TRA2B is an SR-like nuclear splicing regulator whose central RNA-recognition motif binds AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Through its arginine/serine-rich regions and interactions with other splicing factors, it couples bound exonic elements to spliceosomal machinery and controls exon selection, promoting or repressing inclusion according to RNA and partner context. Established targets include MAPT, SMN2, CHEK1, AGER, and the TRA2B poison exon that mediates negative autoregulation; TRA2A compensates for TRA2B at many endogenous targets.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0000398 mRNA splicing, via spliceosome | IBA GO_REF:0000033 | MODIFY | Summary: The family-level annotation correctly places TRA2B in spliceosomal mRNA splicing, but describes it as core machinery rather than as a regulator of splice-site choice. Reason: TRA2B regulates both constitutive and alternative target exons, so the general regulatory parent GO:0048024 is more accurate here than the alternative-only child. It also avoids implying that TRA2B performs the core splicing reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION GRANULARITY MISMATCH Proposed replacements: regulation of mRNA splicing, via spliceosome Supporting Evidence: PMID:25208576 Here we find simultaneous--but not individual--depletion of Tra2Ξ± and Tra2Ξ² induces substantial shifts in splicing of endogenous Tra2Ξ² target exons, and that both constitutive and alternative target exons are under dual Tra2Ξ±-Tra2Ξ² control. |
| GO:0005681 spliceosomal complex | IBA GO_REF:0000033 | ACCEPT | Summary: Spliceosomal-complex association is consistent with phylogenetic, experimental, and pathway evidence and with TRA2B coupling enhancer-bound RNA to snRNP machinery. Reason: TRA2B functions in dynamic pre-mRNA processing assemblies, and independent mechanistic evidence connects ESE-bound TRA2 proteins to U1/U2 spliceosomal machinery. Supporting Evidence: PMID:10339552 The results suggest a model for ESE function in which the SRm160/300 splicing coactivator promotes critical interactions between ESE-bound "activators" and the snRNP machinery of the spliceosome. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005515 protein binding | IPI PMID:17332742 Composition and three-dimensional EM structure of double aff... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a splicing factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: splicing factor binding |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a splicing factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: splicing factor binding |
| GO:0005515 protein binding | IPI PMID:22365833 Dynamic protein-protein interaction wiring of the human spli... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a splicing factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: splicing factor binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a protein kinase partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: A proteome-scale binary-interaction map yields many partners, but bare protein binding is uninformative and the mixed partner set cannot be represented by one precise molecular-function term. Reason: Four partners in this collapsed tuple recur in independent splicing-factor or kinase interaction datasets and can be classified in those source-specific rows. The other eleven span heterogeneous molecular classes, so no single informative replacement represents the full HuRI set. The binary interactions remain available in the source database without a generic GO term that overstates their functional interpretation. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a protein kinase partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a protein kinase partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a splicing factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: splicing factor binding |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The HuRI-derived self-association is encoded by the IPI/WITH record, but the cached article does not expose the TRA2B-specific pair for direct verification. Reason: The interaction may be present in HuRI's underlying dataset, but the available text only describes the atlas globally. Keep the curated row undecided until the pair-level source data can be inspected rather than treating dataset-level evidence as positive support. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0032991 protein-containing complex | IDA PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | MODIFY | Summary: The experimental complex association is real but the generic protein-containing complex term does not identify the relevant RNA-processing assembly. Reason: TRA2B associates with splicing regulators and enhancer-dependent spliceosomal machinery. Spliceosomal complex is the more informative cellular-component term. Proposed replacements: spliceosomal complex Supporting Evidence: PMID:10339552 The results suggest a model for ESE function in which the SRm160/300 splicing coactivator promotes critical interactions between ESE-bound "activators" and the snRNP machinery of the spliceosome. |
| GO:0003723 RNA binding | IMP PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0005515 protein binding | IPI PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a splicing factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: splicing factor binding |
| GO:0005634 nucleus | IDA PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0019904 protein domain specific binding | IPI PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | KEEP AS NON CORE | Summary: Domain-specific association with an RNA-splicing regulator is experimentally supported but is a partner interaction rather than TRA2B's defining RNA-recognition activity. Reason: The term is informative and more specific than protein binding, but the core activity remains sequence-specific pre-mRNA recognition and regulation of exon selection. |
| GO:0042802 identical protein binding | IDA PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | UNDECIDED | Summary: The curated IDA self-association cannot be verified from the cached abstract, which reports TRA2B interactions with RBM-family proteins but does not mention TRA2B self-binding. Reason: The experimental curator may have used data in the unavailable full text, so the annotation is not removed or called wrong. It remains undecided until the self-association experiment can be inspected directly. |
| GO:0043484 regulation of RNA splicing | IMP PMID:10749975 RBMY, a probable human spermatogenesis factor, and other hnR... | MODIFY | Summary: The experiment establishes regulation of enhancer-dependent pre-mRNA splicing but does not restrict TRA2B's regulatory program to alternative target exons. Reason: Perturbing the RBM interaction domain inhibited splicing of a TRA2B-bound enhancer substrate. The spliceosome-specific regulatory parent captures this result and remains compatible with later evidence that TRA2 proteins control both constitutive and alternative target exons. Proposed replacements: regulation of mRNA splicing, via spliceosome Supporting Evidence: PMID:10749975 Incubation with the protein interaction domain of RBM inhibited splicing in vitro of a specific pre-mRNA substrate containing an essential enhancer bound by Tra2beta. |
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IMP PMID:25689357 Regulation of RAGE splicing by hnRNP A1 and Tra2Ξ²-1 and its ... | ACCEPT | Summary: Regulation of alternative mRNA splicing through the spliceosome is TRA2B's central biological process. Reason: Target-specific perturbation and biochemical studies show that TRA2B changes exon inclusion, with activating or repressive outcomes determined by target and partner context. |
| GO:0005681 spliceosomal complex | IMP PMID:25689357 Regulation of RAGE splicing by hnRNP A1 and Tra2Ξ²-1 and its ... | ACCEPT | Summary: Spliceosomal-complex association is consistent with phylogenetic, experimental, and pathway evidence and with TRA2B coupling enhancer-bound RNA to snRNP machinery. Reason: TRA2B functions in dynamic pre-mRNA processing assemblies, and independent mechanistic evidence connects ESE-bound TRA2 proteins to U1/U2 spliceosomal machinery. Supporting Evidence: PMID:10339552 The results suggest a model for ESE function in which the SRm160/300 splicing coactivator promotes critical interactions between ESE-bound "activators" and the snRNP machinery of the spliceosome. |
| GO:0036002 pre-mRNA binding | IDA PMID:25689357 Regulation of RAGE splicing by hnRNP A1 and Tra2Ξ²-1 and its ... | ACCEPT | Summary: Direct pre-mRNA binding is a core TRA2B activity and is supported by target-specific RNA-binding and splicing assays. Reason: The annotation is accurate. Structural work further resolves the activity as sequence-specific recognition of purine-rich pre-mRNA elements. Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0071333 cellular response to glucose stimulus | IMP PMID:25689357 Regulation of RAGE splicing by hnRNP A1 and Tra2Ξ²-1 and its ... | KEEP AS NON CORE | Summary: TRA2B abundance changes during glucose deprivation in the AGER/RAGE splicing experiment, but this is a condition-specific response rather than its core activity. Reason: The experimental observation is supported, yet it describes one regulatory context for TRA2B expression and downstream isoform balance, not the molecular role that defines TRA2B. Supporting Evidence: PMID:25689357 Glucose deprivation induced an increased ratio of mRAGE/esRAGE via up-regulation of hnRNP A1 and down-regulation of Tra2Ξ²-1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-72103 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770119 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770129 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770131 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770132 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770141 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770142 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770145 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770236 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770847 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9794542 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970141 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970179 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970189 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970190 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970191 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970193 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970282 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970294 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970318 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970320 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970428 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970429 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9970431 | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: The Reactome event is assigned to the nucleoplasm, matching direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005634 nucleus | HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp... | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0005515 protein binding | IPI PMID:12165565 hnRNP-G promotes exon 7 inclusion of survival motor neuron (... | MODIFY | Summary: Direct interactions with RBMY1A1 and RBMX are more informatively represented as splicing factor binding than as generic protein binding. Reason: The WITH/FROM partners P0DJD3 and P38159 are RBMY1A1 and RBMX, and the paper directly shows specific binding of hnRNP-G/RBM proteins to Htra2-beta1 in an exon-inclusion mechanism. Splicing factor binding preserves that informative partner class. Proposed replacements: splicing factor binding Supporting Evidence: PMID:12165565 hnRNP-G and RBM non-specifically bind RNA, but directly and specifically bind Htra2-beta1, an SR-like splicing factor which we have previously shown to stimulate inclusion of exon 7 through a direct interaction with the AG-rich ESE in SMN2 exon 7 pre-mRNA. |
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IDA PMID:12165565 hnRNP-G promotes exon 7 inclusion of survival motor neuron (... | ACCEPT | Summary: Regulation of alternative mRNA splicing through the spliceosome is TRA2B's central biological process. Reason: Target-specific perturbation and biochemical studies show that TRA2B changes exon inclusion, with activating or repressive outcomes determined by target and partner context. Supporting Evidence: PMID:12165565 hnRNP-G and RBM non-specifically bind RNA, but directly and specifically bind Htra2-beta1, an SR-like splicing factor which we have previously shown to stimulate inclusion of exon 7 through a direct interaction with the AG-rich ESE in SMN2 exon 7 pre-mRNA. |
| GO:0003729 mRNA binding | IDA PMID:12165565 hnRNP-G promotes exon 7 inclusion of survival motor neuron (... | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IDA PMID:12761049 HnRNP G and Tra2beta: opposite effects on splicing matched b... | ACCEPT | Summary: Regulation of alternative mRNA splicing through the spliceosome is TRA2B's central biological process. Reason: Target-specific perturbation and biochemical studies show that TRA2B changes exon inclusion, with activating or repressive outcomes determined by target and partner context. Supporting Evidence: PMID:12761049 We show here that hnRNP G and hTra2beta have opposite effects upon the incorporation of several exons, both being able to act as either an activator or a repressor. |
| GO:0003729 mRNA binding | IDA PMID:12761049 HnRNP G and Tra2beta: opposite effects on splicing matched b... | MODIFY | Summary: The annotation captures TRA2B RNA recognition but is less specific than the established sequence-selective activity of its RNA-recognition motif. Reason: Biochemical and structural studies show direct recognition of AGAA/GAA-rich and structured CAA elements in pre-mRNAs. Sequence-specific mRNA binding is therefore more informative than generic nucleic acid, RNA, or mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0048026 positive regulation of mRNA splicing, via spliceosome | IDA PMID:15009664 Tau exon 10, whose missplicing causes frontotemporal dementi... | ACCEPT | Summary: Positive regulation of spliceosomal mRNA splicing is supported for MAPT exon 10 and other enhancer-dependent targets. Reason: The cached abstract for the original paper does not name TRA2B, so the curator's full-text assessment is retained and independently corroborated by direct TRA2B binding and RNA-interference studies on the same MAPT enhancer. Supporting Evidence: PMID:12649279 The interaction between Tra2 beta and the exonic splicing enhancer correlates with the activity of this enhancer element in stimulating splicing. PMID:16308321 Small interfering RNA-mediated suppression of endogenous SF2/ASF and Tra2beta significantly reduces exon 10 splicing. |
| GO:0005515 protein binding | IPI PMID:19282290 Heterogeneous nuclear ribonucleoprotein G regulates splice s... | MODIFY | Summary: The WITH/FROM accession P84586 resolves to rat Rbmxrtl, an hnRNP G retrogene-like pre-mRNA splicing regulator, so the interaction is more informative than generic protein binding. Reason: The source paper characterizes hnRNP G-family proteins as supraspliceosomal regulators of alternative splice-site selection. Splicing factor binding therefore records the verified partner class while remaining secondary to TRA2B's RNA-binding activity. Proposed replacements: splicing factor binding Supporting Evidence: PMID:19282290 hnRNP G is part of the supraspliceosome, where it regulates alternative splice site selection in a concentration-dependent manner. |
| GO:0005515 protein binding | IPI PMID:17577209 The interactome of the histone gene regulatory factor HiNF-P... | MODIFY | Summary: The reported physical association is better described by the molecular class of the identified partner than by generic protein binding. Reason: The GOA WITH/FROM identifier records a DNA-binding transcription factor partner. Replacing protein binding preserves the interaction evidence while making the annotation biologically informative; it remains secondary to TRA2B's RNA-binding splicing-regulatory activity. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:15169763 Distinct sequence motifs within the 68-kDa subunit of cleava... | MODIFY | Summary: CPSF6/CFIm68 binds TRA2B through a defined C-terminal alternating-charge domain, making domain-specific binding more informative than generic protein binding. Reason: PMID:15169763 maps the hTra2beta interaction specifically to the C-terminal alternating-charge domain of CFIm68. GO:0019904 captures that experimentally localized interface without elevating this secondary partner interaction to a core TRA2B function. Proposed replacements: protein domain specific binding Supporting Evidence: PMID:15169763 CF I(m)68 interacts with SRp20, 9G8, and hTra2beta, members of the SR family of splicing factors, via its C-terminal alternating charge domain. |
| GO:0000375 RNA splicing, via transesterification reactions | TAS PMID:9546399 Human Tra2 proteins are sequence-specific activators of pre-... | MODIFY | Summary: TRA2B regulates spliceosomal exon choice rather than catalysing constitutive pre-mRNA splicing. Reason: The founding biochemical study explicitly found no constitutive-splicing activity and instead demonstrated sequence-specific activation of enhancer-dependent splicing. The regulatory alternative-splicing term captures the activity without implying that TRA2B performs the core transesterification reaction. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:9546399 Neither Tra2 protein functioned in constitutive splicing in vitro, but both activated enhancer-dependent splicing in a sequence-specific manner and restored it after inhibition with competitor RNA. |
| GO:0000398 mRNA splicing, via spliceosome | IDA PMID:9546399 Human Tra2 proteins are sequence-specific activators of pre-... | MODIFY | Summary: TRA2B regulates spliceosomal exon choice rather than catalysing constitutive pre-mRNA splicing. Reason: The founding biochemical study explicitly found no constitutive-splicing activity and instead demonstrated sequence-specific activation of enhancer-dependent splicing. The regulatory alternative-splicing term captures the activity without implying that TRA2B performs the core transesterification reaction. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:9546399 Neither Tra2 protein functioned in constitutive splicing in vitro, but both activated enhancer-dependent splicing in a sequence-specific manner and restored it after inhibition with competitor RNA. |
| GO:0005634 nucleus | IDA PMID:9546399 Human Tra2 proteins are sequence-specific activators of pre-... | ACCEPT | Summary: Nuclear or nucleoplasmic localization is appropriate for a sequence-specific pre-mRNA splicing regulator. Reason: This localization agrees with direct microscopy showing nuclear TRA2B in SC35-positive speckles. The localization is a core setting for its RNA-splicing activity. Supporting Evidence: PMID:9212162 htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. |
| GO:1990825 sequence-specific mRNA binding | IDA PMID:21399644 Molecular basis of purine-rich RNA recognition by the human ... | NEW | Summary: Direct structural and mutational evidence establishes sequence-specific recognition of an AGAA element by the TRA2B RNA-recognition motif. Reason: GOA contains only broader RNA- and mRNA-binding terms. This term captures the experimentally demonstrated molecular specificity and is the best representation of TRA2B's core molecular function. Supporting Evidence: PMID:21399644 The central 5'-AGAA-3' motif is specifically recognized by residues from the Ξ²-sheet of the RRM and by residues from both extremities flanking the RRM. |
| GO:0048025 negative regulation of mRNA splicing, via spliceosome | IDA PMID:12761049 HnRNP G and Tra2beta: opposite effects on splicing matched b... | NEW | Summary: TRA2B can repress exon incorporation as well as activate it, depending on the exon and cellular context. Reason: Existing GOA records the general and positive regulatory activities but omits the directly demonstrated repressive direction. The paper reports several exons for which hTra2beta acts as a repressor. Supporting Evidence: PMID:12761049 We show here that hnRNP G and hTra2beta have opposite effects upon the incorporation of several exons, both being able to act as either an activator or a repressor. |
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Download this section (compressed HTML)Q: Which endogenous exons require TRA2B specifically, rather than redundant TRA2A/TRA2B activity, across human cell types and physiological expression ranges?
Q: Which positional RNA-binding, local sequence, partner, and phosphorylation features determine whether TRA2B promotes or represses exon inclusion?
Q: Are the short TRA2B isoform 2 and N-terminally truncated isoform 3 stable endogenous products with distinct RNA targets or regulatory activities?
Experiment: Introduce rapid endogenous degrons for TRA2B and TRA2A in several differentiated human cell types and compare acute single and joint depletion by TRA2B/TRA2A eCLIP and short- plus long-read RNA sequencing. Rescue from a matched locus with wild-type TRA2B or an RRM RNA-contact-defective mutant, and classify as direct targets only events with nearby binding and wild-type-specific rescue.
Hypothesis: TRA2B has both paralog-redundant and cell-type-specific direct splicing targets that are masked by TRA2A compensation.
Type: Acute degron perturbation, eCLIP, and RNA sequencing
Experiment: Test a massively parallel minigene library varying AGAA/GAA and structured CAA elements, their position relative to splice sites, and adjacent regulator motifs under titrated TRA2B expression and perturbation of TRA2A, RBMX, SR proteins, CLK kinases, and SRPK kinases. Validate predictive sequence features by base editing representative endogenous exons.
Hypothesis: Motif position, local RNA architecture, partner abundance, and RS-domain phosphorylation determine whether TRA2B activates or represses exon inclusion.
Type: Massively parallel splicing reporter and endogenous base editing
Experiment: Establish endogenous expression of each isoform by long-read RNA sequencing and targeted proteomics, then perform matched single-copy isoform rescue in an acute TRA2B-depletion background. Compare nuclear localization, eCLIP profiles, protein interactomes, and rescue of direct splicing events.
Hypothesis: TRA2B isoform 3 retains RNA binding but has altered partner recruitment, whereas isoform 2 is unstable or lacks splicing-regulatory activity.
Type: Isoform-resolved proteomics, eCLIP, and functional rescue
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