract reports preferential poly(rG) interaction by recombinant N-terminal and KH1 regions and broader C-terminal homopolymer binding. Retain the biochemical specificity as non-core with the IEP code unchanged. Linear poly(G) binding is not automatically equivalent to G-quadruplex recognition. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0034063 cytoplasmic stress granule assembly | IDA PMID:12417522 Trapping of messenger RNA by Fragile X Mental Retardation pr... | KEEP AS NON CORE | Summary: FMRP contributes to stress-associated RNA-granule assembly. Reason: PMID:12417522 reports RGG-dependent RNA-containing granules after FMRP expression and describes their resemblance to stress granules; its complete marker/Methods details were not recovered. Independent PMID:19005212 reports stress-granule assembly defects in Fmr1-null fibroblasts and a human I304N cell line. Together these support a contextual assembly role while preserving the distinction between overexpression granules and endogenous stress responses. This is not a universal assignment to every natural product. |
| GO:0035197 siRNA binding | IDA PMID:17057366 Dicer-derived microRNAs are utilized by the fragile X mental... | KEEP AS NON CORE | Summary: FMRP interacts with siRNA substrates in the biochemical assays. Reason: PMID:17057366 directly examines siRNA species by EMSA and annealing assays. Mature single strands and their target pairing must be distinguished from the comparatively weak binding to a perfect siRNA duplex. Retain the binding activity as non-core; it does not establish that endogenous FMRP is universally required for RNA interference. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0035198 miRNA binding | IDA PMID:17057366 Dicer-derived microRNAs are utilized by the fragile X mental... | KEEP AS NON CORE | Summary: Binding of mature miRNA is directly supported in vitro. Reason: Inspected PMID:17057366 experiments incubate gel-purified Dicer products or defined mature miRNAs with recombinant FMRP and detect complexes by EMSA. Mature-miRNA binding is stronger than binding of the tested duplex species. Retain the measured non-core activity without extending it into a universal physiological silencing requirement. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0035198 miRNA binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: miRNA binding has direct biochemical support beyond the electronic inference. Reason: PMID:17057366 reports binding to mature miRNA and annealing with complementary target RNA. This supports the ARBA miRNA-binding inference as a biochemical property. Keep it non-core and do not infer obligatory mammalian RISC membership or equivalent binding to every miRNA. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0035591 signaling adaptor activity | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | UNDECIDED | Summary: Condensate scaffolding is established; the particular signaling-adaptor conjunction remains unresolved. Reason: PMID:31439799 directly studies human FMRP residues 445–632, CAPRIN1 residues 607–709 and RNA, demonstrating phosphorylation-sensitive interactions and condensates with translation and deadenylation readouts. These findings could connect cellular signals to RNA regulation; the main-text discussion presents integration of signaling pathways as a prediction. Whether the experiments establish the complete annotated conjunction—signaling adaptor activity with CAPRIN1 input, part of negative translation regulation, directly positively regulating condensate scaffold activity—remains uncertain. This does not show that signaling adaptor activity is absent, and a reconstituted experiment can in principle establish it. GO:0035591 and GO:0140693 are distinct sibling activities, so the established condensate result, already retained separately, is not an automatic descendant replacement. Preserve all three original extension atoms. CNOT7 performs the measured poly(A) cleavage; no deadenylase activity is assigned to FMRP. |
| GO:0035613 RNA stem-loop binding | IDA PMID:15805463 Kissing complex RNAs mediate interaction between the Fragile... | ACCEPT | Summary: Structured-RNA recognition by the KH region is supported. Reason: The authentic PMID:15805463 abstract identifies a KH2-recognized kissing-complex RNA structure and its relation to polyribosome association and I304N. This supports RNA stem-loop recognition as part of FMRP’s core RNA-binding repertoire. Detailed full-text construct and species provenance was not inspected, and the selected RNA does not define all endogenous targets. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0035613 RNA stem-loop binding | IDA PMID:19166269 A novel function for fragile X mental retardation protein in... | ACCEPT | Summary: FMRP recognizes the structured SoSLIP RNA element. Reason: Inspected PMID:19166269 Results describe recombinant FMRP/C-terminal binding to a 64-base Sod1 element that spans the start codon and forms three stem loops. Structure probing, competition and loop mutations support recognition distinct from G-quartets. Mouse neuronal and reporter results support target-specific positive translation; the exact recombinant product identity is not mapped to UniProt suffixes. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IDA PMID:15121898 The composition of Staufen-containing RNA granules from huma... | ACCEPT | Summary: Human FMRP is associated with cytoplasmic RNA granules in neuroblast-related experiments. Reason: PMID:15121898 describes human Staufen-containing complexes, FMRP verified among their components, and dendritic granule colocalization in differentiated human neuroblasts. The normal cache contains the abstract, Introduction and opening Discussion, not full Methods/Results; no uninspected panel is claimed. Preserve the original singleton part_of(CL:0000031 neuroblast) extension exactly. This supports the core RNP-granule compartment without claiming that every complex constituent directly binds FMRP. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IDA PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | ACCEPT | Summary: The original normal-FMRP RNP-granule assertion is retained alongside the mutant contrast. Reason: PMID:15380484 focuses on I304N-EGFP in rat PC12 cells, where visible granules are lost but neuritic movement remains. It explicitly contrasts normal FMRP granules, independently supported by PMID:12417734. Retain the curated normal-protein RNP-granule location; do not turn the mutant result into absence of wild-type granules or assume an unverified human construct/product identity. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IDA PMID:18093976 In vitro and in cellulo evidences for association of the sur... | ACCEPT | Summary: FMRP-containing cytoplasmic granules are directly observed in the SMN study’s neuronal model. Reason: The original PMID:18093976 reprint shows partially overlapping GFP-FMRP/SMN-RFP granules in somata and processes of rat hypothalamic neurons. Retain the core RNA-granule localization while separating tagged neuronal imaging from human SH-SY5Y biochemical assays. The tested paper isoform 7 natural-product/accession correspondence is unresolved; no stoichiometric SMN membership or universal product localization follows. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic RNP granules are a core FMRP compartment. Reason: The UniProt subcellular-location mapping is supported by FMRP RNA-particle studies, human Staufen-associated complexes and neuronal granule observations. Preserve the electronic source fields and accept the RNA-granule location without treating every active polyribosome or every stress condition as an identical particle type. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Presynaptic-membrane association is retained as a specific synaptic context. Reason: Mouse P35922 has current presynaptic-membrane experimental records from PMID:19193898 and PMID:27770568; reviewed human UniProt carries the corresponding inference/mapping. Retain the context without claiming integral membrane topology, independently replayed donor microscopy, or direct human all-product membrane localization. FMRP’s presynaptic activity and its RNA-granule pools remain distinct from being a constitutive membrane structural subunit. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042734 presynaptic membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Presynaptic-membrane association is retained as a specific synaptic context. Reason: Mouse P35922 has current presynaptic-membrane experimental records from PMID:19193898 and PMID:27770568; reviewed human UniProt carries the corresponding inference/mapping. Retain the context without claiming integral membrane topology, independently replayed donor microscopy, or direct human all-product membrane localization. FMRP’s presynaptic activity and its RNA-granule pools remain distinct from being a constitutive membrane structural subunit. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042802 identical protein binding | IDA PMID:11157796 Evidence that fragile X mental retardation protein is a nega... | KEEP AS NON CORE | Summary: Self-association is retained without assigning dimer stoichiometry. Reason: The authentic PMID:11157796 abstract reports impaired homo-oligomerization of I304N in relation to translation repression. This supports identical-protein association as a non-core property. It does not establish an obligatory native dimer, and exact construct and assay details remain limited by abstract-only access. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042802 identical protein binding | IPI PMID:17850748 Fragile X mental retardation syndrome: structure of the KH1-... | UNDECIDED | Summary: The source-specific self-association assay remains unresolved. Reason: The authentic PMID:17850748 abstract concerns structural and RNA-binding properties of human tandem KH domains. It does not independently resolve the self-association assertion, and the inspected IntAct response contains no record for this source. Neither fact demonstrates a curation error or nonbinding; retain the experimental row as undecided pending the relevant full-text assay. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042802 identical protein binding | IPI PMID:21446998 On the aggregation properties of FMRP--a link with the FXTAS... | UNDECIDED | Summary: Association under the studied folding conditions needs source-specific adjudication. Reason: The accessible PMID:21446998 abstract concerns folding, misfolding and aggregation of conserved human fragile-X-family fragments. The precise self-interaction experiment and its folded-versus-aggregated state were not inspected. An aggregation study should not be converted into a verified native FMRP assembly, nor rejected simply because of its focus; preserve this annotation as undecided. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042802 identical protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | KEEP AS NON CORE | Summary: The exact FMRP self-pair is supported in a fragment-pooling screen. Reason: The original IntAct record EBI-21375670 / IM-26801-3423 for PMID:31413325 joins human Q06787 to itself in a yeast two-hybrid fragment-pooling assay. The curator explicitly records an unresolved aggregate of bait constructs and prey sufficient-binding region 270–344. Retain this source-specific self-association as non-core without inferring full-length native binding, dimer stoichiometry or a particular natural product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0042803 protein homodimerization activity | IDA PMID:7489725 The fragile X mental retardation syndrome protein interacts ... | KEEP AS NON CORE | Summary: Retain the experimentally curated homodimerization activity. Reason: PMID:7489725 reports homomeric complexes in its authentic abstract. Independent dimerization evidence from PMID:12950170 and PMID:16636078 supports retaining this non-core activity. The original paper’s full assay was not independently inspected, and no all-product or fixed native-complex claim is added. |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Reported FMRP homodimerization is retained as non-core. Reason: PMID:12950170 reports stable dimers of the N-terminal 1–134 domain. PMID:16636078 independently assays FMRP self-capture and interprets it as homodimerization. These support the ARBA term with fragment and translation-lysate limits; a universal native stoichiometry is not asserted. |
| GO:0042995 cell projection | IDA PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | TOO GENERAL | Summary: Cell projection is broader than the neuronal processes relevant to this source. Reason: PMID:15380484 explicitly studies FMRP trafficking in differentiated rat PC12 neurites. GO:0042995 covers projections from many cell types; the retained neuron-projection and growth-cone annotations describe this neuronal-model setting more precisely. Official GO ancestry places neuron projection beneath cell projection. Mark the broad term as too general without changing the original source or claiming a direct human-neuron assay. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: Neuronal projections are a core compartment for FMRP-containing RNA particles. Reason: The GO:0043005 positive IBD at PTN000063980 is on the verified human FMR1 path. The inherited localization agrees with neuronal-process FMRP granules and reviewed axonal/dendritic localization. It does not depend on the number of extant donors and does not assign a motor activity to FMRP or claim identical distribution of all eleven products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043005 neuron projection | IDA PMID:18093976 In vitro and in cellulo evidences for association of the sur... | ACCEPT | Summary: FMRP-containing granules are observed in neuronal processes in the SMN study. Reason: PMID:18093976 directly images tagged FMRP/SMN granules in processes of rat hypothalamic neurons, with human biochemical assays reported separately. Retain neuron projection as a core location with the host/construct distinction; do not recast the imaging as endogenous human neurons or infer every natural product’s itinerary. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043005 neuron projection | IEA GO_REF:0000044 | ACCEPT | Summary: The electronic neuron-projection mapping matches core FMRP localization. Reason: Reviewed UniProt localization and FMRP-containing neuronal RNA particles support this mapping. Preserve the source fields and accept the compartment without assuming all neuronal projections contain the same molecular complex, all products are equivalent, or FMRP itself supplies microtubule motor activity. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043022 ribosome binding | IPI PMID:24658146 Subcellular fractionation and localization studies reveal a ... | ACCEPT | Summary: Ribosome association is supported in endogenous human protein complexes. Reason: Inspected PMID:24658146 Results/Methods show endogenous HeLa FMRP co-immunoprecipitating RPLP0, with the association persisting after RNase treatment, and high-molecular-weight translation-associated complexes. Retain ribosome binding as part of the translational regulatory mechanism. This source does not measure affinity of purified FMRP for isolated intact ribosomes or prove a binary RPLP0 interface. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043197 dendritic spine | IEA GO_REF:0000044 | ACCEPT | Summary: Dendritic spines are a supported compartment for FMRP synaptic RNA regulation. Reason: The exact mouse/rat donors have experimental dendritic-spine annotations, and the reviewed human location mapping agrees with FMRP’s synaptic RNA-regulatory role. Accept the existing ISS/electronic assertions while preserving donor and mapping provenance. No exact modern product correspondence, universal spine residence or direct human experiment is manufactured from the inference. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | ACCEPT | Summary: Dendritic spines are a supported compartment for FMRP synaptic RNA regulation. Reason: The exact mouse/rat donors have experimental dendritic-spine annotations, and the reviewed human location mapping agrees with FMRP’s synaptic RNA-regulatory role. Accept the existing ISS/electronic assertions while preserving donor and mapping provenance. No exact modern product correspondence, universal spine residence or direct human experiment is manufactured from the inference. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | ACCEPT | Summary: Dendritic spines are a supported compartment for FMRP synaptic RNA regulation. Reason: The exact mouse/rat donors have experimental dendritic-spine annotations, and the reviewed human location mapping agrees with FMRP’s synaptic RNA-regulatory role. Accept the existing ISS/electronic assertions while preserving donor and mapping provenance. No exact modern product correspondence, universal spine residence or direct human experiment is manufactured from the inference. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043204 perikaryon | EXP PMID:12417734 Transport of fragile X mental retardation protein via granul... | KEEP AS NON CORE | Summary: FMRP in the cell-body-to-neurite transport model is retained contextually. Reason: PMID:12417734 reports regulated FMRP-EGFP expression and RNA-containing granule trafficking in rat PC12 neurites. The reviewed perikaryon assertion fits the somatic starting pool, but the accessible abstract does not independently replay the exact soma panel or establish construct species/product identity. Retain the curated contextual location without turning this neuron-like-cell assay into endogenous human localization. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043204 perikaryon | IDA PMID:15380484 Transport kinetics of FMRP containing the I304N mutation of ... | KEEP AS NON CORE | Summary: The perikaryal FMRP context is retained without generalizing the I304N phenotype. Reason: PMID:15380484 compares mutant FMRP-I304N-EGFP trafficking with normal FMRP in rat PC12 cells. Preserve the curator-supported cell-body location while distinguishing loss of visible mutant granules from normal FMRP distribution. Exact construct/product and soma-panel details are not independently verified from the abstract. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043204 perikaryon | IDA PMID:18093976 In vitro and in cellulo evidences for association of the sur... | KEEP AS NON CORE | Summary: Somatic FMRP granules are observed in the rat neuronal model. Reason: PMID:18093976 images GFP-FMRP/SMN-RFP granules in the cell bodies of rat hypothalamic neurons. Retain the perikaryal context, separating tagged imaging from endogenous mouse co-IP and human biochemical assays. The source does not map every current human product or establish a dedicated somatic enzyme activity. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043204 perikaryon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Perikaryal localization is retained as a neuronal somatic context. Reason: The exact rat Q80WE1 donor has several experimental perikaryon records, including PMID:16571602, and the reviewed human record retains somatic FMRP granules. Preserve the original ISS/electronic source and retain this compartment contextually. Perikaryon specifies the neuronal soma excluding the nucleus; it does not establish a separate FMRP molecular activity or identical distribution of all products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perikaryal localization is retained as a neuronal somatic context. Reason: The exact rat Q80WE1 donor has several experimental perikaryon records, including PMID:16571602, and the reviewed human record retains somatic FMRP granules. Preserve the original ISS/electronic source and retain this compartment contextually. Perikaryon specifies the neuronal soma excluding the nucleus; it does not establish a separate FMRP molecular activity or identical distribution of all products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043232 intracellular membraneless organelle | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | TOO GENERAL | Summary: Intracellular membraneless organelle is broader than the supported FMRP RNP-granule localization. Reason: PMID:31439799 models human FMRP/CAPRIN1 RNA condensates using minimal disordered regions. GO:0043232 includes many unrelated structures, including chromosomes and the cytoskeleton. The existing cytoplasmic and neuronal RNP-granule annotations give the appropriate biological compartment; official GO ancestry places those granules beneath intracellular membraneless organelle. Mark this broad location as too general, without claiming direct human-neuron imaging or a separate new organelle function. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0043488 regulation of mRNA stability | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetic inference supports conserved regulation of mRNA stability. Reason: The actual PTHR10603 tree places human FMRP below the PTN001318100 assertion node, and the corresponding original IBD is present. Direct target-family evidence, including the PSD-95 experiments in PMID:17417632, supports RNA-stability regulation. Retain the inherited regulatory capacity rather than infer stabilization of every bound transcript. The validity of the ancestral judgment is not assessed by donor count. |
| GO:0043488 regulation of mRNA stability | ISS GO_REF:0000024 | ACCEPT | Summary: RNA-stability regulation is a supported part of FMRP’s post-transcriptional function. Reason: The ISS donor is mouse P35922. PMID:17417632 demonstrates FMRP-associated stabilization of PSD-95 mRNA in mouse neuronal systems, enhanced by metabotropic-glutamate-receptor activation; purified human FMRP separately recognizes the mouse RNA’s 3′ UTR. Retain the conserved stability-regulatory function, without turning binding alone into a universal stabilization effect. The same study distinguishes stability from FMRP-independent localization of this particular RNA. |
| GO:0043679 axon terminus | ISS GO_REF:0000024 | ACCEPT | Summary: Axon-terminal localization is a coherent core synaptic context. Reason: The exact rat Q80WE1 donor has an axon-terminus IDA from PMID:9030614, and reviewed human synaptic localization supports the inherited assertion. Retain it without claiming a newly replayed donor assay, direct human imaging, or all-product specificity. The presynaptic compartment is compatible with FMRP RNA regulation and independently documented presynaptic functions. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0044325 transmembrane transporter binding | IPI PMID:25561520 Independent role for presynaptic FMRP revealed by an FMR1 mi... | KEEP AS NON CORE | Summary: The tested interaction with the BK-channel complex is retained as non-core. Reason: Original PMID:25561520 uses a human FMRP N-terminal 1–298 construct in pull-downs with mouse brain BK-channel components, alongside acute neuronal rescue assays. Preserve the mouse beta4 partner Q9JIN6 and distinguish the lysate interaction from purified binary binding. These experiments support a translation-independent channel-associated role without assigning it to every natural product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0044830 host-mediated perturbation of viral RNA genome replication | IMP PMID:24514761 Fragile X mental retardation protein stimulates ribonucleopr... | KEEP AS NON CORE | Summary: FMRP promotes influenza ribonucleoprotein assembly and viral RNA production in tested cells. Reason: PMID:24514761 combines endogenous depletion in human cells, viral-RNP reconstitution and siRNA-resistant rescue. RNA-dependent NP association and assembly measurements support a host contribution that increases viral RNA production; the GO term permits promotion as well as inhibition. Retain this infection-context role, not a universal antiviral function or FMRP polymerase activity. Mouse infection and expression constructs remain separate evidence scopes. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: The complex-binding inference is correct but insufficiently informative. Reason: FMRP associates with several distinct ribonucleoprotein and protein assemblies. The generic ARBA macromolecular-complex-binding assertion does not identify which interface or activity is meant. Existing specific RNA, ribosome and partner annotations provide the functional detail; no single complex is invented as an exclusive replacement. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045182 translation regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved translation regulation is a core function. Reason: The actual PTHR10603 target path supports descent from PTN001318100 for this IBA. Human FMRP experiments support repression and target-dependent positive effects on translation, so the regulator term should not be narrowed to an exclusively negative effect. The source set is evaluated as a PAINT ancestral-node inference, not a vote by donor count or a circular self-transfer. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045202 synapse | IEA GO_REF:0000120 | ACCEPT | Summary: Synaptic localization is a core context spanning pre- and postsynaptic pools. Reason: The exact mouse P35922 synapse IDA cites PMID:16631377, with additional separate pre- and postsynaptic evidence in the reviewed record. Retain the existing ISS/electronic synapse assertion as the shared biological setting; do not erase it solely because distinct narrower subcompartments are also represented. Both original ISS contexts remain preserved through their shared exported seed row. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045202 synapse | ISS GO_REF:0000024 | ACCEPT | Summary: Synaptic localization is a core context spanning pre- and postsynaptic pools. Reason: The exact mouse P35922 synapse IDA cites PMID:16631377, with additional separate pre- and postsynaptic evidence in the reviewed record. Retain the existing ISS/electronic synapse assertion as the shared biological setting; do not erase it solely because distinct narrower subcompartments are also represented. Both original ISS contexts remain preserved through their shared exported seed row. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Postsynaptic-membrane association is retained as a defined synaptic context. Reason: The exact mouse P35922 donor carries postsynaptic-membrane records from PMID:19193898 and PMID:27770568, supporting the reviewed human inference/mapping. Retain the location contextually, without assigning integral membrane topology or an obligatory membrane structural role to FMRP. These donor records are not recast as independently inspected human assays or all-product localization. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Postsynaptic-membrane association is retained as a defined synaptic context. Reason: The exact mouse P35922 donor carries postsynaptic-membrane records from PMID:19193898 and PMID:27770568, supporting the reviewed human inference/mapping. Retain the location contextually, without assigning integral membrane topology or an obligatory membrane structural role to FMRP. These donor records are not recast as independently inspected human assays or all-product localization. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0045727 positive regulation of translation | IBA GO_REF:0000033 | ACCEPT | Summary: Positive translational regulation is a supported inherited capacity. Reason: The verified target path contains PTN001318100 and its positive-translation IBD. Human-target experiments in PMID:19097999 and additional RNA-specific work in PMID:19166269 establish activation for particular transcripts, alongside the well-established repressive capacity. Retain the ancestral positive-regulation assertion with target dependence. Human FMRP appearing among the descendant sources is legitimate experimental grounding, not circularity. |
| GO:0045727 positive regulation of translation | IDA PMID:19097999 Translational regulation of the human achaete-scute homologu... | ACCEPT | Summary: FMRP enhances hASH1/ASCL1 translation in the reported human-cell systems. Reason: Selected original PMID:19097999 Results show reduced ASCL1 protein after endogenous FMR1 silencing in human Kelly cells and increased hASH1 polysome association and UTR-reporter output in HEK293 experiments. RNA-level controls and U10-element deletion distinguish translational enhancement from increased reporter abundance. Retain this core regulatory capacity with RNA specificity; the tested shorter proteins did not reproduce the full-length effect, and no numeric natural-product equivalence is assumed. |
| GO:0045727 positive regulation of translation | IDA PMID:19166269 A novel function for fragile X mental retardation protein in... | ACCEPT | Summary: FMRP promotes translation mediated by the Sod1 stem-loop element. Reason: PMID:19166269 connects FMRP binding to the structured Sod1 element with reporter output and polysome association, while transcript-stability controls separate translation from RNA decay. Retain positive translational regulation with its RNA-specific scope. Mouse neuronal/STEK functional evidence and recombinant-fragment binding are distinguished, and old construct names are not mapped automatically to human natural-product suffixes. |
| GO:0045727 positive regulation of translation | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA positive-translation inference agrees with target-specific experiments. Reason: PMID:19097999 supports enhanced hASH1/ASCL1 translation and PMID:19166269 supports enhancement through the Sod1 RNA element. Retain positive translational regulation as one facet of the RNA-regulatory function. The effect depends on the RNA and tested construct; it does not contradict negative regulation of other transcripts or establish activation by every natural product. |
| GO:0045947 negative regulation of translational initiation | ISS GO_REF:0000024 | ACCEPT | Summary: FMRP can repress initiation through a CYFIP1-containing complex. Reason: The mouse P35922 transfer is grounded in the initiation-control mechanism reported in PMID:18805096. FMRP participates in a complex in which CYFIP1 engages eIF4E and limits initiation. Retain this mechanism within the core translational-regulatory function, without assigning CYFIP1’s measured interface to FMRP or claiming that elongation-associated and condensate-associated mechanisms are absent. |
| GO:0046928 regulation of neurotransmitter secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP regulates neurotransmitter release through presynaptic channel availability. Reason: The rat Q80WE1 donor is supported by PMID:24709664: FMRP depletion increases evoked exocytosis in rat neuronal preparations, and CaV2.2 blockade removes the difference. Retain contextual neurotransmitter-secretion regulation. The work separates endogenous rat-neuron effects from mouse FMRP expression in heterologous cells and does not establish the same response at every synapse or in every natural human product. |
| GO:0046982 protein heterodimerization activity | IDA PMID:7489725 The fragile X mental retardation syndrome protein interacts ... | KEEP AS NON CORE | Summary: Retain the experimentally curated heterodimerization activity. Reason: PMID:7489725 reports FMRP/FXR-family heteromeric complexes. The independently inspected PMID:16636078 heterodimerization assays corroborate the activity, supporting non-core retention while deferring to the original curator. The original paper’s full assay and exact native stoichiometry were not independently verified. |
| GO:0046982 protein heterodimerization activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Reported FXR-family heterodimerization is retained as non-core. Reason: PMID:16636078 explicitly assays FMRP–FXR1 capture as heterodimerization, supported by native HeLa association. Retain the ARBA inference as non-core with the translation-lysate and cellular-association scope stated; this does not independently measure purified complex stoichiometry or every natural product. |
| GO:0048027 mRNA 5'-UTR binding | IDA PMID:19166269 A novel function for fragile X mental retardation protein in... | ACCEPT | Summary: FMRP binds the 5′-UTR-containing SoSLIP region of Sod1 mRNA. Reason: Inspected PMID:19166269 Results map FMRP recognition to a 64-base sequence extending from 30 bases upstream to 34 bases downstream of the Sod1 start codon, with competition and structure-dependent binding. The site spans both UTR and coding sequence, so it is not wholly confined to the 5′ UTR. This does not invalidate binding within that region or imply a universal negative translational effect. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0048170 positive regulation of long-term neuronal synaptic plasticity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FMRP supports long-term plasticity in a stimulus-dependent neuronal context. Reason: The verified PTN000063980 IBD lies on the human target path. In the current rat evidence, PMID:28894415 finds reduced theta-burst LTP and low-frequency-stimulation LTD in knockout hippocampal slices, but enhanced chemically induced mGluR LTD. Retain positive regulation of long-term plasticity as a contextual inherited role rather than a uniform positive effect on every plasticity protocol. This term is broader than LTP alone. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:24658146 Subcellular fractionation and localization studies reveal a ... | KEEP AS NON CORE | Summary: Human endogenous FMRP has a perinuclear-associated pool. Reason: PMID:24658146 uses HeLa confocal localization and detergent-free fractionation to support perinuclear/ER-associated FMRP. Its heavy/light/nuclear-membrane fractions mix compartments; nuclear-membrane signal may reflect attached rough ER. Retain the directly observed perinuclear context without inventing integral membrane topology, ER-lumen targeting or a universal product localization. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The perinuclear-location mapping is supported by human-cell evidence. Reason: PMID:24658146 directly supports perinuclear/endoplasmic-reticulum-associated FMRP staining in HeLa and distinguishes mixed fractions from integral membrane topology. Retain the electronic perinuclear region context without converting it into a universal nuclear-envelope, ER-lumen or mitochondrial-matrix assignment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0048513 animal organ development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved RNA regulation contributes to animal-organ development. Reason: The actual tree and original IBD place the organ-development assertion at PTN001318100, above human FMRP. Retain the broad developmental contribution as non-core: FMRP’s RNA-regulatory work affects neuronal and other developmental programs, while this term does not identify its principal molecular mechanism. No target-specific evolutionary loss was demonstrated, and the number or identity of descendant donors is not treated as a reason to reject the ancestral judgment. |
| GO:0051028 mRNA transport | IBA GO_REF:0000033 | ACCEPT | Summary: The verified ancestral placement supports conserved mRNA transport. Reason: Human FMRP is below PTN001318100 in the actual tree and matches the target MSA sequence; the original mRNA-transport IBD is present. Independent neuronal-transport evidence and human nuclear-export experiments support RNA trafficking as part of its function. Retain the inherited capacity while separating nuclear export from dendritic transport and avoiding an untested universal cargo-adaptor mechanism. Self-inclusion among descendant evidence is not circular. |
| GO:0051028 mRNA transport | ISS GO_REF:0000024 | ACCEPT | Summary: FMRP participates in regulated mRNA transport. Reason: The mouse P35922 donor’s PMID:18539120 directly measures stimulus-dependent dendritic mRNA localization and particle movement; acute disruption of FMRP transport reduces target-RNA delivery. Retain this conserved RNA-trafficking function. Brain-extract motor association does not demonstrate motor catalysis or purified simultaneous RNA–motor bridging, and no uniform transport effect on every FMRP target is inferred. |
| GO:0051130 positive regulation of cellular component organization | IEA GO_REF:0000117 | UNDECIDED | Summary: The broad positive-direction organization inference needs a resolved specific endpoint. Reason: FMRP clearly regulates RNA condensates and neuronal morphology, but the original ARBA assertion adds a positive direction across cellular-component organization. The inspected donor morphology study does not cleanly distinguish protrusion assembly from persistence or maturation. Do not call this parent redundant with a positive filopodium child while that directional claim itself requires correction; leave the broad positive assertion unresolved rather than infer it from any structural phenotype. |
| GO:0051489 regulation of filopodium assembly | IDA PMID:16631377 Local functions for FMRP in axon growth cone motility and ac... | KEEP AS NON CORE | Summary: The cited neuronal study supports context-dependent filopodium regulation. Reason: The original PMID:16631377 abstract reports altered growth-cone motility, excess filopodia in knockout cultures and stimulus-dependent changes in wild-type cultures that are occluded in the knockout. These observations support regulation with developmental and activity dependence. Retain the curated assertion without inferring a single universal direction, a direct actin-assembly mechanism, or a particular natural-product identity from unavailable full Methods. |
| GO:0051489 regulation of filopodium assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FMRP regulates filopodial responses in developing neurons. Reason: The ARBA assertion agrees with PMID:16631377, which reports excess baseline filopodia and altered stimulus-dependent responses in Fmr1-deficient neuronal cultures. Retain the general regulatory role rather than force all developmental stages into one direction. This is a downstream morphological context of FMRP function, not direct actin-filament nucleation, and detailed construct/species assignment remains limited by access to the original abstract. |
| GO:0051491 positive regulation of filopodium assembly | ISS GO_REF:0000024 | MODIFY | Summary: The donor experiment supports filopodial regulation without a simple positive assembly direction. Reason: The original mouse source PMID:18539120 shows increased length and number of combined filopodia-spine protrusions when FMRP-dependent transport is disrupted. It cannot distinguish filopodia from spines, and maturation failure is a proposed explanation. Replace the positive assembly assertion with regulation of filopodium assembly, preserving the source and contextual effect without inferring a direct actin-assembly mechanism or assigning an opposite assembly rate from steady-state counts. Proposed replacements: regulation of filopodium assembly |
| GO:0060076 excitatory synapse | IDA PMID:18805096 The fragile X syndrome protein represses activity-dependent ... | ACCEPT | Summary: FMRP is retained in the excitatory-synapse translation-regulatory context. Reason: PMID:18805096 describes the FMRP–CYFIP1–eIF4E/BC1 translation-repression machinery and its response to BDNF or DHPG at neuronal synapses. Preserve the ComplexPortal-curated excitatory-synapse assertion, with the limitation that the abstract alone does not replay every localization panel, construct or species assignment. The supported synaptic regulatory context does not imply FMRP is a neurotransmitter receptor or a constitutive scaffold at every synapse. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0060965 negative regulation of miRNA-mediated gene silencing | IMP PMID:25464849 MOV10 and FMRP regulate AGO2 association with microRNA recog... | KEEP AS NON CORE | Summary: FMRP can protect selected RNAs from miRNA-mediated repression. Reason: PMID:25464849 shows that FMRP depletion increases AGO association and reduces expression of selected MAZ/WHSC1/USP22 reporters, whereas other targets behave differently. The binding-site arrangement with MOV10 helps explain this target dependence. Retain negative regulation of miRNA silencing as a contextual mechanism, without general inhibition of AGO or contradiction of FMRP-dependent positive silencing on other RNAs. |
| GO:0060998 regulation of dendritic spine development | IDA PMID:16631377 Local functions for FMRP in axon growth cone motility and ac... | KEEP AS NON CORE | Summary: The original study reports altered spine maturation and activity-dependent morphology. Reason: PMID:16631377 reports long/excess protrusions but fewer protrusions apposed to presynaptic terminals in deficient cultures, together with altered responses to depolarization. Retain regulation of dendritic-spine development with these endpoint limits. The original curated human annotation is not rejected because the accessible abstract emphasizes a knockout model, and unavailable construct details are not invented. |
| GO:0060998 regulation of dendritic spine development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FMRP regulates dendritic-spine development in a neuronal context. Reason: The ARBA assertion is consistent with PMID:16631377 and the transport-linked morphology study PMID:18539120. Retain context-dependent spine regulation as a developmental consequence of FMRP’s regulatory work. Spine number, length, synaptic apposition and activity-induced change are different endpoints; the annotation does not imply that FMRP directly builds the spine cytoskeleton or has one uniform effect across them. |
| GO:0060999 positive regulation of dendritic spine development | ISS GO_REF:0000024 | UNDECIDED | Summary: A positive effect on spine maturation is plausible but not resolved by the measured protrusion endpoint. Reason: The original mouse donor study PMID:18539120 measures more and longer combined filopodia-spine protrusions after FMRP-transport disruption; synapsin-positive puncta do not change. Its Discussion proposes persistence of immature protrusions. Leave this positive-development assertion undecided because the measured endpoint does not separately establish maturation, while retaining the broader spine-regulatory role. This uncertainty does not invalidate the actual transport or morphology effects. |
| GO:0070840 dynein complex binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse-donor dynein-complex association is supported. Reason: The exact mouse P35922 donor is supported by PMID:18539120. Original Results report coprecipitation with dynein, and Methods specify brain immunoprecipitation with dynein antibody and controls. Retain the contextual ISS as non-core; this is cellular-complex association, not purified motor affinity. The source’s emphasis on kinesin does not invalidate its dynein experiment. |
| GO:0071598 neuronal ribonucleoprotein granule | IDA PMID:30765518 Phosphoregulated FMRP phase separation models activity-depen... | ACCEPT | Summary: Neuronal RNP granules are retained as a core FMRP compartment, with model-system limits. Reason: PMID:30765518 assays recombinant human FMRP/LCR RNA droplets and translation in rabbit-reticulocyte lysate; its cell imaging uses overexpressed FMRP in CHO cells. It does not itself image endogenous human neuronal granules. Retain the clearly established neuronal-RNP location using the original curated assertion together with reviewed neuronal granule evidence and the matching mouse/rat experimental donor records, while preserving this paper-specific limit. No artificial LCR construct is assigned to every natural product. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0071598 neuronal ribonucleoprotein granule | IEA GO_REF:0000117 | ACCEPT | Summary: Neuronal RNP granules are a supported core compartment. Reason: The exact mouse P35922 donor has positive experimental neuronal-RNP-granule records, and the reviewed human mapping is consistent with FMRP RNA particles in neuronal processes. Accept the ISS/electronic location without converting donor assays into direct human experiments or extending an artificial LCR construct to every natural product. Distinguish these transport/regulatory particles from all stress granules and all translating polysomes. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0071598 neuronal ribonucleoprotein granule | ISS GO_REF:0000024 | ACCEPT | Summary: Neuronal RNP granules are a supported core compartment. Reason: The exact mouse P35922 donor has positive experimental neuronal-RNP-granule records, and the reviewed human mapping is consistent with FMRP RNA particles in neuronal processes. Accept the ISS/electronic location without converting donor assays into direct human experiments or extending an artificial LCR construct to every natural product. Distinguish these transport/regulatory particles from all stress granules and all translating polysomes. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0097386 glial cell projection | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Glial-cell projections are retained as a cell-type-specific localization context. Reason: The exact rat Q80WE1 donor carries a glial-cell-projection IDA from PMID:14613971, and the human record supports glial expression. Retain the curated inference contextually, with explicit rat-donor rather than independently observed human-process scope. Do not erase the glial pool because FMRP is best studied in neurons or infer a universal glial product/function from the location. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0098586 cellular response to virus | IDA PMID:24514761 Fragile X mental retardation protein stimulates ribonucleopr... | KEEP AS NON CORE | Summary: FMRP participates in the cellular response exploited by influenza infection. Reason: PMID:24514761 reports increased cellular FMRP during infection and target-specific effects of its depletion/rescue on viral RNP assembly and RNA production. Retain this infection-context response rather than an intrinsic universal antiviral program. The direction in these tested systems favors influenza replication, and observed association does not give FMRP a viral enzymatic activity. |
| GO:0098793 presynapse | ISS GO_REF:0000024 | ACCEPT | Summary: Both pre- and postsynaptic FMRP compartments are retained. Reason: Mouse P35922 has separate positive pre- and postsynapse IDAs from PMID:19193898; these correspond to the original human ISS contexts. Retain the core synaptic locations while preserving donor-specific evidence. This is not a claim that every pre- and postsynaptic effect uses an identical mechanism or that all eleven products occupy both compartments. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0098794 postsynapse | ISS GO_REF:0000024 | ACCEPT | Summary: Both pre- and postsynaptic FMRP compartments are retained. Reason: Mouse P35922 has separate positive pre- and postsynapse IDAs from PMID:19193898; these correspond to the original human ISS contexts. Retain the core synaptic locations while preserving donor-specific evidence. This is not a claim that every pre- and postsynaptic effect uses an identical mechanism or that all eleven products occupy both compartments. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0098908 regulation of neuronal action potential | IDA PMID:25561520 Independent role for presynaptic FMRP revealed by an FMR1 mi... | KEEP AS NON CORE | Summary: A translation-independent FMRP activity modulates neuronal action-potential width. Reason: PMID:25561520 reports rapid rescue of action-potential broadening in knockout mouse neurons by a purified human FMRP N-terminal construct, with loss of this effect for R138Q and supporting BK-channel association. Retain the neuronal excitability function with construct and species limits. This acute mechanism is distinct from RNA-dependent translational regulation and is not assigned to every natural product. |
| GO:0099577 regulation of translation at presynapse, modulating synaptic transmission | IBA GO_REF:0000033 | UNDECIDED | Summary: The specific presynaptic-translation mechanism needs additional source-level resolution. Reason: The actual PTN000063980 IBD and its position above human FMRP are verified. The current rat descendant annotations point to PMID:24709664, whose inspected experiments establish CaV2.2 surface/proteasomal regulation and exocytosis, not a direct measurement of translation at the presynapse. This source gap does not refute the PAINT curator’s broader ancestral judgment or establish evolutionary loss. Leave the combined translation-at-presynapse assertion undecided while retaining independently supported secretion regulation; neither donor count nor self-transfer is used as an objection. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000063980 · PTN000063980 UNRESOLVED The actual IBD and target descent are verified. The reviewed evidence does not yet settle the specific presynaptic-translation mechanism; no incorrect node placement or target-specific loss is asserted. RGD:2623 · rat Fmr1 UNRESOLVED Current descendant annotations point to PMID:24709664. Its inspected CaV2.2 surface/proteasomal regulation and exocytosis assays do not directly measure presynaptic translation; this gap does not refute the broader ancestral judgment. |
| GO:0140006 histone H3 reader activity | IDA PMID:24813610 A chromatin-dependent role of the fragile X mental retardati... | KEEP AS NON CORE | Summary: Histone recognition is retained as a specialized nuclear activity. Reason: The original PMID:24813610 main article and supplement support Agenet-containing FMRP constructs interacting with methylated H3/histones and nucleosomes, with human-cell and mouse-system experiments kept separate. This supports a non-core chromatin-reader role. Fragment assays do not establish an exclusive H3 modification-site specificity, catalytic DNA repair or equivalent activity in all natural products. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0140693 molecular condensate scaffold activity | EXP PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | ACCEPT | Summary: The FMRP low-complexity region contributes directly to condensate organization. Reason: Original PMID:31439799 main and supplementary experiments reconstitute the human FMRP 445–632 and CAPRIN1 607–709 regions with RNA and characterize phosphorylation-dependent phase behavior. The observed bringing together of macromolecules fits GO:0140693. It does not establish every full-length product’s behavior, a unique endogenous compartment or an FMRP-catalyzed deadenylation reaction. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0140693 molecular condensate scaffold activity | IDA PMID:30765518 Phosphoregulated FMRP phase separation models activity-depen... | ACCEPT | Summary: FMRP can scaffold RNA-containing condensates in the tested reconstituted system. Reason: Inspected PMID:30765518 Results compare recombinant human full-length protein, low-complexity-region deletion and isolated C-terminal region. RNA-dependent droplets, fusion/FRAP and recruitment of RNA/protein components support condensate scaffolding. The CHO overexpression and rabbit-reticulocyte translation experiments are distinct from endogenous neuronal granules; full physiological mechanism and natural-product scope remain limited. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0140693 molecular condensate scaffold activity | IPI PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | ACCEPT | Summary: The CAPRIN1-associated condensate-scaffold assertion has direct experimental support. Reason: PMID:31439799 directly examines FMRP-region/CAPRIN1-region/RNA assemblies in the original main and supplementary experiments. Preserve the CAPRIN1 Q14444 partner and the reconstituted fragment scope. Scaffold activity concerns organization of the condensate; CAPRIN1 interaction with CNOT7 and the latter enzyme’s catalysis must not be reassigned to FMRP. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:0140694 membraneless organelle assembly | IDA PMID:30765518 Phosphoregulated FMRP phase separation models activity-depen... | ACCEPT | Summary: FMRP provides RNA-dependent condensate-assembly capacity. Reason: PMID:30765518 directly shows dynamic RNA-containing droplets formed by human FMRP constructs and membrane-free foci after expression in CHO cells. The low-complexity region is an experimentally defined assembly determinant. Retain assembly as a mechanistic facet of the RNA-regulatory function, while distinguishing artificial fragments and overexpression from endogenous human neuronal organelles and avoiding a claim that every repression mechanism requires condensation. |
| GO:0140694 membraneless organelle assembly | IDA PMID:31439799 Phospho-dependent phase separation of FMRP and CAPRIN1 recap... | ACCEPT | Summary: FMRP and CAPRIN1 low-complexity regions assemble RNA-containing condensates. Reason: The original PMID:31439799 reconstitution and supplementary experiments support phosphostate-dependent assembly involving human FMRP and CAPRIN1 regions and RNA. Retain the original part_of negative-translation extension with that experimentally bounded assembly role. CNOT7 supplies catalytic deadenylation in the related assays; FMRP is an assembly participant, and the fragment results are not automatically assigned to all natural products. |
| GO:1900453 negative regulation of long-term synaptic depression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP limits a form of mGluR-dependent synaptic depression. Reason: The original transfer points to mouse P35922. The current donor’s PMID:11438589 is a developmental spine study and its exact LTD-supporting content was not independently resolved; it is not silently replaced. Separate original rat experiments in PMID:28894415 show enhanced DHPG-induced LTD after Fmr1 deletion, supporting the conserved contextual negative-regulatory role. The same rats have reduced low-frequency-stimulation LTD, so the direction is induction-specific rather than a universal suppression of LTD. |
| GO:1901254 positive regulation of intracellular transport of viral material | IMP PMID:24514761 Fragile X mental retardation protein stimulates ribonucleopr... | KEEP AS NON CORE | Summary: FMRP promotes efficient influenza-RNP export through its assembly contribution. Reason: PMID:24514761 shows nuclear retention of viral RNP components after endogenous FMRP depletion and rescue by wild-type but not the tested defective construct. Viral mRNA and NEP distributions are comparatively unchanged. Retain positive regulation of intracellular viral-material transport with the authors’ interpretation that impaired export follows defective RNP assembly; do not assign direct cargo-carrier or nuclear-export receptor activity to FMRP. |
| GO:1901386 negative regulation of voltage-gated calcium channel activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP reduces functional presynaptic CaV2.2 channel availability. Reason: The rat Q80WE1 donor is supported by PMID:24709664, which finds increased CaV-channel current after neuronal FMRP depletion and lower channel surface density upon expression. Single-channel gating and overall channel abundance are distinguished from surface availability. Retain negative regulation of voltage-gated calcium-channel activity through this contextual trafficking/proteostasis mechanism, without making FMRP a pore blocker or extending the effect to every calcium-channel subtype. |
| GO:1901800 positive regulation of proteasomal protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP promotes proteasome-dependent handling of CaV2.2 in the tested system. Reason: The mouse P35922 transfer is consistent with PMID:24709664, whose Methods identify a mouse FMRP expression template in the heterologous channel experiments. Proteasome inhibition reverses the surface-expression effect, supporting this specific proteostasis-regulatory role. Retain it as non-core rather than infer a universal protein-degradation regulator, E3 ligase or a demonstrated direct proteasomal-adaptor interface. |
| GO:1902737 dendritic filopodium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Developing neuronal filopodial compartments are retained contextually. Reason: The exact mouse/rat donors have experimental dendritic-filopodium or growth-cone-filopodium records (including PMID:16631377, PMID:18539120, PMID:15028757 and PMID:16098134 as appropriate to the unchanged source). Retain these fine localization contexts without claiming the donor primary panels were independently recovered, transferring them as direct human observations, or assigning FMRP a filopodial structural/motor function. Exact matching donor records are recorded in the source evidence. Selected original PMID:18539120 author-lab text was recovered through web extraction: mouse neuronal/brain transport, separate rat live imaging, and HEK293 construct experiments are distinguished. Filopodia versus spines were not separately resolved morphologically in that perturbation assay; its source-specific scope does not turn the other donor papers into inspected full text. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1902737 dendritic filopodium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Developing neuronal filopodial compartments are retained contextually. Reason: The exact mouse/rat donors have experimental dendritic-filopodium or growth-cone-filopodium records (including PMID:16631377, PMID:18539120, PMID:15028757 and PMID:16098134 as appropriate to the unchanged source). Retain these fine localization contexts without claiming the donor primary panels were independently recovered, transferring them as direct human observations, or assigning FMRP a filopodial structural/motor function. Exact matching donor records are recorded in the source evidence. Selected original PMID:18539120 author-lab text was recovered through web extraction: mouse neuronal/brain transport, separate rat live imaging, and HEK293 construct experiments are distinguished. Filopodia versus spines were not separately resolved morphologically in that perturbation assay; its source-specific scope does not turn the other donor papers into inspected full text. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1903311 regulation of mRNA metabolic process | NAS PMID:32878499 Fragile X-related protein family: a double-edged sword in ne... | TOO GENERAL | Summary: Specific RNA-stability and splicing annotations provide the relevant coverage. Reason: PMID:32878499 is a review-level synthesis of fragile-X-family RNA functions. The broad mRNA-metabolism regulation term encompasses the more specific retained stability and alternative-splicing regulatory annotations by official ontology ancestry. Mark it as too general without denying those processes or treating a secondary synthesis as an additional direct experiment. |
| GO:1903502 translation repressor complex | IPI PMID:18805096 The fragile X syndrome protein represses activity-dependent ... | ACCEPT | Summary: FMRP participates in a translation-repressor protein complex. Reason: PMID:18805096 explicitly describes FMRP association with the CYFIP1–eIF4E/BC1 regulatory machinery and activity-dependent release of repression. This supports the existing translation repressor complex assertion as a core context. CYFIP1 supplies the described direct eIF4E contact; complex participation does not require FMRP to possess that same interface or to be an enzymatic catalyst. The abstract-level source boundary does not invalidate the well-established complex assignment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990247 N6-methyladenosine-containing RNA reader activity | IDA PMID:31753916 The RNA-binding protein FMRP facilitates the nuclear export ... | KEEP AS NON CORE | Summary: Retain m6A-associated RNA recognition with the original assay limitations. Reason: Original PMID:31753916 selected Results/Methods use FLAG-HA FMRP in HEK293T PAR-CLIP and anti-m6A enrichment; I304N reduces general RNA binding. Separate PMID:28869609 assays support sequence-dependent preferential recovery of methylated RNA using recombinant GST-FMRP in bacterial extracts. These observations support a contextual reader role without a purified matched-affinity measurement in the original paper, proof of direct atomic m6A recognition, or product-specific assignment. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990247 N6-methyladenosine-containing RNA reader activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: m6A-containing RNA recognition is supported with biochemical context limits. Reason: The ARBA inference is corroborated by PMID:31753916 cellular crosslinking/methylated-RNA analyses and PMID:28869609 matched methylated/unmethylated RNA pull-downs. The latter uses recombinant GST-FMRP in clarified bacterial extracts, not inspected purified binary affinity measurements. Retain the reader function as non-core, without claiming a universal sequence-independent m6A sensor or methylation-specificity of I304N. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990812 growth cone filopodium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Developing neuronal filopodial compartments are retained contextually. Reason: The exact mouse/rat donors have experimental dendritic-filopodium or growth-cone-filopodium records (including PMID:16631377, PMID:18539120, PMID:15028757 and PMID:16098134 as appropriate to the unchanged source). Retain these fine localization contexts without claiming the donor primary panels were independently recovered, transferring them as direct human observations, or assigning FMRP a filopodial structural/motor function. Exact matching donor records are recorded in the source evidence. Selected original PMID:18539120 author-lab text was recovered through web extraction: mouse neuronal/brain transport, separate rat live imaging, and HEK293 construct experiments are distinguished. Filopodia versus spines were not separately resolved morphologically in that perturbation assay; its source-specific scope does not turn the other donor papers into inspected full text. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990825 sequence-specific mRNA binding | IDA PMID:12927206 The fragile X mental retardation protein binds and regulates... | ACCEPT | Summary: Sequence-selective mRNA recognition is a core molecular activity. Reason: The authentic PMID:12927206 abstract reports cDNA-SELEX identification of human U-rich mRNA targets, with separate mouse-brain expression studies. This supports selective RNA recognition without equating target expression changes to direct binding in vivo. Exact protein construct details were not inspected; independent PMID:23235829 experiments strengthen the general sequence-specific function. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990825 sequence-specific mRNA binding | IDA PMID:23235829 FMRP targets distinct mRNA sequence elements to regulate pro... | ACCEPT | Summary: Human FMRP shows experimentally established sequence-dependent mRNA recognition. Reason: Inspected PMID:23235829 Results combine human HEK293 FLAG-HA FMRP PAR-CLIP with Sf9-purified recombinant protein EMSAs, sequence variants and I304N analysis. ACUK and WGGA enrichment and differing affinities support specificity, while RNA length and multiple recognition elements influence binding. Paper isoforms 1 and 7 are not equated to UniProt suffixes, and a HEK293 target list is not automatically a neuronal target catalogue. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:1990904 ribonucleoprotein complex | IDA PMID:9659908 FMRP associates with polyribosomes as an mRNP, and the I304N... | ACCEPT | Summary: FMRP is a core component of RNA-containing regulatory particles. Reason: PMID:9659908 directly reports FMRP in large mRNP particles associated with elongating polyribosomes and separates the altered particles made by I304N. Retain the ribonucleoprotein-complex assertion as a core physical setting for RNA regulation. It does not require all particles to be neuronal transport granules or stress granules, and no ribosomal-subunit identity or autonomous catalytic activity is inferred. Supporting Evidence: file:human/FMR1/FMR1-source-guide.md |
| GO:2000301 negative regulation of synaptic vesicle exocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: FMRP restrains evoked synaptic-vesicle exocytosis in the rat neuronal assay. Reason: PMID:24709664 directly connects FMRP depletion to increased evoked exocytosis in rat neuronal cultures and shows loss of that difference after CaV2.2 blockade. Retain this specific donor-supported output with its preparation and stimulation limits. The mechanism is linked to channel availability; it does not establish presynaptic translation as the measured causal step or uniform inhibition at all synapses. |
| GO:2000637 positive regulation of miRNA-mediated gene silencing | IDA PMID:17057366 Dicer-derived microRNAs are utilized by the fragile X mental... | KEEP AS NON CORE | Summary: FMRP can enhance short-RNA-mediated silencing in particular assay contexts. Reason: PMID:17057366 provides biochemical RNA-annealing evidence and a reduced reporter-silencing response in the tested Fmr1-deficient fibroblasts. PMID:19005212 reports preserved silencing in other tested fibroblast reporters, so FMRP should not be described as universally required for RISC. Retain the positive regulation with target/assay dependence rather than erase the original observations or infer miRNA cleavage by FMRP. The complementary negative effects in PMID:25464849 are likewise target-dependent. |
| GO:2000766 negative regulation of cytoplasmic translation | ISS GO_REF:0000024 | ACCEPT | Summary: Conserved cytoplasmic translation repression is experimentally supported. Reason: The mouse P35922 donor is supported by PMID:11376146, whose authentic abstract reports purified recombinant FMRP inhibition of translation in rabbit-reticulocyte lysate, RNA-binding dependence and no accelerated mRNA degradation. Human FMRP reconstitution in PMID:30765518 supplies independent direct support. Retain the core negative-regulatory capacity while preserving the distinction between the donor assay and human constructs and avoiding unverified natural-product assignments. |
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Download this section (compressed HTML)Q: Which modern FMRP products account for the nuclear, nucleolar and neuronal RNA-granule observations, after historical isoform names are aligned to exact sequences?
Q: Which RNA features and partner or modification states determine whether FMRP represses translation, promotes translation, or stabilizes a target transcript?
Q: Does the unresolved presynaptic-translation IBA reflect direct local translation control in the relevant compartment, independently of the established translation-independent channel and exocytosis effects?
Q: Which components mediate FMRP association with microtubules and dynein, and which interactions are direct rather than bridged within ribonucleoprotein particles?
Experiment: Compare sequence-verified natural FMRP products at endogenous expression in matched human neuronal and non-neuronal cells, combining localization with target-resolved RNA binding, transport, stability and translation measurements.
Experiment: Measure local presynaptic translation and rapid channel/exocytosis responses separately after acute FMRP perturbation, using RNA-binding and channel-association separation-of-function constructs whose sequences are reported.
Experiment: Reconstitute FMRP–RNA–motor assemblies with defined components and compare their transport behavior with endogenous particles, separating direct contacts from lysate-dependent associations.
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